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Report for Clinical Trial NCT02311998

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Phase I/II Study of Bosutinib in Combination With Inotuzumab Ozogamicin in CD22-Positive Philadelphia-Chromosome Positive Acute Lymphoblastic Leukemia and Chronic Myeloid Leukemia Lymphoid Blast Phase

This phase I/II trial studies the side effects and best dose of bosutinib when given together with inotuzumab ozogamicin and to see how well it works in treating patients with acute lymphoblastic leukemia or chronic myeloid leukemia that has come back or does not respond to treatment. Bosutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotoxins, such as inotuzumab ozogamicin, are antibodies linked to a toxic substance and may help find cancer cells that express CD22 and kill them without harming normal cells. Giving bosutinib together with inotuzumab ozogamicin may be a better treatment for acute lymphoblastic leukemia or chronic myeloid leukemia.

NCT02311998 B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1 Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive Blasts More Than 5 Percent of Bone Marrow Nucleated Cells CD22 Positive Philadelphia Chromosome Positive, BCR-ABL1 Positive Chronic Myelogenous Leukemia Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive Refractory Chronic Myelogenous Leukemia, BCR-ABL1 Positive
MeSH:Leukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Blast Crisis Philadelphia Chromosome
HPO:Chronic myelogenous leukemia Leukemia Lymphoid leukemia Myeloid leukemia

3 Interventions

Name: Bosutinib

Description: Given PO
Type: Drug
Group Labels: 1

Treatment (bosutinib, inotuzumab ozogamicin)

Name: Inotuzumab Ozogamicin

Description: Given IV
Type: Biological
Group Labels: 1

Treatment (bosutinib, inotuzumab ozogamicin)

Name: Laboratory Biomarker Analysis

Description: Correlative studies
Type: Other
Group Labels: 1

Treatment (bosutinib, inotuzumab ozogamicin)


Primary Outcomes

Description: Will be observed.

Measure: Maximum tolerated dose of bosutinib defined as the highest dose level in which < 2 patients of 6 develop first course dose limiting toxicity (Phase I)

Time: At day 28

Description: The response will be evaluated along with its 95% confidence interval.

Measure: Major hematologic response for relapsed Philadelphia positive acute lymphoblastic leukemia (MaHR) (Phase II)

Time: Up to 16 weeks (cycle 4 of treatment)

Description: Will be observed.

Measure: Complete response/complete response with incomplete bone marrow recovery for newly diagnosed Philadelphia positive acute lymphoblastic leukemia or chronic myeloid leukemia or chronic myeloid leukemia- lymphoid blast phase with age >= 60 (Phase II)

Time: Up to 1 year after completion of study treatment

Secondary Outcomes

Description: Will be observed.

Measure: Overall major hematologic response (Phase I)

Time: Up to 1 year after completion of study treatment

Description: Estimated using the method of Kaplan-Meier. Cox regression models will be used to determine the relationship with the time-to-events and the potential prognostic factors.

Measure: Duration of response (Phase I)

Time: Up to 1 year after completion of study treatment

Description: Estimated using the method of Kaplan-Meier. Cox regression models will be used to determine the relationship with the time-to-events (e.g., OS) and the potential prognostic factors.

Measure: Overall survival (OS) (Phase I)

Time: Up to 1 year after completion of study treatment

Description: Safety data will be summarized by category, severity and frequency.

Measure: Incidence and severity of adverse events graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (Phase II)

Time: Up to 1 year after completion of study treatment

Description: Estimated using the method of Kaplan-Meier. Cox regression models will be used to determine the relationship with the time-to-events and the potential prognostic factors.

Measure: Duration of response (Phase II)

Time: Up to 1 year after completion of study treatment

Description: Estimated using the method of Kaplan-Meier. Cox regression models will be used to determine the relationship with the time-to-events (e.g., OS) and the potential prognostic factors.

Measure: Overall survival (Phase II)

Time: Up to 1 year after completion of study treatment

Purpose: Treatment

Allocation: N/A

Single Group Assignment


There is one SNP

SNPs


1 T315I

Cox regression models will be used to determine the relationship with the time-to-events (e.g., OS) and the potential prognostic factors.. Inclusion Criteria: - Relapsed or refractory B-cell ALL or CML in lymphoid blast phase; Philadelphia chromosome must be present at screening (as determined by cytogenetic analysis, fluorescence in situ hybridization [FISH], or polymerase chain reaction [PCR] [i.e., BCR-ABL positive]); Note: patients with CML who have received treatment with tyrosine kinase inhibitors for their CML, and have progressed to lymphoid blast phase are eligible for frontline treatment; Frontline Ph+ ALL or CML-lymphoid blast phase (LBC) Cohort: Patients with newly-diagnosed Ph+ ALL or CML-LBC, who have received no or minimal treatment (minimal treatment is defined as treatment with steroids/hydroxyurea of =< 2 week duration; vincristine =< 2 doses; tyrosine kinase inhibitor of =< 4 week duration; =< 2 doses of cytarabine) and are >= 60 years or older are eligible; patients must have bone marrow blasts > 5% at the time of screening - Expression of CD-22 in >= 20% blasts - Eastern Cooperative Oncology Group (ECOG) performance status score of < or = 2 - Serum bilirubin < or = 2.0 mg/dl - Serum creatinine < or = 2.0 mg/dl - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < or = 3 x upper limit of normal (ULN) - Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 30 days following the last dose of study drug; effective methods of birth control include: birth control pills, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin); intrauterine devices (IUDs); condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy - Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug - Patients or their legally authorized representative must provide written informed consent Exclusion Criteria: - History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years; patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses) - Patients with active unstable angina, concomitant clinically significant active arrhythmias, myocardial infarction within 6 months, or congestive heart failure New York Heart Association class III-IV; patients with a cardiac ejection fraction (as measured by either multi gated acquisition scan [MUGA] or echocardiogram) < 40% are excluded - Known evidence of active cerebral/meningeal disease; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease (defined as >= 2 consecutive spinal fluid assessments with no evidence of disease) at that time of registration - Previous treatment with any anti-CD22 directed therapy - Patients with previous allogeneic stem cell transplant (SCT) if they meet either of the following criteria: - < 100 days from allogeneic SCT - Active acute or chronic graft-versus-host disease (GvHD), or - Receiving immunosuppressive therapy as treatment for GvHD within the last 7 days - Patients with uncontrolled active infections (viral, bacterial, or fungal) are not eligible - Active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV) - Patients with liver cirrhosis or other serious active liver disease or with suspected alcohol abuse - History of autoimmune diseases (such as systemic lupus erythematosus [SLE], Wegener's, Wegener's granulomatosis, polyarteritis nodosa); Note: Prior autoimmune diseases are allowed as long as clinically stable - Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exceptions: - To reduce the circulating lymphoblast count or palliation: steroids, hydroxyurea; no washout necessary for these agents - For ALL maintenance/CML treatment: mercaptopurine, methotrexate, vincristine, single-agent, single-dose of cytarabine and/or tyrosine kinase inhibitors; these agents should be discontinued at least 48 hours prior to start of study drugs; (Note: the interval of time from last dose of any approved tyrosine kinase inhibitor [TKI] to start of protocol treatment is 48 hours regardless of the indication for treatment with the TKI) - Patients who have not recovered from acute non hematologic toxicity (to =< grade 1) of all previous therapy prior to enrollment - Females who are pregnant or lactating - Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study - Patients previously exposed to bosutinib are eligible unless they carry T315I - Patients with T315I mutations will be excluded (this criteria is not applicable for the frontline Ph+ ALL or CML-LBC cohort) Inclusion Criteria: - Relapsed or refractory B-cell ALL or CML in lymphoid blast phase; Philadelphia chromosome must be present at screening (as determined by cytogenetic analysis, fluorescence in situ hybridization [FISH], or polymerase chain reaction [PCR] [i.e., BCR-ABL positive]); Note: patients with CML who have received treatment with tyrosine kinase inhibitors for their CML, and have progressed to lymphoid blast phase are eligible for frontline treatment; Frontline Ph+ ALL or CML-lymphoid blast phase (LBC) Cohort: Patients with newly-diagnosed Ph+ ALL or CML-LBC, who have received no or minimal treatment (minimal treatment is defined as treatment with steroids/hydroxyurea of =< 2 week duration; vincristine =< 2 doses; tyrosine kinase inhibitor of =< 4 week duration; =< 2 doses of cytarabine) and are >= 60 years or older are eligible; patients must have bone marrow blasts > 5% at the time of screening - Expression of CD-22 in >= 20% blasts - Eastern Cooperative Oncology Group (ECOG) performance status score of < or = 2 - Serum bilirubin < or = 2.0 mg/dl - Serum creatinine < or = 2.0 mg/dl - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < or = 3 x upper limit of normal (ULN) - Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 30 days following the last dose of study drug; effective methods of birth control include: birth control pills, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin); intrauterine devices (IUDs); condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy - Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug - Patients or their legally authorized representative must provide written informed consent Exclusion Criteria: - History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years; patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses) - Patients with active unstable angina, concomitant clinically significant active arrhythmias, myocardial infarction within 6 months, or congestive heart failure New York Heart Association class III-IV; patients with a cardiac ejection fraction (as measured by either multi gated acquisition scan [MUGA] or echocardiogram) < 40% are excluded - Known evidence of active cerebral/meningeal disease; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease (defined as >= 2 consecutive spinal fluid assessments with no evidence of disease) at that time of registration - Previous treatment with any anti-CD22 directed therapy - Patients with previous allogeneic stem cell transplant (SCT) if they meet either of the following criteria: - < 100 days from allogeneic SCT - Active acute or chronic graft-versus-host disease (GvHD), or - Receiving immunosuppressive therapy as treatment for GvHD within the last 7 days - Patients with uncontrolled active infections (viral, bacterial, or fungal) are not eligible - Active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV) - Patients with liver cirrhosis or other serious active liver disease or with suspected alcohol abuse - History of autoimmune diseases (such as systemic lupus erythematosus [SLE], Wegener's, Wegener's granulomatosis, polyarteritis nodosa); Note: Prior autoimmune diseases are allowed as long as clinically stable - Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exceptions: - To reduce the circulating lymphoblast count or palliation: steroids, hydroxyurea; no washout necessary for these agents - For ALL maintenance/CML treatment: mercaptopurine, methotrexate, vincristine, single-agent, single-dose of cytarabine and/or tyrosine kinase inhibitors; these agents should be discontinued at least 48 hours prior to start of study drugs; (Note: the interval of time from last dose of any approved tyrosine kinase inhibitor [TKI] to start of protocol treatment is 48 hours regardless of the indication for treatment with the TKI) - Patients who have not recovered from acute non hematologic toxicity (to =< grade 1) of all previous therapy prior to enrollment - Females who are pregnant or lactating - Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study - Patients previously exposed to bosutinib are eligible unless they carry T315I - Patients with T315I mutations will be excluded (this criteria is not applicable for the frontline Ph+ ALL or CML-LBC cohort) B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); --- T315I ---

Cox regression models will be used to determine the relationship with the time-to-events (e.g., OS) and the potential prognostic factors.. Inclusion Criteria: - Relapsed or refractory B-cell ALL or CML in lymphoid blast phase; Philadelphia chromosome must be present at screening (as determined by cytogenetic analysis, fluorescence in situ hybridization [FISH], or polymerase chain reaction [PCR] [i.e., BCR-ABL positive]); Note: patients with CML who have received treatment with tyrosine kinase inhibitors for their CML, and have progressed to lymphoid blast phase are eligible for frontline treatment; Frontline Ph+ ALL or CML-lymphoid blast phase (LBC) Cohort: Patients with newly-diagnosed Ph+ ALL or CML-LBC, who have received no or minimal treatment (minimal treatment is defined as treatment with steroids/hydroxyurea of =< 2 week duration; vincristine =< 2 doses; tyrosine kinase inhibitor of =< 4 week duration; =< 2 doses of cytarabine) and are >= 60 years or older are eligible; patients must have bone marrow blasts > 5% at the time of screening - Expression of CD-22 in >= 20% blasts - Eastern Cooperative Oncology Group (ECOG) performance status score of < or = 2 - Serum bilirubin < or = 2.0 mg/dl - Serum creatinine < or = 2.0 mg/dl - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < or = 3 x upper limit of normal (ULN) - Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 30 days following the last dose of study drug; effective methods of birth control include: birth control pills, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin); intrauterine devices (IUDs); condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy - Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug - Patients or their legally authorized representative must provide written informed consent Exclusion Criteria: - History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years; patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses) - Patients with active unstable angina, concomitant clinically significant active arrhythmias, myocardial infarction within 6 months, or congestive heart failure New York Heart Association class III-IV; patients with a cardiac ejection fraction (as measured by either multi gated acquisition scan [MUGA] or echocardiogram) < 40% are excluded - Known evidence of active cerebral/meningeal disease; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease (defined as >= 2 consecutive spinal fluid assessments with no evidence of disease) at that time of registration - Previous treatment with any anti-CD22 directed therapy - Patients with previous allogeneic stem cell transplant (SCT) if they meet either of the following criteria: - < 100 days from allogeneic SCT - Active acute or chronic graft-versus-host disease (GvHD), or - Receiving immunosuppressive therapy as treatment for GvHD within the last 7 days - Patients with uncontrolled active infections (viral, bacterial, or fungal) are not eligible - Active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV) - Patients with liver cirrhosis or other serious active liver disease or with suspected alcohol abuse - History of autoimmune diseases (such as systemic lupus erythematosus [SLE], Wegener's, Wegener's granulomatosis, polyarteritis nodosa); Note: Prior autoimmune diseases are allowed as long as clinically stable - Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exceptions: - To reduce the circulating lymphoblast count or palliation: steroids, hydroxyurea; no washout necessary for these agents - For ALL maintenance/CML treatment: mercaptopurine, methotrexate, vincristine, single-agent, single-dose of cytarabine and/or tyrosine kinase inhibitors; these agents should be discontinued at least 48 hours prior to start of study drugs; (Note: the interval of time from last dose of any approved tyrosine kinase inhibitor [TKI] to start of protocol treatment is 48 hours regardless of the indication for treatment with the TKI) - Patients who have not recovered from acute non hematologic toxicity (to =< grade 1) of all previous therapy prior to enrollment - Females who are pregnant or lactating - Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study - Patients previously exposed to bosutinib are eligible unless they carry T315I - Patients with T315I mutations will be excluded (this criteria is not applicable for the frontline Ph+ ALL or CML-LBC cohort) Inclusion Criteria: - Relapsed or refractory B-cell ALL or CML in lymphoid blast phase; Philadelphia chromosome must be present at screening (as determined by cytogenetic analysis, fluorescence in situ hybridization [FISH], or polymerase chain reaction [PCR] [i.e., BCR-ABL positive]); Note: patients with CML who have received treatment with tyrosine kinase inhibitors for their CML, and have progressed to lymphoid blast phase are eligible for frontline treatment; Frontline Ph+ ALL or CML-lymphoid blast phase (LBC) Cohort: Patients with newly-diagnosed Ph+ ALL or CML-LBC, who have received no or minimal treatment (minimal treatment is defined as treatment with steroids/hydroxyurea of =< 2 week duration; vincristine =< 2 doses; tyrosine kinase inhibitor of =< 4 week duration; =< 2 doses of cytarabine) and are >= 60 years or older are eligible; patients must have bone marrow blasts > 5% at the time of screening - Expression of CD-22 in >= 20% blasts - Eastern Cooperative Oncology Group (ECOG) performance status score of < or = 2 - Serum bilirubin < or = 2.0 mg/dl - Serum creatinine < or = 2.0 mg/dl - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < or = 3 x upper limit of normal (ULN) - Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 30 days following the last dose of study drug; effective methods of birth control include: birth control pills, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin); intrauterine devices (IUDs); condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy - Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug - Patients or their legally authorized representative must provide written informed consent Exclusion Criteria: - History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years; patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses) - Patients with active unstable angina, concomitant clinically significant active arrhythmias, myocardial infarction within 6 months, or congestive heart failure New York Heart Association class III-IV; patients with a cardiac ejection fraction (as measured by either multi gated acquisition scan [MUGA] or echocardiogram) < 40% are excluded - Known evidence of active cerebral/meningeal disease; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease (defined as >= 2 consecutive spinal fluid assessments with no evidence of disease) at that time of registration - Previous treatment with any anti-CD22 directed therapy - Patients with previous allogeneic stem cell transplant (SCT) if they meet either of the following criteria: - < 100 days from allogeneic SCT - Active acute or chronic graft-versus-host disease (GvHD), or - Receiving immunosuppressive therapy as treatment for GvHD within the last 7 days - Patients with uncontrolled active infections (viral, bacterial, or fungal) are not eligible - Active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV) - Patients with liver cirrhosis or other serious active liver disease or with suspected alcohol abuse - History of autoimmune diseases (such as systemic lupus erythematosus [SLE], Wegener's, Wegener's granulomatosis, polyarteritis nodosa); Note: Prior autoimmune diseases are allowed as long as clinically stable - Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exceptions: - To reduce the circulating lymphoblast count or palliation: steroids, hydroxyurea; no washout necessary for these agents - For ALL maintenance/CML treatment: mercaptopurine, methotrexate, vincristine, single-agent, single-dose of cytarabine and/or tyrosine kinase inhibitors; these agents should be discontinued at least 48 hours prior to start of study drugs; (Note: the interval of time from last dose of any approved tyrosine kinase inhibitor [TKI] to start of protocol treatment is 48 hours regardless of the indication for treatment with the TKI) - Patients who have not recovered from acute non hematologic toxicity (to =< grade 1) of all previous therapy prior to enrollment - Females who are pregnant or lactating - Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study - Patients previously exposed to bosutinib are eligible unless they carry T315I - Patients with T315I mutations will be excluded (this criteria is not applicable for the frontline Ph+ ALL or CML-LBC cohort) B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); --- T315I --- --- T315I ---

Cox regression models will be used to determine the relationship with the time-to-events (e.g., OS) and the potential prognostic factors.. Inclusion Criteria: - Relapsed or refractory B-cell ALL or CML in lymphoid blast phase; Philadelphia chromosome must be present at screening (as determined by cytogenetic analysis, fluorescence in situ hybridization [FISH], or polymerase chain reaction [PCR] [i.e., BCR-ABL positive]); Note: patients with CML who have received treatment with tyrosine kinase inhibitors for their CML, and have progressed to lymphoid blast phase are eligible for frontline treatment; Frontline Ph+ ALL or CML-lymphoid blast phase (LBC) Cohort: Patients with newly-diagnosed Ph+ ALL or CML-LBC, who have received no or minimal treatment (minimal treatment is defined as treatment with steroids/hydroxyurea of =< 2 week duration; vincristine =< 2 doses; tyrosine kinase inhibitor of =< 4 week duration; =< 2 doses of cytarabine) and are >= 60 years or older are eligible; patients must have bone marrow blasts > 5% at the time of screening - Expression of CD-22 in >= 20% blasts - Eastern Cooperative Oncology Group (ECOG) performance status score of < or = 2 - Serum bilirubin < or = 2.0 mg/dl - Serum creatinine < or = 2.0 mg/dl - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < or = 3 x upper limit of normal (ULN) - Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 30 days following the last dose of study drug; effective methods of birth control include: birth control pills, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin); intrauterine devices (IUDs); condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy - Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug - Patients or their legally authorized representative must provide written informed consent Exclusion Criteria: - History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years; patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses) - Patients with active unstable angina, concomitant clinically significant active arrhythmias, myocardial infarction within 6 months, or congestive heart failure New York Heart Association class III-IV; patients with a cardiac ejection fraction (as measured by either multi gated acquisition scan [MUGA] or echocardiogram) < 40% are excluded - Known evidence of active cerebral/meningeal disease; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease (defined as >= 2 consecutive spinal fluid assessments with no evidence of disease) at that time of registration - Previous treatment with any anti-CD22 directed therapy - Patients with previous allogeneic stem cell transplant (SCT) if they meet either of the following criteria: - < 100 days from allogeneic SCT - Active acute or chronic graft-versus-host disease (GvHD), or - Receiving immunosuppressive therapy as treatment for GvHD within the last 7 days - Patients with uncontrolled active infections (viral, bacterial, or fungal) are not eligible - Active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV) - Patients with liver cirrhosis or other serious active liver disease or with suspected alcohol abuse - History of autoimmune diseases (such as systemic lupus erythematosus [SLE], Wegener's, Wegener's granulomatosis, polyarteritis nodosa); Note: Prior autoimmune diseases are allowed as long as clinically stable - Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exceptions: - To reduce the circulating lymphoblast count or palliation: steroids, hydroxyurea; no washout necessary for these agents - For ALL maintenance/CML treatment: mercaptopurine, methotrexate, vincristine, single-agent, single-dose of cytarabine and/or tyrosine kinase inhibitors; these agents should be discontinued at least 48 hours prior to start of study drugs; (Note: the interval of time from last dose of any approved tyrosine kinase inhibitor [TKI] to start of protocol treatment is 48 hours regardless of the indication for treatment with the TKI) - Patients who have not recovered from acute non hematologic toxicity (to =< grade 1) of all previous therapy prior to enrollment - Females who are pregnant or lactating - Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study - Patients previously exposed to bosutinib are eligible unless they carry T315I - Patients with T315I mutations will be excluded (this criteria is not applicable for the frontline Ph+ ALL or CML-LBC cohort) Inclusion Criteria: - Relapsed or refractory B-cell ALL or CML in lymphoid blast phase; Philadelphia chromosome must be present at screening (as determined by cytogenetic analysis, fluorescence in situ hybridization [FISH], or polymerase chain reaction [PCR] [i.e., BCR-ABL positive]); Note: patients with CML who have received treatment with tyrosine kinase inhibitors for their CML, and have progressed to lymphoid blast phase are eligible for frontline treatment; Frontline Ph+ ALL or CML-lymphoid blast phase (LBC) Cohort: Patients with newly-diagnosed Ph+ ALL or CML-LBC, who have received no or minimal treatment (minimal treatment is defined as treatment with steroids/hydroxyurea of =< 2 week duration; vincristine =< 2 doses; tyrosine kinase inhibitor of =< 4 week duration; =< 2 doses of cytarabine) and are >= 60 years or older are eligible; patients must have bone marrow blasts > 5% at the time of screening - Expression of CD-22 in >= 20% blasts - Eastern Cooperative Oncology Group (ECOG) performance status score of < or = 2 - Serum bilirubin < or = 2.0 mg/dl - Serum creatinine < or = 2.0 mg/dl - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < or = 3 x upper limit of normal (ULN) - Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 30 days following the last dose of study drug; effective methods of birth control include: birth control pills, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin); intrauterine devices (IUDs); condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy - Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug - Patients or their legally authorized representative must provide written informed consent Exclusion Criteria: - History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years; patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses) - Patients with active unstable angina, concomitant clinically significant active arrhythmias, myocardial infarction within 6 months, or congestive heart failure New York Heart Association class III-IV; patients with a cardiac ejection fraction (as measured by either multi gated acquisition scan [MUGA] or echocardiogram) < 40% are excluded - Known evidence of active cerebral/meningeal disease; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease (defined as >= 2 consecutive spinal fluid assessments with no evidence of disease) at that time of registration - Previous treatment with any anti-CD22 directed therapy - Patients with previous allogeneic stem cell transplant (SCT) if they meet either of the following criteria: - < 100 days from allogeneic SCT - Active acute or chronic graft-versus-host disease (GvHD), or - Receiving immunosuppressive therapy as treatment for GvHD within the last 7 days - Patients with uncontrolled active infections (viral, bacterial, or fungal) are not eligible - Active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV) - Patients with liver cirrhosis or other serious active liver disease or with suspected alcohol abuse - History of autoimmune diseases (such as systemic lupus erythematosus [SLE], Wegener's, Wegener's granulomatosis, polyarteritis nodosa); Note: Prior autoimmune diseases are allowed as long as clinically stable - Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exceptions: - To reduce the circulating lymphoblast count or palliation: steroids, hydroxyurea; no washout necessary for these agents - For ALL maintenance/CML treatment: mercaptopurine, methotrexate, vincristine, single-agent, single-dose of cytarabine and/or tyrosine kinase inhibitors; these agents should be discontinued at least 48 hours prior to start of study drugs; (Note: the interval of time from last dose of any approved tyrosine kinase inhibitor [TKI] to start of protocol treatment is 48 hours regardless of the indication for treatment with the TKI) - Patients who have not recovered from acute non hematologic toxicity (to =< grade 1) of all previous therapy prior to enrollment - Females who are pregnant or lactating - Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study - Patients previously exposed to bosutinib are eligible unless they carry T315I - Patients with T315I mutations will be excluded (this criteria is not applicable for the frontline Ph+ ALL or CML-LBC cohort) B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); --- T315I --- --- T315I --- --- T315I ---

Cox regression models will be used to determine the relationship with the time-to-events (e.g., OS) and the potential prognostic factors.. Inclusion Criteria: - Relapsed or refractory B-cell ALL or CML in lymphoid blast phase; Philadelphia chromosome must be present at screening (as determined by cytogenetic analysis, fluorescence in situ hybridization [FISH], or polymerase chain reaction [PCR] [i.e., BCR-ABL positive]); Note: patients with CML who have received treatment with tyrosine kinase inhibitors for their CML, and have progressed to lymphoid blast phase are eligible for frontline treatment; Frontline Ph+ ALL or CML-lymphoid blast phase (LBC) Cohort: Patients with newly-diagnosed Ph+ ALL or CML-LBC, who have received no or minimal treatment (minimal treatment is defined as treatment with steroids/hydroxyurea of =< 2 week duration; vincristine =< 2 doses; tyrosine kinase inhibitor of =< 4 week duration; =< 2 doses of cytarabine) and are >= 60 years or older are eligible; patients must have bone marrow blasts > 5% at the time of screening - Expression of CD-22 in >= 20% blasts - Eastern Cooperative Oncology Group (ECOG) performance status score of < or = 2 - Serum bilirubin < or = 2.0 mg/dl - Serum creatinine < or = 2.0 mg/dl - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < or = 3 x upper limit of normal (ULN) - Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 30 days following the last dose of study drug; effective methods of birth control include: birth control pills, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin); intrauterine devices (IUDs); condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy - Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug - Patients or their legally authorized representative must provide written informed consent Exclusion Criteria: - History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years; patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses) - Patients with active unstable angina, concomitant clinically significant active arrhythmias, myocardial infarction within 6 months, or congestive heart failure New York Heart Association class III-IV; patients with a cardiac ejection fraction (as measured by either multi gated acquisition scan [MUGA] or echocardiogram) < 40% are excluded - Known evidence of active cerebral/meningeal disease; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease (defined as >= 2 consecutive spinal fluid assessments with no evidence of disease) at that time of registration - Previous treatment with any anti-CD22 directed therapy - Patients with previous allogeneic stem cell transplant (SCT) if they meet either of the following criteria: - < 100 days from allogeneic SCT - Active acute or chronic graft-versus-host disease (GvHD), or - Receiving immunosuppressive therapy as treatment for GvHD within the last 7 days - Patients with uncontrolled active infections (viral, bacterial, or fungal) are not eligible - Active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV) - Patients with liver cirrhosis or other serious active liver disease or with suspected alcohol abuse - History of autoimmune diseases (such as systemic lupus erythematosus [SLE], Wegener's, Wegener's granulomatosis, polyarteritis nodosa); Note: Prior autoimmune diseases are allowed as long as clinically stable - Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exceptions: - To reduce the circulating lymphoblast count or palliation: steroids, hydroxyurea; no washout necessary for these agents - For ALL maintenance/CML treatment: mercaptopurine, methotrexate, vincristine, single-agent, single-dose of cytarabine and/or tyrosine kinase inhibitors; these agents should be discontinued at least 48 hours prior to start of study drugs; (Note: the interval of time from last dose of any approved tyrosine kinase inhibitor [TKI] to start of protocol treatment is 48 hours regardless of the indication for treatment with the TKI) - Patients who have not recovered from acute non hematologic toxicity (to =< grade 1) of all previous therapy prior to enrollment - Females who are pregnant or lactating - Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study - Patients previously exposed to bosutinib are eligible unless they carry T315I - Patients with T315I mutations will be excluded (this criteria is not applicable for the frontline Ph+ ALL or CML-LBC cohort) Inclusion Criteria: - Relapsed or refractory B-cell ALL or CML in lymphoid blast phase; Philadelphia chromosome must be present at screening (as determined by cytogenetic analysis, fluorescence in situ hybridization [FISH], or polymerase chain reaction [PCR] [i.e., BCR-ABL positive]); Note: patients with CML who have received treatment with tyrosine kinase inhibitors for their CML, and have progressed to lymphoid blast phase are eligible for frontline treatment; Frontline Ph+ ALL or CML-lymphoid blast phase (LBC) Cohort: Patients with newly-diagnosed Ph+ ALL or CML-LBC, who have received no or minimal treatment (minimal treatment is defined as treatment with steroids/hydroxyurea of =< 2 week duration; vincristine =< 2 doses; tyrosine kinase inhibitor of =< 4 week duration; =< 2 doses of cytarabine) and are >= 60 years or older are eligible; patients must have bone marrow blasts > 5% at the time of screening - Expression of CD-22 in >= 20% blasts - Eastern Cooperative Oncology Group (ECOG) performance status score of < or = 2 - Serum bilirubin < or = 2.0 mg/dl - Serum creatinine < or = 2.0 mg/dl - Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) < or = 3 x upper limit of normal (ULN) - Females of childbearing potential must have a negative serum or urine beta human chorionic gonadotropin (beta-hCG) pregnancy test result within 14 days prior to the first dose of study drugs and must agree to use one of the following effective contraception methods during the study and for 30 days following the last dose of study drug; effective methods of birth control include: birth control pills, shots, implants (placed under the skin by a health care provider) or patches (placed on the skin); intrauterine devices (IUDs); condom or occlusive cap (diaphragm or cervical/vault caps) used with spermicide; females of non-childbearing potential are those who are postmenopausal greater than 1 year or who have had a bilateral tubal ligation or hysterectomy - Males who have partners of childbearing potential must agree to use an effective contraceptive method during the study and for 30 days following the last dose of study drug - Patients or their legally authorized representative must provide written informed consent Exclusion Criteria: - History of another primary invasive malignancy that has not been definitively treated or in remission for at least 2 years; patients with non-melanoma skin cancers or with carcinomas in situ are eligible regardless of the time from diagnosis (including concomitant diagnoses) - Patients with active unstable angina, concomitant clinically significant active arrhythmias, myocardial infarction within 6 months, or congestive heart failure New York Heart Association class III-IV; patients with a cardiac ejection fraction (as measured by either multi gated acquisition scan [MUGA] or echocardiogram) < 40% are excluded - Known evidence of active cerebral/meningeal disease; patients may have history of central nervous system (CNS) leukemic involvement if definitively treated with prior therapy and no evidence of active disease (defined as >= 2 consecutive spinal fluid assessments with no evidence of disease) at that time of registration - Previous treatment with any anti-CD22 directed therapy - Patients with previous allogeneic stem cell transplant (SCT) if they meet either of the following criteria: - < 100 days from allogeneic SCT - Active acute or chronic graft-versus-host disease (GvHD), or - Receiving immunosuppressive therapy as treatment for GvHD within the last 7 days - Patients with uncontrolled active infections (viral, bacterial, or fungal) are not eligible - Active hepatitis B or C infection, or known seropositivity for human immunodeficiency virus (HIV) - Patients with liver cirrhosis or other serious active liver disease or with suspected alcohol abuse - History of autoimmune diseases (such as systemic lupus erythematosus [SLE], Wegener's, Wegener's granulomatosis, polyarteritis nodosa); Note: Prior autoimmune diseases are allowed as long as clinically stable - Prior chemotherapy/radiotherapy/investigational therapy within 2 weeks before the start of study drugs with the following exceptions: - To reduce the circulating lymphoblast count or palliation: steroids, hydroxyurea; no washout necessary for these agents - For ALL maintenance/CML treatment: mercaptopurine, methotrexate, vincristine, single-agent, single-dose of cytarabine and/or tyrosine kinase inhibitors; these agents should be discontinued at least 48 hours prior to start of study drugs; (Note: the interval of time from last dose of any approved tyrosine kinase inhibitor [TKI] to start of protocol treatment is 48 hours regardless of the indication for treatment with the TKI) - Patients who have not recovered from acute non hematologic toxicity (to =< grade 1) of all previous therapy prior to enrollment - Females who are pregnant or lactating - Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that in the opinion of the investigator may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and/or would make the patient inappropriate for enrollment into this study - Patients previously exposed to bosutinib are eligible unless they carry T315I - Patients with T315I mutations will be excluded (this criteria is not applicable for the frontline Ph+ ALL or CML-LBC cohort) B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); --- T315I --- --- T315I --- --- T315I --- --- T315I ---



HPO Nodes


HPO: