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Report for Clinical Trial NCT02467270

Developed by Shray Alag, 2020.
SNP Clinical Trial Gene

A Randomized, Open-label, Phase 2 Trial of Ponatinib in Patients With Resistant Chronic Phase Chronic Myeloid Leukemia to Characterize the Efficacy and Safety of a Range of Doses

The purpose of this study is to characterize the efficacy of ponatinib administered in 3 starting doses (45 milligram [mg], 30 mg, and 15 mg daily) in participants with CP-CML who are resistant to prior tyrosine-kinase inhibitor (TKI) therapy or have T315I mutation, as measured by less than or equal to (<=) 1 percent (%) Breakpoint Cluster Region-Abelson Transcript Level using International Scale (BCR-ABL1IS) at 12 months.

NCT02467270 Myeloid Leukemia, Chronic, Chronic Phase
MeSH:Leukemia Leukemia, Myeloid Leukemia, Myelogenous, Chronic, BCR-ABL Positive Leukemia, Myeloid, Chronic-Phase
HPO:Chronic myelogenous leukemia Leukemia Myeloid leukemia

3 Interventions

Name: Ponatinib 45 mg

Description: 45 mg tablet, taken orally once daily.
Type: Drug
Group Labels: 1

Cohort A

Name: Ponatinib 30 mg

Description: 30 mg tablet, taken orally once daily.
Type: Drug
Group Labels: 1

Cohort B

Name: Ponatinib 15 mg

Description: 15 mg tablet, taken orally once daily.
Type: Drug
Group Labels: 1

Cohort C


Primary Outcomes

Measure: Percentage of Participants with <=1% BCR-ABL1IS at Month 12

Time: Month 12

Secondary Outcomes

Description: MMR is defined as percentage of participants with major molecular response.

Measure: Percentage of Participants With Major Molecular Response (MMR) at Months 12 and 24

Time: Months 12 and 24

Description: MCyR is defined as percentage of participants with complete cytogenetic response (CCyR) or partial cytogenetic response (PCyR). Cytogenetic response is the percentage of Philadelphia chromosome positive (Ph+) metaphases in bone marrow (BM). Response is further defined as MCyR: CCyR or PCyR, where CCyR: 0% Ph + metaphases; PCyR: greater than (>) 0 to 35% Ph + metaphases.

Measure: Major Cytogenetic Response (MCyR) Rates by Month 12

Time: Up to Month 12

Description: Duration of MMR is defined as the interval between the first assessment at which the criteria for <=1% MMR are met until the earliest date at which loss of <=1% MMR occurs, or the criteria for progression are met.

Measure: Duration of MMR

Time: Baseline up to Month 24

Description: Percentage of participants with adjusted incidence rates who developed AOEs and VTEs will be categorized according to arterial occlusive events (Cardiac occlusive/thrombotic events, cerebral occlusive/thrombotic events and peripheral occlusive/thrombotic events) and venous thrombotic events.

Measure: Percentage of Participants with Adjusted Incidence Rates for Arterial Occlusive Events (AOEs) and Venous Thrombotic Events (VTEs), Adverse Events (AEs), and Serious AEs (SAEs)

Time: Baseline up to Month 24

Description: Cytogenetic response is the percentage of Ph+ metaphases in bone marrow (peripheral blood may not be used), with a review of a minimum of 20 metaphases. CCyR is defined as 0% Ph+ metaphases.

Measure: Percentage of Participants With CCyR at Month 12

Time: Month 12

Description: MR4 is defined as <=0.01% BCR-ABL1IS. MR 4.5 is defined as <=0.0032% BCR-ALB1IS.

Measure: Percentage of Participants With Major Molecular Response (MMR), Molecular Response 4 (MR4) and Molecular Response (MR4.5)

Time: Baseline up to Month 24

Description: MR1 is defined as percentage of participants achieving a ratio of <=10% Breakpoint Cluster Region-abelson (BCR-ABL1) transcripts on the international scale.

Measure: Percentage of Participants With Molecular Response 1 (MR1) at Month 3

Time: Month 3

Description: CHR is defined as achieving all of the following measurements: white blood cells (WBC) <= institutional upper limit of normal (ULN), platelets less than (<) 450,000 per cubic millimeter (/mm^3), no blasts or promyelocytes in peripheral blood, <5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood <5%, and no extramedullary involvement (including no hepatomegaly or splenomegaly).

Measure: Percentage of Participants With Complete hematologic Response (CHR) at Month 3

Time: Month 3

Measure: Percentage of Participants with AEs Leading to Discontinuation and Dose Reduction

Time: Baseline up to Month 24

Measure: Percentage of Participants with Dose Interruptions

Time: Baseline up to Month 24

Description: Duration of <=1% BCR-ABL1IS is defined as the interval between the first assessment at which the criteria for <=1% BCR-ABL1IS are met until the earliest date at which loss of <=1% BCR-ABL1IS occurs, or the criteria for progression (progression to accelerated phase [AP] or blast phase [BP] of CML) are met. Loss of <=1% BCR-ABL1IS is an increase to >1% of BCR-ABL1IS. Progression to AP is defined as: greater than or equal to (>=) 15% and <30% blasts in peripheral blood or bone marrow or >=20% basophils in peripheral blood or bone marrow or >=30% blasts + promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*109 platelets per liter (/L) in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP is defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.

Measure: Duration of Response (DOR) of <=1% BCR-ABL1 IS

Time: From the first assessment at which the criteria for <= 1% BCR-ABL1IS are met until the earliest date at which loss of <= 1% BCR-ABL1IS occurs, or the criteria for progression are met (up to 6.3 years)

Description: Duration of MMR is defined as the interval between the first assessment at which the criteria for MMR are met until the earliest date at which loss of MMR occurs, or the criteria for progression (progression to AP or BP of CML) are met. Participants remaining in MMR will be censored at the last date at which the criteria for MMR are met. Loss of MMR is an increase to >1% of BCR-ABL1IS. Progression to AP is defined as: >= 15% and <30% blasts in peripheral blood or bone marrow or >=20% basophils in peripheral blood or bone marrow or >=30% blasts + promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*109 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP is defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.

Measure: DOR for MMR

Time: From the first assessment at which the criteria for MMR are met until the earliest date at which loss of MMR occurs, or the criteria for progression are met (up to 6.3 years)

Description: Responders are defined as those participants who meet all of the following: are randomized and treated, respond at 12 months after the initiation of study treatment, and undergo baseline polymerase chain reaction (PCR) assessment.

Measure: DOR in Responders

Time: Baseline up to 6.3 years

Measure: Time to Response

Time: Baseline up to 6.3 years

Description: Progression to AP is defined as: >=15% and <30% blasts in peripheral blood or bone marrow or >=20% basophils in peripheral blood or bone marrow or >=30% blasts + promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*109 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP is defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.

Measure: Percentage of Participants With Progression to AP or BP CML

Time: From first dose date of study treatment until death due to any cause, censored at the last response assessment (up to 6.3 years)

Description: PFS is defined as the interval between the first dose date of study treatment and the first date at which the criteria for progression are met (progression to the AP or BP of CML), or death due to any cause, censored at the last response assessment. Progression to AP is defined as: >=15% and <30% blasts in peripheral blood or bone marrow or >=20% basophils in peripheral blood or bone marrow or >=30% blasts + promyelocytes in peripheral blood or bone marrow (but <30% blasts) or <100*109 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP is defined as: >=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.

Measure: Progression-free Survival (PFS)

Time: From first dose date of study treatment until first date at which criteria for progression are met, or death due to any cause, censored at the last response assessment (up to 6.3 years)

Description: OS is defined as the interval between the first does of study treatment and death due to any cause, censored at the last contact date when the participant was alive.

Measure: Overall Survival (OS)

Time: From first dose date of study treatment until death due to any cause, censored at the last contact date when the participant was alive (up to 6.3 years)

Purpose: Treatment

Allocation: Randomized

Parallel Assignment


There is one SNP

SNPs


1 T315I

Ponatinib in Participants With Resistant Chronic Phase Chronic Myeloid Leukemia (CP-CML) to Characterize the Efficacy and Safety of a Range of Doses The purpose of this study is to characterize the efficacy of ponatinib administered in 3 starting doses (45 milligram [mg], 30 mg, and 15 mg daily) in participants with CP-CML who are resistant to prior tyrosine-kinase inhibitor (TKI) therapy or have T315I mutation, as measured by less than or equal to (<=) 1 percent (%) Breakpoint Cluster Region-Abelson Transcript Level using International Scale (BCR-ABL1IS) at 12 months. --- T315I ---

OS is defined as the interval between the first does of study treatment and death due to any cause, censored at the last contact date when the participant was alive.. Inclusion Criteria: 1. Have CP-CML and have received at least two prior TKI therapies and have demonstrated resistance to treatment OR have documented history of presence of T315I mutation after receiving any number of prior TKI. --- T315I ---

Inclusion Criteria: 1. Have CP-CML and have received at least two prior TKI therapies and have demonstrated resistance to treatment OR have documented history of presence of T315I mutation after receiving any number of prior TKI. --- T315I ---



HPO Nodes


HPO: