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

Browse trials for

• Leukemia 5,441
• Leukemia, Myeloid 2,443
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive 964
• Leukemia, Myeloid, Chronic-Phase 183

Keywords

• CML
• CP-CML
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myelogenous, Chronic, BCR-ABL Positive
• Neoplasms by Histologic Type
• Neoplasms
• Myeloproliferative Disorders
• Bone Marrow Diseases
• Hematologic Diseases

Leukemia

5,441 studies on the registry are indexed under Leukemia; 636 are open to participants now.

This study's enrollment of 44 is above the median of 38 across 4,247 interventional studies indexed under Leukemia.

Lead sponsor

Ariad Pharmaceuticals is the lead sponsor of 13 studies on the registry; none are open to participants now.

Of its 5 completed or terminated interventional studies of FDA-regulated products, 5 (100%) have results posted.

Study arms

• Experimental
  Cohort A: Ponatinib 30 mg

  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.

  Drug: Ponatinib 30 mg QD

• Experimental
  Cohort B: Ponatinib 15 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 45 months.

  Drug: Ponatinib 15 mg QD

• Active comparator
  Cohort C: Nilotinib 400 mg

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

  Drug: Nilotinib 400 mg BID

Interventions

• DrugPonatinib 30 mg QD

  Ponatinib 30 mg, taken orally once daily.

  Also known as: Iclusig, AP24534

• DrugPonatinib 15 mg QD

  Ponatinib 15 mg, taken orally once daily.

  Also known as: Iclusig, AP24534

• DrugNilotinib 400 mg BID

  Nilotinib 400 mg, taken orally twice daily.

  Also known as: Tasigna, AMN107

Primary outcomes

1. Percentage of Participants With Major Molecular Response (MMR)

   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.

   Time frame: Up to 12 months

Secondary outcomes

1. Percentage of Participants With Major Cytogenetic Response (MCyR)

   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.

   Time frame: Up to 12 months

2. Percentage of Participants With Complete Cytogenetic Response (CCyR)

   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.

   Time frame: Up to 12 months

3. Percentage of Participants With Molecular Response (MR)

   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.

   Time frame: From Month 3 to every 3 months up to 48 months

4. Percentage of Participants With MR1

   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.

   Time frame: Month 3

5. 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)

   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 frame: From first dose up to 30 days post last dose (Up to approximately 46 months)

6. Time to Response

   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.

   Time frame: Up to approximately 60 months

7. Duration of Response

   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.

   Time frame: Up to approximately 60 months

8. Progression-free Survival (PFS)

   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.

   Time frame: Up to end of study (approximately 60 months)

9. Overall Survival

   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.

   Time frame: Up to end of study (approximately 60 months)

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

    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).

    Time frame: 3 months after the first dose of study treatment

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

    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.

    Time frame: From first dose up to end of treatment (Up to approximately 45 months)

12. Percentage of Participants With Progression to Accelerated Phase (AP) or Blast Phase (BP)-CML

    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.

    Time frame: Up to end of study (Up to approximately 60 months)

Baseline characteristics

Study documents

• Study protocol · Mar 10, 2017
• Statistical analysis plan · Jul 31, 2016

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — 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.

Supporting information: Study protocol, Sap, Icf, Csr