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

NCT02627677 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: AP24534-15-3032015-001318-92
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

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).

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

Outcome Measures

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.

  Up to 12 months

Secondary Outcomes (12)

• Percentage of Participants With Major Cytogenetic Response (MCyR)

  Up to 12 months

• Percentage of Participants With Complete Cytogenetic Response (CCyR)

  Up to 12 months

• Percentage of Participants With Molecular Response (MR)

  From Month 3 to every 3 months up to 48 months

• Percentage of Participants With MR1

  Month 3

• 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)

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

Study Arms (3)

Cohort A: Ponatinib 30 mg

EXPERIMENTAL

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

Cohort B: Ponatinib 15 mg

EXPERIMENTAL

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

Cohort C: Nilotinib 400 mg

ACTIVE COMPARATOR

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

Drug: Nilotinib 400 mg BID

Interventions

Ponatinib 30 mg QD DRUG

Ponatinib 30 mg, taken orally once daily.

Also known as: Iclusig, AP24534

Cohort A: Ponatinib 30 mg

Ponatinib 15 mg QD DRUG

Ponatinib 15 mg, taken orally once daily.

Also known as: Iclusig, AP24534

Cohort B: Ponatinib 15 mg

Nilotinib 400 mg BID DRUG

Nilotinib 400 mg, taken orally twice daily.

Also known as: Tasigna, AMN107

Cohort C: Nilotinib 400 mg

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Have CP-CML and are resistant to first-line imatinib treatment.
• Be male or female ≥18 years old.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Have adequate renal function as defined by the following criterion:
• Serum creatinine ≤1.5 × upper limit of normal (ULN) for institution.
• 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.
• Have normal pancreatic status as defined by the following criterion:
• Serum lipase and amylase ≤1.5 × ULN.

You may not qualify if:

• 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.
• Have previously been treated with any anti-CML therapy other than hydroxyurea, including interferon, cytarabine, immunotherapy, or any cytotoxic chemotherapy, radiotherapy, or investigational therapy.
• Underwent autologous or allogeneic stem cell transplant.
• Are in CCyR or MMR.
• 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.

Sponsors & Collaborators

• Ariad Pharmaceuticals: lead

Study Sites (1)

Cliniques Universitaire Saint-Luc (Site 058)

Brussels, 1200, Belgium

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Chronic-Phase; Leukemia; Leukemia, Myeloid; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Neoplasms by Histologic Type; Neoplasms; Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases

Interventions

ponatinib; nilotinib; BID protein, human

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Limitations and Caveats

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

Results Point of Contact

• Title: Study Director
• Organization: Takeda

TrialDisclosures@takeda.com

+1-877-825-3327

Study Officials

• Study Director

  Takeda

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2015
• First Posted: December 11, 2015
• Study Start: December 31, 2015
• Primary Completion: October 29, 2020
• Study Completion: January 20, 2021
• Last Updated: November 26, 2021
• Results First Posted: November 26, 2021

Record last verified: 2021-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Access Criteria: IPD from eligible studies will be shared with qualified researchers according to the criteria and process described on https://vivli.org/ourmember/takeda/. For approved requests, the researchers will be provided access to anonymized data (to respect patient privacy in line with applicable laws and regulations) and with information necessary to address the research objectives under the terms of a data sharing agreement.

Locations

BE (1)