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A Study Comparing Ponatinib and Nilotinib in Patients With Chronic Myeloid Leukemia (OPTIC-2L)

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ClinicalTrials.gov Identifier: NCT02627677
Recruitment Status : Active, not recruiting
First Posted : December 11, 2015
Last Update Posted : November 22, 2019
Sponsor:
Information provided by (Responsible Party):
Takeda ( Ariad Pharmaceuticals )

Brief Summary:
The purpose of this study is to compare the efficacy and safety of 2 starting doses of ponatinib compared to nilotinib in patients with imatinib-resistant chronic myeloid leukemia (CML) in chronic phase (CP).

Condition or disease Intervention/treatment Phase
Chronic Phase Chronic Myeloid Leukemia Drug: ponatinib 30 mg QD Drug: ponatinib 15 mg QD Drug: nilotinib 400 mg BID Phase 3

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 patients 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).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 44 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Randomized, Open-label Study of Ponatinib Versus Nilotinib in Patients With Chronic Myeloid Leukemia in Chronic Phase Following Resistance to Imatinib
Actual Study Start Date : December 31, 2015
Estimated Primary Completion Date : January 19, 2020
Estimated Study Completion Date : February 19, 2020


Arm Intervention/treatment
Experimental: Cohort A: ponatinib 30 mg QD
ponatinib 30 mg, taken orally once daily
Drug: ponatinib 30 mg QD
ponatinib 30 mg, taken orally once daily
Other Names:
  • Iclusig
  • AP24534

Experimental: Cohort B: ponatinib 15 mg QD
ponatinib 15 mg, taken orally once daily
Drug: ponatinib 15 mg QD
ponatinib 15 mg, taken orally once daily
Other Names:
  • Iclusig
  • AP24534

Active Comparator: Cohort C: nilotinib 400 mg BID
nilotinib 400 mg, taken orally twice daily
Drug: nilotinib 400 mg BID
nilotinib 400 mg, taken orally twice daily
Other Names:
  • Tasigna
  • AMN107




Primary Outcome Measures :
  1. Major molecular response (MMR) [ Time Frame: By 12 months ]
    The BCR-ABL is a fusion gene, a gene formed when pieces of chromosomes 9 and 22 break off and trade places. The ABL gene from chromosome 9 joins to the BCR gene on chromosome 22, to form the BCR-ABL fusion gene. Transcription is the first step of gene expression, in which a particular segment of DNA is copied into RNA (mRNA) by the enzyme RNA polymerase. MMR is the proportion of patients achieving achieving a ratio of ≤0.1% BCR ABL to ABL transcripts on the international scale (≤0.1% BCR-ABL/ABL[IS]) at any time within 12 months after randomization.


Secondary Outcome Measures :
  1. Major cytogenetic response (MCyR) [ Time Frame: By 12 months ]
    MCyR by 12 months is the proportion of patients 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

  2. Complete cytogenetic response (CCyR) [ Time Frame: By 12 months ]
    CCyR by 12 months is the proportion of patients achieving CCyR by 12 months after randomization.

  3. Molecular response (MR) [ Time Frame: By 24 months ]
    The proportion of patients achieving MR2 (defined as (≤1% BCR-ABL[IS]), MMR, MR4 (defined as ≤0.01% BCR-ABL[IS]), and MR4.5 (defined as ≤0.0032% BCR-ABL[IS]) by 24 months after randomization.

  4. MR1 [ Time Frame: At 3 months ]
    MR1 is the proportion of patients achieving a ratio of ≤10% BCR ABL to ABL transcripts on the international scale at 3 months

  5. Safety: Frequencies of vascular occlusive events (VOEs), adverse events (AEs), and serious AEs (SAEs) [ Time Frame: 60 months ]
    Frequencies of vascular occlusive events (VOEs), adverse events (AEs), and serious AEs (SAEs). VOEs will be categorized as arterial or venous and according to main vasculature affected (cardiovascular, cerebrovascular or peripheral vascular).

  6. Time to response [ Time Frame: By 12 months ]
    Time to MMR is defined as the interval between the randomization date and the first date at which the criteria for response are met

  7. Duration of response [ Time Frame: 60 months ]
    Duration of response is defined as the interval between the first assessment at which the criteria for response are met until the earliest date at which loss of response occurs, or the criteria for progression are met

  8. Progression-free survival [ Time Frame: 60 months ]
    Progression-free survival (PFS) is defined as the interval between the first dose date of study treatment and the first date at which the criteria for progression are met (progression to AP- or BP CML), or death due to any cause, censored at the last response assessment

  9. Overall survival [ Time Frame: 60 months ]
    Overall survival (OS) is 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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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02627677


Locations
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Belgium
Cliniques Universitaire Saint-Luc (Site 058)
Bruxelles, Belgium, 1200
Sponsors and Collaborators
Ariad Pharmaceuticals

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Responsible Party: Ariad Pharmaceuticals
ClinicalTrials.gov Identifier: NCT02627677     History of Changes
Other Study ID Numbers: AP24534-15-303
2015-001318-92 ( EudraCT Number )
First Posted: December 11, 2015    Key Record Dates
Last Update Posted: November 22, 2019
Last Verified: November 2019
Keywords provided by Takeda ( Ariad Pharmaceuticals ):
CML
CP-CML
Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia, Myeloid, Chronic-Phase
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Ponatinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action