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

NCT ID: NCT02627677

Last Updated: 2021-11-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 44 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2021-01-20

Brief Summary

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).

Detailed Description

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).

Conditions

Chronic Phase Chronic Myeloid Leukemia

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Ponatinib 30 mg QD

Intervention Type: DRUG

Ponatinib 30 mg, taken orally once daily.

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.

Group Type: EXPERIMENTAL

Ponatinib 15 mg QD

Intervention Type: DRUG

Ponatinib 15 mg, taken orally once daily.

Cohort C: Nilotinib 400 mg

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

Group Type: ACTIVE_COMPARATOR

Nilotinib 400 mg BID

Intervention Type: DRUG

Nilotinib 400 mg, taken orally twice daily.

Interventions

Ponatinib 30 mg QD

Ponatinib 30 mg, taken orally once daily.

Intervention Type: DRUG

Ponatinib 15 mg QD

Ponatinib 15 mg, taken orally once daily.

Intervention Type: DRUG

Nilotinib 400 mg BID

Nilotinib 400 mg, taken orally twice daily.

Intervention Type: DRUG

Other Intervention Names

Iclusig; AP24534; Iclusig; AP24534; Tasigna; AMN107

Eligibility Criteria

Inclusion Criteria

1. Have CP-CML and are resistant to first-line imatinib treatment.

2. Be male or female ≥18 years old.

3. Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

4. Have adequate renal function as defined by the following criterion:

• Serum creatinine ≤1.5 × upper limit of normal (ULN) for institution.

5. Have adequate hepatic function as defined by all of the following criteria:

• Total serum bilirubin ≤1.5 × ULN, unless due to Gilbert's syndrome
• Alanine aminotransferase (ALT) ≤2.5 × ULN or ≤5 × ULN if leukemic infiltration of the liver is present
• Aspartate aminotransferase (AST) ≤2.5 × ULN or ≤5 × ULN if leukemic infiltration of the liver is present.

6. Have normal pancreatic status as defined by the following criterion:

• Serum lipase and amylase ≤1.5 × ULN.

Exclusion Criteria

1. Have previously been treated with any approved or investigational TKIs other than imatinib or treated with imatinib within 14 days prior to receiving study drug.

2. Have previously been treated with any anti-CML therapy other than hydroxyurea, including interferon, cytarabine, immunotherapy, or any cytotoxic chemotherapy, radiotherapy, or investigational therapy.

3. Underwent autologous or allogeneic stem cell transplant.

4. Are in CCyR or MMR.

5. Have clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:

• Any history of myocardial infarction (MI), unstable angina, cerebrovascular accident, or transient ischemic attack (TIA)
• Any history of peripheral vascular infarction, including visceral infarction
• Any history of a revascularization procedure, including vascular surgery or the placement of a stent
• History of venous thromboembolism, including deep venous thrombosis, superficial venous thrombosis, or pulmonary embolism, within 6 months prior to enrollment
• Congestive heart failure (New York Heart Association [NYHA] class III or IV) within 6 months prior to enrollment or left ventricular ejection fraction (LVEF) less than 45% or less than the institutional lower limit of normal (whichever is higher) within 6 months prior to enrollment.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ariad Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Study Director

Role: STUDY_DIRECTOR

Takeda

Locations

Cliniques Universitaire Saint-Luc (Site 058)

Brussels, , Belgium

Countries

Belgium

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-001318-92

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AP24534-15-303

Identifier Type: -

Identifier Source: org_study_id