Clinical trial NCT02627677: A Study Comparing Ponatinib and Nilotinib in Participants With Chronic Myeloid Leukemia
Official title: A Randomized, Open-label Study of Ponatinib Versus Nilotinib in Patients With Chronic Myeloid Leukemia in Chronic Phase Following Resistance to Imatinib
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
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
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2015-12-11
Enrollment: 44
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Percentage of Participants With Major Molecular Response (MMR)
timeFrame: Up to 12 months
Secondary outcomes:
measure: Percentage of Participants With Major Cytogenetic Response (MCyR)
timeFrame: Up to 12 months
measure: Percentage of Participants With Complete Cytogenetic Response (CCyR)
timeFrame: Up to 12 months
measure: Percentage of Participants With Molecular Response (MR)
timeFrame: From Month 3 to every 3 months up to 48 months
measure: Percentage of Participants With MR1
timeFrame: Month 3
measure: 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)
timeFrame: From first dose up to 30 days post last dose (Up to approximately 46 months)
measure: Time to Response
timeFrame: Up to approximately 60 months
measure: Duration of Response
timeFrame: Up to approximately 60 months
measure: Progression-free Survival (PFS)
timeFrame: Up to end of study (approximately 60 months)
measure: Overall Survival
timeFrame: Up to end of study (approximately 60 months)
measure: Percentage of Participants Who Achieved/Maintained Complete Hematologic Response (CHR)
timeFrame: 3 months after the first dose of study treatment
measure: Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption
timeFrame: From first dose up to end of treatment (Up to approximately 45 months)
measure: Percentage of Participants With Progression to Accelerated Phase (AP) or Blast Phase (BP)-CML
timeFrame: Up to end of study (Up to approximately 60 months)
Other outcomes:
Locations:
city: Bruxelles
country: Belgium
facility: Cliniques Universitaire Saint-Luc (Site 058)
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References: