- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02627677
A Study Comparing Ponatinib and Nilotinib in Participants With Chronic Myeloid Leukemia (OPTIC-2L)
A Randomized, Open-label Study of Ponatinib Versus Nilotinib in Patients With Chronic Myeloid Leukemia in Chronic Phase Following Resistance to Imatinib
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 3
Contacts and Locations
Study Locations
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Bruxelles, Belgium, 1200
- Cliniques Universitaire Saint-Luc (Site 058)
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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.
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Ponatinib 30 mg, taken orally once daily.
Other Names:
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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.
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Ponatinib 15 mg, taken orally once daily.
Other Names:
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Active Comparator: Cohort C: Nilotinib 400 mg
Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months.
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Nilotinib 400 mg, taken orally twice daily.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Major Molecular Response (MMR)
Time Frame: Up to 12 months
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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.
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Up to 12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Percentage of Participants With Major Cytogenetic Response (MCyR)
Time Frame: Up to 12 months
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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.
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Up to 12 months
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Percentage of Participants With Complete Cytogenetic Response (CCyR)
Time Frame: Up to 12 months
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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.
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Up to 12 months
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Percentage of Participants With Molecular Response (MR)
Time Frame: From Month 3 to every 3 months up to 48 months
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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.
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From Month 3 to every 3 months up to 48 months
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Percentage of Participants With MR1
Time Frame: Month 3
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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.
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Month 3
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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)
Time Frame: From first dose up to 30 days post last dose (Up to approximately 46 months)
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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.
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From first dose up to 30 days post last dose (Up to approximately 46 months)
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Time to Response
Time Frame: Up to approximately 60 months
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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.
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Up to approximately 60 months
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Duration of Response
Time Frame: Up to approximately 60 months
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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.
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Up to approximately 60 months
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Progression-free Survival (PFS)
Time Frame: Up to end of study (approximately 60 months)
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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.
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Up to end of study (approximately 60 months)
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Overall Survival
Time Frame: Up to end of study (approximately 60 months)
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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.
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Up to end of study (approximately 60 months)
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Percentage of Participants Who Achieved/Maintained Complete Hematologic Response (CHR)
Time Frame: 3 months after the first dose of study treatment
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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).
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3 months after the first dose of study treatment
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Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption
Time Frame: From first dose up to end of treatment (Up to approximately 45 months)
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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.
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From first dose up to end of treatment (Up to approximately 45 months)
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Percentage of Participants With Progression to Accelerated Phase (AP) or Blast Phase (BP)-CML
Time Frame: Up to end of study (Up to approximately 60 months)
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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.
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Up to end of study (Up to approximately 60 months)
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Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Bone Marrow Diseases
- Hematologic Diseases
- Myeloproliferative Disorders
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myelogenous, Chronic, BCR-ABL Positive
- Leukemia, Myeloid, Chronic-Phase
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Protein Kinase Inhibitors
- Ponatinib
Other Study ID Numbers
- AP24534-15-303
- 2015-001318-92 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
- Clinical Study Report (CSR)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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