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Report for Mutation P140K

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

There are 4 clinical trials

Clinical Trials


1 Benzylguanine-Mediated Tumor Sensitization With Chemoprotected Autologous Stem Cells for Patients With Malignant Gliomas

This phase I/II trial studies the side effects and best dose of temozolomide when given together with radiation therapy, carmustine, O6-benzylguanine, and patients' own stem cell (autologous) transplant in treating patients with newly diagnosed glioblastoma multiforme or gliosarcoma. Giving chemotherapy, such as temozolomide, carmustine, and O6-benzylguanine, and radiation therapy before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. Giving colony-stimulating factors, such as filgrastim or plerixafor, and certain chemotherapy drugs, helps stem cells move from the bone marrow to the blood so they can be collected and stored. Chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. The stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy.

NCT00669669 Glioblastoma Gliosarcoma Radiation: 3-Dimensional Conformal Radiation Therapy Procedure: Autologous Hematopoietic Stem Cell Transplantation Drug: Carmustine Biological: Filgrastim Procedure: In Vitro-Treated Peripheral Blood Stem Cell Transplantation Radiation: Intensity-Modulated Radiation Therapy Other: Laboratory Biomarker Analysis Drug: O6-Benzylguanine Drug: Plerixafor Radiation: Proton Beam Radiation Therapy Drug: Temozolomide
MeSH: Glioblastoma Glioma Gliosarcoma
HPO: Glioblastoma multiforme Glioma

Inclusion Criteria: - Patients with glioblastoma multiforme or gliosarcoma - The patient or legal guardian must be able to comprehend the informed consent form and sign prior to patient enrollment - Karnofsky performance status at time of study entry must be >= 70% - Life expectancy of >= 3 months - Patients must agree to undergo repeat clinical neurological examinations and brain magnetic resonance imaging (MRI) with appropriate contrast after every other cycle of chemotherapy - White blood cell (WBC) > 3000/ul - Absolute neutrophil count (ANC) > 1500/ul - Platelets > 100,000/ul - Hemoglobin > 10 gm/100ml - Total and direct bilirubin < 1.5 times upper limit of laboratory normal - Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 3 times upper limit of laboratory normal - Alkaline phosphatase =< 3 times upper limit of laboratory normal - Blood urea nitrogen (BUN) < 1.5 times upper limit of laboratory normal - Serum creatinine < 1.5 times upper limit of laboratory normal - Left ventricular ejection fraction (LVEF) >= 40%, however, subjects with a LVEF in the range of 40-49% should have cardiology clearance prior to intervention - MGMT promoter methylation analysis of surgically resected tumor or tumor biopsy must demonstrate an unmethylated or hypomethylated MGMT promoter status Exclusion Criteria: - Patients with cardiac insufficiency and a LVEF of < 40%; history of coronary artery disease or arrhythmia, which has required or requires ongoing treatment - Patients with active pulmonary infection and/or pulse oximetry < 90% and a corrected diffusion capacity of the lung for carbon monoxide (DLCO) < 70% of predicted - Active systemic infection - Patients who are human immunodeficiency virus (HIV) positive - Pregnant or lactating women; a beta-human chorionic gonadotropin (HCG) level will be obtained from women of childbearing potential; fertile men and women should use effective contraception - Previous chemotherapy for any malignancy including temozolomide, dacarbazine (DTIC) or prior nitrosourea - Diabetes mellitus - Bleeding disorder - Methylated or hypermethylated MGMT promoter status within tumor tissue - Medical or psychiatric condition which in the opinion of the protocol chairman would compromise the patient's ability to tolerate this protocol - Prior interstitial radiotherapy, stereotactic or gamma knife surgery or implanted BCNU-wafers Inclusion Criteria: - Patients with glioblastoma multiforme or gliosarcoma - The patient or legal guardian must be able to comprehend the informed consent form and sign prior to patient enrollment - Karnofsky performance status at time of study entry must be >= 70% - Life expectancy of >= 3 months - Patients must agree to undergo repeat clinical neurological examinations and brain magnetic resonance imaging (MRI) with appropriate contrast after every other cycle of chemotherapy - White blood cell (WBC) > 3000/ul - Absolute neutrophil count (ANC) > 1500/ul - Platelets > 100,000/ul - Hemoglobin > 10 gm/100ml - Total and direct bilirubin < 1.5 times upper limit of laboratory normal - Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 3 times upper limit of laboratory normal - Alkaline phosphatase =< 3 times upper limit of laboratory normal - Blood urea nitrogen (BUN) < 1.5 times upper limit of laboratory normal - Serum creatinine < 1.5 times upper limit of laboratory normal - Left ventricular ejection fraction (LVEF) >= 40%, however, subjects with a LVEF in the range of 40-49% should have cardiology clearance prior to intervention - MGMT promoter methylation analysis of surgically resected tumor or tumor biopsy must demonstrate an unmethylated or hypomethylated MGMT promoter status Exclusion Criteria: - Patients with cardiac insufficiency and a LVEF of < 40%; history of coronary artery disease or arrhythmia, which has required or requires ongoing treatment - Patients with active pulmonary infection and/or pulse oximetry < 90% and a corrected diffusion capacity of the lung for carbon monoxide (DLCO) < 70% of predicted - Active systemic infection - Patients who are human immunodeficiency virus (HIV) positive - Pregnant or lactating women; a beta-human chorionic gonadotropin (HCG) level will be obtained from women of childbearing potential; fertile men and women should use effective contraception - Previous chemotherapy for any malignancy including temozolomide, dacarbazine (DTIC) or prior nitrosourea - Diabetes mellitus - Bleeding disorder - Methylated or hypermethylated MGMT promoter status within tumor tissue - Medical or psychiatric condition which in the opinion of the protocol chairman would compromise the patient's ability to tolerate this protocol - Prior interstitial radiotherapy, stereotactic or gamma knife surgery or implanted BCNU-wafers Glioblastoma Gliosarcoma Glioblastoma Glioma Gliosarcoma PRIMARY OBJECTIVES: I. Determine the safety and feasibility of infusing autologous granulocyte colony-stimulating factor (G-CSF) (filgrastim) mobilized stem cells transduced with a Phoenix-gibbon ape leukemia virus (GALV)-pseudotype vector expressing methylguanine methyltransferase (MGMT) (P140K). --- P140K ---

V. Determine the correlation of the level of MGMT (P140K) marking with toxicity, temozolomide dose achieved, and response. --- P140K ---

Primary Outcomes

Description: Defined as any grade 4 nonhematopoietic toxicity that is likely related to the investigational procedures (Part I)

Measure: Number of Participants Dose-limiting Toxicity (DLT)

Time: Up to 6 weeks after infusion

Description: Replication competent retrovirus or diagnosis of leukemia

Measure: Number of Participants With Retrovirus or Leukemia

Time: Up to 2 years after infusion

Secondary Outcomes

Description: Proportion of patients with reduction in tumor burden of a predefined amount

Measure: Response Rate

Time: Up to 15 years

Description: From the onset of temozolomide to the date at which unequivocal disease progression, assessed up to 15 years

Measure: Duration of Response

Time: Up to 15 years

Description: From the first day of treatment until death, assessed up to 15 years

Measure: Number of Participants That Survived

Time: Up to 15 years

Description: From the first day of treatment until unequivocal progression is documented, assessed up to 15 years

Measure: Time to Progression

Time: Up to 15 years

Description: Assessed by gene marking in peripheral blood and marrow

Measure: Gene Transfer Efficiency and in Vivo Selection

Time: Up to 15 years

Description: assessed by the ability to increase the Temozolomide dose beyond 472 mg/m^2

Measure: Number of Participants With Chemoprotection

Time: Up to 15 years

2 06-benzylguanine (BG) and Temozolomide (TMZ) Therapy of Glioblastoma Multiforme (GBM) in Patients With MGMT Positive Tumors With Infusion of Autologous P140KMGMT+ Hematopoietic Progenitors to Protect Hematopoiesis

RATIONALE: Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. O6-benzylguanine may help temozolomide work better by making tumor cells more sensitive to the drug. Giving genetically modified peripheral blood stem cells during or after treatment may prevent side effects caused by chemotherapy. PURPOSE: This clinical trial studies O6-benzylguanine and temozolomide in combination with genetically modified peripheral blood stem cells in treating patients with newly diagnosed glioblastoma multiforme.

NCT01269424 Glioblastoma Multiforme Biological: MGMTP140K-encoding retroviral vector Drug: O6-benzylguanine Drug: temozolomide Other: laboratory biomarker analysis Procedure: autologous hematopoietic stem cell transplantation Procedure: in vitro-treated peripheral blood stem cell transplantation Radiation: radiation therapy
MeSH: Glioblastoma
HPO: Glioblastoma multiforme

Feasibility and safety of infusing autologous P140K MGMT-transduced hematopoietic progenitors into patients with GBM. --- P140K ---

Quantitate P140K transduced hematopoietic cells from the bone marrow and peripheral blood in patients infused with P140K transduced CD34 progenitors. --- P140K ---

Quantitate P140K transduced hematopoietic cells from the bone marrow and peripheral blood in patients infused with P140K transduced CD34 progenitors. --- P140K --- --- P140K ---

To evaluate the in vivo enrichment of P140K expressing hematopoietic cells by repeated treatments of BG and TMZ. --- P140K ---

- Prior diagnosis of malignant disease within a three year period with the exception of surgically cured basal cell carcinoma or carcinoma in situ of the cervix - Mental incapacity or psychiatric illness preventing informed consent Glioblastoma Multiforme Glioblastoma OBJECTIVES: Primary - To evaluate the feasibility of introducing and expressing P140K MGMT cDNA from a lentiviral-based provirus in autologous hematopoietic stem cells harvested from Glioblastoma multiforme (GBM) patients. --- P140K ---

- To assess the safety associated with infusion of autologous hematopoietic stem cells transduced ex vivo with a lentiviral vector expressing P140K MGMT in patients with GBM. --- P140K ---

Secondary - To determine whether any patients who receive P140K MGMT-transduced CD34 cells tolerate O6-benzylguanine (BG) and dose-escalated temozolomide (TMZ) without myelosuppression. --- P140K ---

- To evaluate the ability to detect P140K-transduced BG and TMZ-resistant hematopoietic cells from the bone marrow and peripheral blood in patients infused with P140K-transduced CD34 progenitors. --- P140K ---

- To evaluate the ability to detect P140K-transduced BG and TMZ-resistant hematopoietic cells from the bone marrow and peripheral blood in patients infused with P140K-transduced CD34 progenitors. --- P140K --- --- P140K ---

- To evaluate the feasibility of in vivo enrichment of P140K-expressing hematopoietic cells by repeated treatments of BG and TMZ at doses that appear therapeutic for GBM. - To evaluate the efficacy of various types of chemotherapy with or without radiotherapy on conditioning the patient's bone marrow to host the transduced autologous hematopoetic stem cells. --- P140K ---

- Cohort 1 (LV P140K MGMT gene transfer after concurrent chemoradiotherapy): Patients receive radiotherapy (60cGy in 30 2cGy daily doses) and TMZ 75mg/m2 /daily for 6 weeks, cell infusion at week 7 (T0) followed by BG 120 mg/m2 intravenous infusion over 1h and TMZ 50 mg/m2/day x 5 days, every 28 days (starting on T+28) for 6 cycles. --- P140K ---

- Cohort 2 (LV P140K MGMT gene transfer prior to concurrent chemoradiotherapy): Patients receive BG 120mg/m2 intravenous infusion over 1h and TMZ 400 mg/m2 one dose given on day T-2 or T-3 days prior to cell infusion, followed within 72-96 hours by radiotherapy (60cGy in 30 2cGy daily doses) and concurrent BG + TMZ at 50 mg/m2/day x 5 days, every 28 days,starting on T+28 for a total of 7 cycles of BG + TMZ. - Cohort 3 (intra-patient dose escalation of TMZ in patients with evidence of P140K-marked cells): Dose escalation of TMZ in patients with evidence of P140K marked cells in vivo given as described above for cohort 1 or cohort 2. After completion of radiotherapy, patients will receive BG + TMZ at 50 mg/m2/day x 5 days. --- P140K ---

- Cohort 2 (LV P140K MGMT gene transfer prior to concurrent chemoradiotherapy): Patients receive BG 120mg/m2 intravenous infusion over 1h and TMZ 400 mg/m2 one dose given on day T-2 or T-3 days prior to cell infusion, followed within 72-96 hours by radiotherapy (60cGy in 30 2cGy daily doses) and concurrent BG + TMZ at 50 mg/m2/day x 5 days, every 28 days,starting on T+28 for a total of 7 cycles of BG + TMZ. - Cohort 3 (intra-patient dose escalation of TMZ in patients with evidence of P140K-marked cells): Dose escalation of TMZ in patients with evidence of P140K marked cells in vivo given as described above for cohort 1 or cohort 2. After completion of radiotherapy, patients will receive BG + TMZ at 50 mg/m2/day x 5 days. --- P140K --- --- P140K ---

- Cohort 2 (LV P140K MGMT gene transfer prior to concurrent chemoradiotherapy): Patients receive BG 120mg/m2 intravenous infusion over 1h and TMZ 400 mg/m2 one dose given on day T-2 or T-3 days prior to cell infusion, followed within 72-96 hours by radiotherapy (60cGy in 30 2cGy daily doses) and concurrent BG + TMZ at 50 mg/m2/day x 5 days, every 28 days,starting on T+28 for a total of 7 cycles of BG + TMZ. - Cohort 3 (intra-patient dose escalation of TMZ in patients with evidence of P140K-marked cells): Dose escalation of TMZ in patients with evidence of P140K marked cells in vivo given as described above for cohort 1 or cohort 2. After completion of radiotherapy, patients will receive BG + TMZ at 50 mg/m2/day x 5 days. --- P140K --- --- P140K --- --- P140K ---

Primary Outcomes

Description: Patients will be assessed for clinical symptoms and side-effects - CTCAE v 4.0 - from time of treatment until protocol is stopped due to toxicity, progression, patient choice, or patient election to enroll on new therapeutic option.

Measure: Feasibility and safety of infusing autologous P140K MGMT-transduced hematopoietic progenitors into patients with GBM

Time: up to 5 years

Secondary Outcomes

Description: Quantitate P140K transduced hematopoietic cells from the bone marrow and peripheral blood in patients infused with P140K transduced CD34 progenitors

Measure: Successful transduction rate

Time: up to 4 years

Description: To evaluate the in vivo enrichment of P140K expressing hematopoietic cells by repeated treatments of BG and TMZ

Measure: To evaluate the in vivo enrichment of P140K expressing hematopoietic cells by repeated treatments of BG and TMZ

Time: up to 4 years

Description: Progression-free survival defined as the time interval between the date of initial histological diagnosis and the date of disease progression or death, whichever comes first

Measure: Progression-free

Time: up to 5 years

Description: New tumor or increased tumor size on T1WI + Gd of > 25% as measured by the sum of two perpendicular diameters compared to the smallest measurements ever recorded for the same lesion by the same technique.

Measure: Number of patients with radiological progression

Time: up to 5 years

Description: From the date of enrollment to death, last contact or last tumor assessment before further anti-tumor therapy, assessed up to 5 years.

Measure: Overall Survival

Time: up to 5 years

3 AUTOLOGOUS TRANSPLANTATION AND STEM CELL BASED-GENE THERAPY FOR THE TREATMENT OF HIV-ASSOCIATED LYMPHOMA

This clinical trial studies genetically modified peripheral blood stem cell transplant in treating patients with HIV-associated non-Hodgkin or Hodgkin lymphoma. Giving chemotherapy before a peripheral stem cell transplant stops the growth of cancer cells by stopping them from dividing or killing them. After treatment, stem cells are collected from the patient's blood and stored. More chemotherapy or radiation therapy is then given to prepare the bone marrow for the stem cell transplant. Laboratory-treated stem cells are then returned to the patient to replace the blood-forming cells that were destroyed by the chemotherapy and radiation therapy

NCT01769911 Adult Nasal Type Extranodal NK/T-cell Lymphoma AIDS-related Diffuse Large Cell Lymphoma AIDS-related Diffuse Mixed Cell Lymphoma AIDS-related Diffuse Small Cleaved Cell Lymphoma AIDS-related Immunoblastic Large Cell Lymphoma AIDS-related Lymphoblastic Lymphoma AIDS-related Peripheral/Systemic Lymphoma AIDS-related Small Noncleaved Cell Lymphoma Anaplastic Large Cell Lymphoma Angioimmunoblastic T-cell Lymphoma Cutaneous B-cell Non-Hodgkin Lymphoma Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue Hepatosplenic T-cell Lymphoma HIV-associated Hodgkin Lymphoma Intraocular Lymphoma Nodal Marginal Zone B-cell Lymphoma Noncutaneous Extranodal Lymphoma Peripheral T-cell Lymphoma Recurrent Adult Burkitt Lymphoma Recurrent Adult Diffuse Large Cell Lymphoma Recurrent Adult Diffuse Mixed Cell Lymphoma Recurrent Adult Diffuse Small Cleaved Cell Lymphoma Recurrent Adult Grade III Lymphomatoid Granulomatosis Recurrent Adult Hodgkin Lymphoma Recurrent Adult Immunoblastic Large Cell Lymphoma Recurrent Adult Lymphoblastic Lymphoma Recurrent Adult T-cell Leukemia/Lymphoma Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Mycosis Fungoides/Sezary Syndrome Recurrent Small Lymphocytic Lymphoma Refractory Hairy Cell Leukemia Small Intestine Lymphoma Splenic Marginal Zone Lymphoma Stage I AIDS-related Lymphoma Stage II AIDS-related Lymphoma Stage III AIDS-related Lymphoma Stage IV AIDS-related Lymphoma T-cell Large Granular Lymphocyte Leukemia Testicular Lymphoma Waldenström Macroglobulinemia Drug: carmustine Drug: cytarabine Drug: melphalan Drug: etoposide Drug: O6-benzylguanine Procedure: autologous hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Other: laboratory biomarker analysis
MeSH: Mycoses Burkitt Lymphoma Lymphoma Leukemia Lymphoma, Follicular Lymphoma, Non-Hodgkin Lymphoma, B-Cell Hodgkin Disease Lymphoma, Mantle-Cell Lymphoma, B-Cell, Marginal Zone Leukemia, Lymphocytic, Chronic, B-Cell Precurs Precursor Cell Lymphoblastic Leukemia-Lymphoma Lymphoma, Large B-Cell, Diffuse Lymphoma, T-Cell Lymphoma, Large-Cell, Immunoblastic Plasmablastic Lymphoma Mycosis Fungoides Sezary Syndrome Lymphoma, T-Cell, Cutaneous Leukemia, T-Cell Leukemia-Lymphoma, Adult T-Cell Waldenstrom Macroglobulinemia Lymphoma, Large-Cell, Anaplastic Lymphoma, T-Cell, Peripheral Leukemia, Hairy Cell Lymphomatoid Granulomatosis Lymphoma, Extranodal NK-T-Cell Intraocular Lymphoma Leukemia, Large Granular Lymphocytic Lymphoma, AIDS-Related Immunoblastic Lymphadenopathy
HPO: Anaplastic large-cell lymphoma B-cell lymphoma Burkitt lymphoma Chronic lymphatic leukemia Cutaneous T-cell lymphoma Hodgkin lymphoma Leukemia Lymphoma Monoclonal immunoglobulin M proteinemia Non-Hodgkin lymphoma T-cell lymphoma

Determine the correlation of the level of O6-methylguanine- methyltransferase (MGMT) (P140K) marking with toxicity and response. --- P140K ---

Primary Outcomes

Measure: Safety of infusion of gene-modified cells, measured by grade 3 or greater toxicities related to infusion of gene-modified cells using the Common Toxicity Criteria version 4.0(CTCv.4)

Time: Up to day 180

Measure: Safety of O6BG/BCNU in vivo selection, defined as less than 25% of patients developing grade 3 or greater non-hematopoietic toxicity or grade 4 CTCv.4 hematopoietic toxicity

Time: Up to day 180

Measure: Safety of structured treatment interruption defined as no decline in CD4 count by more than 25%, no HIV RNA more than 10,000 copies/mL; and no elevation of immune activation markers

Time: During the 12 weeks without HAART

Measure: Efficacy of gene transduction, defined as collection of more than 4.5 x 10^6 CD34+ cells/kg cells for genetic modification and evidence of gene-marked cells before HSC infusion

Time: Up to 3 months

Measure: Efficacy of infusion of gene-modified cells, defined as engraftment of at least1% gene-modified cells

Time: Up to 3 months

Measure: Efficacy of O6BG/BCNU in vivo selection, defined as selection of gene-modified cells to a level at least 10% of peripheral blood cells

Time: Up to 3 months

4 A Clinical Trial of Gene-Modified Stem Cells to Generate HIV-Resistant Cells in Conjunction With Standard Chemotherapy for Treatment of Lymphoma in Patients With HIV Infection

This pilot phase I trial studies the side effects and best dose of human immunodeficiency virus (HIV)-resistant gene modified stem cells in treating HIV-positive patients who are undergoing first-line treatment for Hodgkin or Non-Hodgkin Lymphoma. Stem cells are collected from the patient and HIV-resistance genes are placed into the stem cells. The stem cells are then re-infused into the patient. These genetically modified stem cells may help the body make cells that are resistant to HIV infection.

NCT02343666 Human Immunodeficiency Virus 1 Positive Stage I Adult Hodgkin Lymphoma Stage I Adult Non-Hodgkin Lymphoma Stage II Adult Hodgkin Lymphoma Stage II Adult Non-Hodgkin Lymphoma Stage III Adult Hodgkin Lymphoma Stage III Adult Non-Hodgkin Lymphoma Stage IV Adult Hodgkin Lymphoma Stage IV Adult Non-Hodgkin Lymphoma Biological: C46/CCR5/P140K Lentiviral Vector-transduced Autologous HSPCs Drug: Carmustine Biological: Filgrastim Other: Laboratory Biomarker Analysis Drug: O6-Benzylguanine Drug: Plerixafor
MeSH: HIV Infections Acquired Immunodeficiency Syndrome Lymphoma Lymphoma, Non-Hodgkin Hodgkin Disease
HPO: Hodgkin lymphoma Lymphoma Non-Hodgkin lymphoma

Inclusion Criteria: - HIV-1 seropositive - Stable, continuous antiretroviral treatment, defined as a multi-drug regimen (excluding zidovudine, also known as azidothymidine [AZT], Retrovir) prior to enrollment, as demonstrated by HIV plasma viral load < 50 copies/mL - Previously untreated non-Hodgkin lymphoma or Hodgkin lymphoma; all stages of disease are allowed; also eligible are patients who have started or completed one or more cycles of treatment as part of a planned first line regimen, or those who have received local radiation or surgery or corticosteroids for disease control - Planned treatment with standard first line therapy for non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) - Karnofsky performance score >= 70% - Subjects must agree to use effective means to prevent conception from enrollment through completion of the study - Female subjects: if of child bearing potential, must have negative serum or urine pregnancy test within 7 days of enrollment - Subjects must be on a prophylactic regimen for Pneumocystis jiroveci pneumonia, or agree to begin such treatment, if CD4+ cell counts are observed to be =< 200/ul in peripheral blood - Able to understand, and the willingness to give, informed consent for the study Exclusion Criteria: - Central nervous system (CNS) lymphoma: CNS involvement by lymphoma, including parenchymal brain or spinal cord lymphoma or known presence of leptomeningeal disease prior to registration - Patients with renal, hepatic, pulmonary, or cardiac disease that exclude delivery of standard chemotherapy - Active (uncontrolled) infection requiring systemic antibiotic therapy with antibacterial, antifungal, or antiviral agents (excluding HIV) - Hepatitis B surface antigen positive - Hepatitis C virus (HCV) antibody positive and detectable HCV quantitative ribonucleic acid (RNA), with clinical evidence of cirrhosis as determined by the principal investigator - Requiring active treatment for Toxoplasma gondii infection - Malignancy other than lymphoma, unless (1) in complete remission and more than 5 years from last treatment, or (2) cervical/anal squamous cell carcinoma in situ or (3) superficial basal cell and squamous cell cancers of the skin - History of HIV-associated encephalopathy; dementia of any kind; seizures in the past 12 months - Any perceived inability to directly provide informed consent (note: consent may not be obtained by means of a legal guardian) - Any concurrent or past medical condition that, in the opinion of the investigator, would exclude the subject from participation - Patients who have received a vaccine for HIV-1 or any prior gene modified cell product, at any time - A medical history of noncompliance with HAART or medical therapy - Pregnant women or nursing mothers - Use of zidovudine as part of the HAART regimen (a drug substitution for zidovudine at the time of study entry is allowed) - Known hypersensitivity to any of the products used in the trial - G-CSF (Neupogen, filgrastim), plerixafor (Mozobil), or any components of the chemotherapeutic agents or O6BG/BCNU in vivo selection regimens Inclusion Criteria: - HIV-1 seropositive - Stable, continuous antiretroviral treatment, defined as a multi-drug regimen (excluding zidovudine, also known as azidothymidine [AZT], Retrovir) prior to enrollment, as demonstrated by HIV plasma viral load < 50 copies/mL - Previously untreated non-Hodgkin lymphoma or Hodgkin lymphoma; all stages of disease are allowed; also eligible are patients who have started or completed one or more cycles of treatment as part of a planned first line regimen, or those who have received local radiation or surgery or corticosteroids for disease control - Planned treatment with standard first line therapy for non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) - Karnofsky performance score >= 70% - Subjects must agree to use effective means to prevent conception from enrollment through completion of the study - Female subjects: if of child bearing potential, must have negative serum or urine pregnancy test within 7 days of enrollment - Subjects must be on a prophylactic regimen for Pneumocystis jiroveci pneumonia, or agree to begin such treatment, if CD4+ cell counts are observed to be =< 200/ul in peripheral blood - Able to understand, and the willingness to give, informed consent for the study Exclusion Criteria: - Central nervous system (CNS) lymphoma: CNS involvement by lymphoma, including parenchymal brain or spinal cord lymphoma or known presence of leptomeningeal disease prior to registration - Patients with renal, hepatic, pulmonary, or cardiac disease that exclude delivery of standard chemotherapy - Active (uncontrolled) infection requiring systemic antibiotic therapy with antibacterial, antifungal, or antiviral agents (excluding HIV) - Hepatitis B surface antigen positive - Hepatitis C virus (HCV) antibody positive and detectable HCV quantitative ribonucleic acid (RNA), with clinical evidence of cirrhosis as determined by the principal investigator - Requiring active treatment for Toxoplasma gondii infection - Malignancy other than lymphoma, unless (1) in complete remission and more than 5 years from last treatment, or (2) cervical/anal squamous cell carcinoma in situ or (3) superficial basal cell and squamous cell cancers of the skin - History of HIV-associated encephalopathy; dementia of any kind; seizures in the past 12 months - Any perceived inability to directly provide informed consent (note: consent may not be obtained by means of a legal guardian) - Any concurrent or past medical condition that, in the opinion of the investigator, would exclude the subject from participation - Patients who have received a vaccine for HIV-1 or any prior gene modified cell product, at any time - A medical history of noncompliance with HAART or medical therapy - Pregnant women or nursing mothers - Use of zidovudine as part of the HAART regimen (a drug substitution for zidovudine at the time of study entry is allowed) - Known hypersensitivity to any of the products used in the trial - G-CSF (Neupogen, filgrastim), plerixafor (Mozobil), or any components of the chemotherapeutic agents or O6BG/BCNU in vivo selection regimens Human Immunodeficiency Virus 1 Positive Stage I Adult Hodgkin Lymphoma Stage I Adult Non-Hodgkin Lymphoma Stage II Adult Hodgkin Lymphoma Stage II Adult Non-Hodgkin Lymphoma Stage III Adult Hodgkin Lymphoma Stage III Adult Non-Hodgkin Lymphoma Stage IV Adult Hodgkin Lymphoma Stage IV Adult Non-Hodgkin Lymphoma HIV Infections Acquired Immunodeficiency Syndrome Lymphoma Lymphoma, Non-Hodgkin Hodgkin Disease PRIMARY OBJECTIVES: I. To determine the safety and feasibility of infusing C46/CCR5/P140K lentiviral vector-transduced autologous hematopoietic stem progenitor cells (HSPC) (gene modified, HIV-protected HSPC) after standard first line treatment of lymphoma in patients with HIV infection. --- P140K ---

Determine the correlation between the level of MGMT(P140K) marking with toxicity and response to O6BG/BCNU chemotherapy. --- P140K ---

STEM CELL INFUSION: Patients receive CD34+ gene-modified C46/CCR5/P140K lentiviral vector-transduced autologous HSPC intravenously (IV) within 2 to 8 days, but no later than 28 days, after completion of the last cycle of first line treatment for lymphoma. --- P140K ---

Primary Outcomes

Measure: Feasibility of collection: defined as collection of >= 4.0 x 10^6 CD34+ cells/kg for genetic modification

Time: Up to 28 days after completion of last course of first line treatment for lymphoma

Description: Engraftment of >= 1% gene modified cells.

Measure: Feasibility of infusion of gene modified cells: defined as engraftment of >= 1% gene modified cells

Time: Up to 28 days after infusion of gene-modified cells to 15 years post-transfusion

Measure: Feasibility of O6-benzylguanine/carmustine in vivo selection: defined as selection of gene modified cells to a level >= 10% of peripheral blood cells

Time: Up to 180 days after infusion of the gene modified hematopoietic stem progenitor cells

Measure: Feasibility of structured treatment interruption: defined as the ability to achieve >= 10% gene modified cell engraftment level and maintain CD4 counts and plasma viremia at levels required for structured treatment interruption eligibility

Time: Up to 18 months following infusion of CD34+ gene modified hematopoietic stem progenitor cells

Description: Any development of confirmed replication competent lentivirus in any patient receiving gene modified cells during the study will be recorded.

Measure: Presence of confirmed replication competent lentivirus

Time: Up to 15 years

Description: Confirmed insertional mutagenesis in any patient who received gene modified cells during the study

Measure: Presence of insertional mutagenesis

Time: Up to 15 years

Measure: Safety of infusion of gene modified cells: defined as Common Terminology Criteria for Adverse Events version 4 toxicity >= grade 3 related to the infusion of gene modified cells

Time: Up to 30 days after infusion of CD34+ modified hematopoietic stem progenitor cells

Measure: Safety of O6-benzylguanine/carmustine in vivo selection, defined as < 25% of patients developing Common Terminology Criteria for Adverse Events version 4 toxicity >= grade 3 associated with O6-benzylguanine/carmustine administration

Time: Up to 15 years


HPO Nodes


Non-Hodgkin lymphoma
Genes 32
ATM FAS CASP10 CTLA4 FAS BCL10 CD28 BIRC3 FOXP1 TNFRSF1B MYC CCND1 ASXL1 ATM MALT1 CTLA4 CD28 SRSF2 KIT POLE IGH ADA TET2 FASLG PIK3R1 NTHL1 RASGRP1 TNFRSF1B PRKCD NBN RHOH IGH
Hodgkin lymphoma
Genes 15
ATM TCF4 POLE FAS DKC1 CASP10 TCF4 FAS FASLG COL14A1 RNF43 AAGAB RASGRP1 PRKCD KLHDC8B
Glioblastoma multiforme
Genes 23
FAN1 APC BMPR1A KRAS BRCA2 RPS20 MLH1 MSH2 MSH6 EPCAM PMS2 MLH1 MLH3 PMS2 PMS1 MSH6 TP53 MSH2 TGFBR2 PIK3CA SEMA4A ERBB2 IDH1
Lymphoma
Genes 133
ATM KRAS CD19 IGH DDX41 BCL10 BIRC3 FOXP1 MS4A1 TP63 RAG1 LIG4 NFKB2 MSH6 TERC RECQL4 NTHL1 WIPF1 CTC1 LYST NOP10 RASGRP1 TNFRSF1B XRCC4 PRKCD NHP2 MAGT1 TNFRSF13B IGH RMRP RUNX1 CTLA4 DCLRE1C FAS ICOS RNF43 NSUN2 XIAP IL7R CASP10 BCL6 CDKN2A ATM IL2RG RTEL1 PARN NBN KIT TNFRSF13C TCF4 ICOS TNFSF12 CHEK2 USB1 CD19 CR2 NRAS MSH2 WAS BCL10 CASP10 MYD88 COL14A1 PRKCD TNFRSF13B MYC MDM2 SH2D1A CCND1 BCL10 CFTR CD27 PGM3 TCF4 CHD7 IGH LIG4 BLM BCL2 TET2 HLA-DRB1 PRSS1 NPM1 KIF11 ITK WRAP53 RAD54B TINF2 FAS DKC1 APC CD81 LIG4 BLM CD28 DKC1 AAGAB RAG2 TNFRSF1B MLH1 TNFRSF13C DNASE1L3 NFKB1 PMS2 ASXL1 IL2RG PRF1 PTEN MALT1 RAD54L CTLA4 CD28 PNP SRSF2 TNFSF12 STAT3 POLE ADA CR2 ADA FASLG PIK3R1 TP53 CTRC ZAP70 MYD88 RB1 RMRP SPINK1 TERT KLHDC8B NBN RHOH
Chronic lymphatic leukemia
Genes 8
ADAR TREX1 IFIH1 PIK3R1 RNASEH2A SAMHD1 RNASEH2B RNASEH2C
Leukemia
Genes 190
ATM KRAS KIT RPS15A NF1 MPL RPL35A RPL11 RPL18 DDX41 SBDS LPP ETV6 BUB1B F13A1 DNMT3A JAK2 NUP214 FANCD2 MSH6 FANCA PIGL NRAS TCIRG1 BUB1 TET2 FLT3 TAL1 ATRX TREX1 PDGFRA SRP54 RPS29 PTPN11 CALR FANCE WIPF1 SF3B1 GATA2 GLI1 STS SH3GL1 XRCC4 MPL SH2B3 EFL1 PIGA TREM2 CBL MPL RUNX1 MPL PIGL THPO FANCG NSD1 BRD4 NSUN2 SH2B3 RARA GATA2 NPM1 CBL CHIC2 ERBB3 GFI1 TERT KIT BCR ARHGAP26 DYNC2LI1 EVC SCN10A GATA1 ELANE RNASEH2B RPS14 SH2B3 JAK2 RPL15 SBDS NRAS RPL26 RPL27 ADA2 RPS7 TYROBP F13B MSH2 BCR WAS TERC TP53 TRIP13 MYD88 NUTM1 RPS24 GNB1 TP53 DNMT3A TERT NUMA1 NUP214 RPL5 SAMD9L TET2 CFTR POT1 FANCC RPS10 EP300 EVC2 BUB1B CEBPA BRCA2 DNAJC21 CALR SCN9A LIG4 ADAR BLM TET2 JAK2 SMPD1 RNASEH2C SCN11A GATA2 BUB3 PRSS1 KIF11 BCR RPL35 TAL2 SRP54 IFIH1 ABL1 PDGFRB KRAS RNASEH2A TET2 MLLT10 SRP54 DNAJC21 DKC1 RUNX1 APC LIG4 CBFB BLM THPO CALR NBN JAK2 MLH1 RPS19 ELANE SAMD9L RPL31 PMS2 ASXL1 TSR2 MLF1 PIK3CA DNAJC21 RUNX1 GFI1 SRSF2 SETBP1 HAX1 RPS26 RPS17 FLT3 RPS27 PIK3R1 KRAS CEP57 PICALM CREBBP GATA2 CTRC MYD88 TET2 RPS28 ABL1 RB1 SPINK1 GATA1 NBN JAK2 SAMHD1
Anaplastic large-cell lymphoma
T-cell lymphoma
Genes 14
POLE FAS CASP10 CTLA4 FAS FASLG CD28 TNFRSF1B RASGRP1 TNFRSF1B PRKCD CTLA4 CD28 NBN
Monoclonal immunoglobulin M proteinemia
Genes 2
MYD88 MYD88
B-cell lymphoma
Genes 17
IGH FAS CASP10 ADA FAS FASLG BCL10 PIK3R1 BIRC3 FOXP1 RASGRP1 CCND1 ATM PRKCD MALT1 NBN IGH
Cutaneous T-cell lymphoma
Genes 6
CTLA4 TNFRSF1B CD28 CTLA4 CD28 TNFRSF1B
Glioma
Genes 50
TSC2 GLI3 BRCA2 TSC1 LRP5 MLH1 PMS2 APC IDH1 MSH6 POT1 TSC2 CDKN2A NF2 MSH3 MSH6 APC NF1 EPCAM TSC1 TGFBR2 SEMA4A IDH1 IDH2 FAN1 APC MSH3 BMPR1A KRAS MLH1 MSH2 C11ORF95 PMS2 MLH3 PIK3CA NBN RELA SETBP1 IFNG RPS20 NF1 PMS1 CHEK2 APC TP53 MSH2 NBN ERBB2 APC NF2
Burkitt lymphoma
Genes 8
RASGRP1 FAS CASP10 FAS FASLG PRKCD RHOH MYC