Chronic Phase Chronic Myeloid LeukemiaPhase 3OPTIC-2LNCT02627677
A Study Comparing Ponatinib and Nilotinib in Participants With Chronic Myeloid Leukemia
A Phase 3 study testing Ponatinib 30 mg QD, Ponatinib 15 mg QD and Nilotinib 400 mg BID in people with Chronic Phase Chronic Myeloid Leukemia, run by Ariad Pharmaceuticals at 1 site in Belgium.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Phase Chronic Myeloid Leukemia
- What is being tested?
- Ponatinib 30 mg QD, Ponatinib 15 mg QD and Nilotinib 400 mg BID
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 44 participants
- Where
- 1 siteBelgium
- Study dates
- 31 Dec 2015to 20 Jan 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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.
Who cannot join
- 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)
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized, Open-label Study of Ponatinib Versus Nilotinib in Patients With Chronic Myeloid Leukemia in Chronic Phase Following Resistance to Imatinib
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).
Read the 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
- Being tested
- Ponatinib 30 mg QD, Ponatinib 15 mg QD, Nilotinib 400 mg BID
- 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
- Medical subject headings
- Leukemia, Myeloid, Chronic-Phase, Leukemia, Leukemia, Myeloid, Leukemia, Myelogenous, Chronic, BCR-ABL Positive, Neoplasms by Histologic Type, Neoplasms, Myeloproliferative Disorders, Bone Marrow Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ponatinib 30 mg QDDrug
Also called Iclusig, AP24534
Ponatinib 30 mg, taken orally once daily.
Ponatinib 15 mg QDDrug
Also called Iclusig, AP24534
Ponatinib 15 mg, taken orally once daily.
Nilotinib 400 mg BIDDrug
Also called Tasigna, AMN107
Nilotinib 400 mg, taken orally twice daily.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: Ponatinib 15 mg QD |
| Cohort C: Nilotinib 400 mg | Active comparator | Nilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months. Receives: Drug: Nilotinib 400 mg BID |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 12 months
Secondary outcomes (12)
Percentage of Participants With Major Cytogenetic Response (MCyR)
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.
Measured: Up to 12 months
Percentage of Participants With Complete Cytogenetic Response (CCyR)
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.
Measured: Up to 12 months
Percentage of Participants With Molecular Response (MR)
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.
Measured: From Month 3 to every 3 months up to 48 months
Percentage of Participants With MR1
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.
Measured: 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)
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.
Measured: From first dose up to 30 days post last dose (Up to approximately 46 months)
Time to Response
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.
Measured: Up to approximately 60 months
Duration of Response
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.
Measured: Up to approximately 60 months
Progression-free Survival (PFS)
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.
Measured: Up to end of study (approximately 60 months)
Overall Survival
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.
Measured: Up to end of study (approximately 60 months)
Percentage of Participants Who Achieved/Maintained Complete Hematologic Response (CHR)
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).
Measured: 3 months after the first dose of study treatment
Percentage of Participants With Treatment Emergent AEs Leading to Treatment Discontinuation, Dose Reduction and Dose Interruption
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.
Measured: From first dose up to end of treatment (Up to approximately 45 months)
Percentage of Participants With Progression to Accelerated Phase (AP) or Blast Phase (BP)-CML
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.
Measured: Up to end of study (Up to approximately 60 months)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Dec 2015 (estimated)
- Study start31 Dec 2015
- Primary completion29 Oct 2020
- Study completion20 Jan 2021
Why it stopped: The study was stopped due to operational feasibility and not due to any safety concerns
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Phase Chronic Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ariad Pharmaceuticals
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Study Director, Study director, Takeda
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02627677
- Sponsor's protocol ID
- AP24534-15-303
- Other IDs
- 2015-001318-92, 2015
- Acronym
- OPTIC-2L
- Status last verified
- Oct 2021
- First submitted
- 13 Aug 2015
- Last updated
- 26 Nov 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
Study at a glance
From the registry record, last updated by the sponsor on 26 Nov 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Open-label Study of Ponatinib Versus Nilotinib in Patients With Chronic Myeloid Leukemia in Chronic Phase Following Resistance to Imatinib
- ClinicalTrials.gov ID
- NCT02627677
- Acronym / sponsor ID
- OPTIC-2L / AP24534-15-303
- 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
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was stopped due to operational feasibility and not due to any safety concerns
- Enrolment
- 44 participants (actual)
- Lead sponsor
- Ariad PharmaceuticalsIndustry (pharma, biotech, devices)
- Study start
- 31 Dec 2015 (actual)
- Primary completion
- 29 Oct 2020 (actual)
- Study completion
- 20 Jan 2021 (actual)
- First posted
- 11 Dec 2015 (estimated)
- Results
- Posted 26 Nov 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Cohort A: Ponatinib 30 mg | Experimental | Drug: Ponatinib 30 mg QDPonatinib 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. |
| Cohort B: Ponatinib 15 mg | Experimental | Drug: Ponatinib 15 mg QDPonatinib 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. |
| Cohort C: Nilotinib 400 mg | Active comparator | Drug: Nilotinib 400 mg BIDNilotinib 400 mg, tablets, orally, twice daily up to approximately 42 months. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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:
- Have adequate hepatic function as defined by all of the following criteria:
Key exclusion criteria (10 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ponatinib 30 mg QDAlso: Iclusig, AP24534Ponatinib 30 mg, taken orally once daily. | Drug | Cohort A: Ponatinib 30 mg |
| Ponatinib 15 mg QDAlso: Iclusig, AP24534Ponatinib 15 mg, taken orally once daily. | Drug | Cohort B: Ponatinib 15 mg |
| Nilotinib 400 mg BIDAlso: Tasigna, AMN107Nilotinib 400 mg, taken orally twice daily. | Drug | Cohort C: Nilotinib 400 mg |
Primary outcome
Percentage of Participants With Major Molecular Response (MMR)
Time frame: Up to 12 months
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.
12 secondary outcomes
Percentage of Participants With Major Cytogenetic Response (MCyR)
Time frame: Up to 12 months
Percentage of Participants With Complete Cytogenetic Response (CCyR)
Time frame: Up to 12 months
Percentage of Participants With Molecular Response (MR)
Time frame: From Month 3 to every 3 months up to 48 months
Percentage of Participants With MR1
Time frame: 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)
Time frame: From first dose up to 30 days post last dose (Up to approximately 46 months)
Time to Response
Time frame: Up to approximately 60 months
Duration of Response
Time frame: Up to approximately 60 months
Progression-free Survival (PFS)
Time frame: Up to end of study (approximately 60 months)
Overall Survival
Time frame: Up to end of study (approximately 60 months)
Percentage of Participants Who Achieved/Maintained Complete Hematologic Response (CHR)
Time frame: 3 months after the first dose of study treatment
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)
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Nov 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. Takeda provides access to the de-identified individual participant data (IPD) for eligible studies to aid qualified researchers in addressing legitimate scientific objectives (Takeda's data sharing commitment is available on https://clinicaltrials.takeda.com/takedas-commitment?commitment=5). These IPDs will be provided in a secure research environment following approval of a data sharing request, and under the terms of a data sharing agreement.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Study Director study director
Takeda
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ponatinib 30 mg QD, Ponatinib 15 mg QD and Nilotinib 400 mg BID in people with Chronic Phase Chronic Myeloid Leukemia, run by Ariad Pharmaceuticals at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Nov 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants With Major Molecular Response (MMR) (time frame: Up to 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Nov 2021.