Neoplasms

Blood and Lymph Conditions

All Conditions

Symptoms and General Pathology

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Leukemia, Myeloid, Chronic-Phase

Myeloproliferative Disorders

Bone Marrow Diseases

Hematologic Diseases

Neoplasms by Histologic Type

Chronic Disease

Disease Attributes

Myeloid Leukemia

Chronic Graft Versus Host Disease

Chronic Myeloid Leukemia

Chronic Myeloproliferative Disorders

All Drugs and Chemicals

Antineoplastic Agents

Amino Acids

Nilotinib

Ponatinib

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to 42 months.

Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to 45 months.

Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.

Ponatinib 30 mg, taken orally once daily.

Ponatinib 30 mg QD

Ponatinib 15 mg, taken orally once daily.

Ponatinib 15 mg QD

Nilotinib 400 mg, taken orally twice daily.

Nilotinib 400 mg BID

Study Director

The purpose of this study is to compare the efficacy and safety of 2 starting doses of ponatinib compared to nilotinib in participants with imatinib-resistant chronic myeloid leukemia (CML) in chronic phase (CP).

This is a multi-center, randomized study to demonstrate the efficacy and safety of 2 starting doses of ponatinib as a treatment for CP-CML compared to nilotinib. Eligible participants must have chronic phase chronic myeloid leukemia (CP-CML), be resistant to first-line imatinib treatment and have received no other tyrosine kinase inhibitors (TKIs).

A Study Comparing Ponatinib and Nilotinib in Participants With Chronic Myeloid Leukemia

A Randomized, Open-label Study of Ponatinib Versus Nilotinib in Patients With Chronic Myeloid Leukemia in Chronic Phase Following Resistance to Imatinib

Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.

MMR is defined as the percentage of participants achieving a ratio of ≤0.1% Breakpoint Cluster Region-Abelson (BCR ABL) to ABL transcripts on the international scale (≤0.1% BCR-ABL/ABL\[IS\]) at any time within 12 months after randomization.

MCyR was the percentage of participants achieving Complete cytogenetic response (CCyR: defined as 0% Philadelphia chromosome-positive \[Ph+\] metaphases by cytogenetic analysis of bone marrow) or Partial Cytogenetic Response (PCyR: defined as \>0% to 35% Ph+ metaphases by cytogenetic analysis of bone marrow) at any time within 12 months after randomization.

CCyR rate was defined as the percentage of participants achieving CCyR up to 12 months after randomization. CCyR is defined as 0% Philadelphia chromosome-positive \[Ph+\] metaphases by cytogenetic analysis of bone marrow.

Molecular response rate is defined as percentage of participants achieving MR2: Molecular response with 2-log reduction (defined as ≤1% BCR-ABL\[IS\]), MMR: Major molecular responder, MR4 (defined as ≤0.01% BCR-ABL\[IS\]), and MR4.5 (defined as ≤0.0032% BCR-ABL\[IS\]) after randomization.

MR1 was defined as the percentage of participants achieving a ratio of ≤10% BCR ABL to ABL transcripts on the international scale at 3 months.

TE-AOE: arterial occlusive event with an initial onset date on or after first dose date and no later than 30 days after last dose date of study treatment or events starting after initial consent that worsen in severity on or after first dose date. TE-VTE: vascular occlusive event with an initial onset date on or after first dose date and no later than 30 days after last dose date of study treatment or events starting after initial consent that worsen in severity on or after first dose date. AE: any untoward medical occurrence in participant administered pharmaceutical product; untoward medical occurrence does not necessarily have causal relationship with this treatment. SAE: any untoward medical occurrence that at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of an existing hospitalization, results in persistent or significant disability or incapacity, is congenital anomaly/birth defect/is medically important event.

Time to MMR defined as the interval between the randomization date and the first date at which the criteria for response was met. MMR was defined as \<=0.1% BCR-ABL.

Duration of response defined as the interval between the first assessment at which the criteria for response was met until the earliest date at which loss of response occurs, or the criteria for progression was met.

Progression-free survival (PFS) defined as the interval between the first dose date of study treatment and the first date at which the criteria for progression was met (progression to AP- or BP CML), or death due to any cause, censored at the last response assessment.

Overall survival (OS) defined as the interval between the first dose date of study treatment and date of death due to any cause, censored at the last contact date to be alive.

CHR rate is defined as the percentage of participants achieving CHR at any time after initiation of study treatment. CHR is defined as achieving all of the following measurements: White blood cells (WBC) ≤ institutional upper limit of normal (ULN); Platelets \<450 x 10\^9/L; No blasts or promyelocytes in peripheral blood; \<5% myelocytes plus metamyelocytes in peripheral blood; Basophils in peripheral blood \<5%; No extramedullary involvement (including no hepatomegaly or splenomegaly).

An AE is defined as any untoward medical occurrence in a clinical investigation participant administered a drug; it does not necessarily have to have a causal relationship with this treatment. A TEAE is defined as an adverse event with an onset that occurs after receiving study drug.

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\*10\^9 platelets/L in peripheral blood unrelated to therapy or cytogenetic, genetic evidence of clonal evolution, and no extramedullary disease. Progression to BP-CML is defined as: \>=30% blasts in peripheral blood or bone marrow or extramedullary disease other than hepatosplenomegaly.

Ariad Pharmaceuticals

At each visit the investigator had to document any occurrence of adverse events and abnormal laboratory findings. Any event spontaneously reported by the participant or observed by the investigator was recorded, irrespective of the relation to study treatment. Safety Population includes all participants who have received at least 1 dose of study drug.

Ponatinib 30 mg, tablets, orally, once daily (QD) until achievement of major molecular response (MMR) up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 42 months.

Cohort A: Ponatinib 30 mg

Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45 months.

Cohort B: Ponatinib 15 mg

Cohort C: Nilotinib 400 mg

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Austria

Canada

Czech Republic

France

Hungary

Italy

Korea, North

Russia

Region of Enrollment

Number analyzed is the number of participants with data available for Height at Baseline.

Height

Weight

BMI is calculated as weight (kg) divided by square of height (m\^2).

Number analyzed is the number of participants with data available for BMI at Baseline.

Body Mass Index (BMI)

Safety Population included all participants who have received at least 1 dose of study drug.

This study was terminated due to operational feasibility and not due to any safety concerns.

Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis.

Percentage of Participants With Major Molecular Response (MMR)

Percentage of Participants With Major Cytogenetic Response (MCyR)

Percentage of Participants With Complete Cytogenetic Response (CCyR)

MR2 - Month 3

MR2 - Month 6

MR2 - Month 9

MR2 - Month 12

MR2 - Month 15

MR2 - Month 18

MR2 - Month 21

MR2 - Month 24

MR2 - Month 27

MR2 - Month 30

MR2 - Month 33

MR2 - Month 36

MR2 - Month 39

MR2 - Month 42

MR2 - Month 45

MR2 - Month 48

MR3/MMR - Month 3

MR3/MMR - Month 6

MR3/MMR - Month 9

MR3/MMR - Month 12

MR3/MMR - Month 15

MR3/MMR - Month 18

MR3/MMR - Month 21

MR3/MMR - Month 24

MR3/MMR - Month 27

MR3/MMR - Month 30

MR3/MMR - Month 33

MR3/MMR - Month 36

MR3/MMR - Month 39

MR3/MMR - Month 42

MR3/MMR - Month 45

MR3/MMR - Month 48

MR4 - Month 3

MR4 - Month 6

MR4 - Month 9

MR4 - Month 12

MR4 - Month 15

MR4 - Month 18

MR4 - Month 21

MR4 - Month 24

MR4 - Month 27

MR4 - Month 30

MR4 - Month 33

MR4 - Month 36

MR4 - Month 39

MR4 - Month 42

MR4 - Month 45

MR4 - Month 48

MR4.5 - Month 3

MR4.5 - Month 6

MR4.5 - Month 9

MR4.5 - Month 12

MR4.5 - Month 15

MR4.5 - Month 18

MR4.5 - Month 21

MR4.5 - Month 24

MR4.5 - Month 27

MR4.5 - Month 30

MR4.5 - Month 33

MR4.5 - Month 36

MR4.5 - Month 39

MR4.5 - Month 42

MR4.5 - Month 45

MR4.5 - Month 48

Safety Population included all participants who have received at least 1 dose of study drug, with data available for analysis. Number analyzed are participants with data available for analyses at given timepoint.

Percentage of Participants With Molecular Response (MR)

Safety Population includes all participants who have received at least 1 dose of study drug, with data available for analysis.

Percentage of Participants With MR1

TE-AOE

TE-VOEs

SAEs

Safety Population includes all participants who have received at least 1 dose of study drug.

Percentage of Participants With Treatment Emergent Arterial Occlusive Events (TE-AOEs), Treatment Emergent Venous Thromboembolic Events (TE-VTE), Adverse Events (AEs), and Serious AEs (SAEs)

Safety Population includes all participants who have received at least 1 dose of study drug. Only responders were analyzed for this outcome measure.

Time to Response

Duration of Response

Progression-free Survival (PFS)

Ponatinib 15 mg, tablets, orally, QD until achievement of MMR up to 12 months. Once MMR was achieved, participants received reduced dose of ponatinib 15 mg orally once daily up to approximately 45months.

Overall Survival

Percentage of Participants Who Achieved/Maintained Complete Hematologic Response (CHR)

TEAEs Leading to Treatment Discontinuation

TEAEs Leading to Dose Reduction

TEAEs Leading to Dose Interruption

Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption

As the study was terminated, data was not collected and analyzed for this outcome measure.

Spots Global Cancer Trial Database for nilotinib 400 mg bid