Ponatinib for Chronic Myeloid Leukemia

(OPTIC Trial)

Recruiting at 85 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ariad Pharmaceuticals

Must be taking: Tyrosine kinase inhibitors

Must not be taking: Torsades de Pointes drugs

Disqualifiers: Cardiovascular disease, Hypertension, Diabetes, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 58

283 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to characterize the efficacy of ponatinib administered in 3 starting doses (45 mg, 30 mg, and 15 mg daily) in participants with CP-CML who are resistant to prior tyrosine-kinase inhibitor (TKI) therapy or have T315I mutation, as measured by \<=1 % Breakpoint Cluster Region-Abelson Transcript Level using International Scale (BCR-ABL1IS) at 12 months.

Research Team

Study Director Clinical Science

Principal Investigator

Takeda

Eligibility Criteria

This trial is for adults with chronic phase chronic myeloid leukemia (CP-CML) who have tried at least two tyrosine kinase inhibitors without success or have a specific mutation (T315I). Participants must be in good health otherwise, with proper liver, kidney, and pancreatic function, no major heart issues, and not pregnant. They should also agree to use effective contraception.

Inclusion Criteria

Provide written informed consent.

Have normal QT interval corrected (Frederica) (QTcF) interval on screening electrocardiogram (ECG) evaluation.

Have a negative pregnancy test documented prior to enrollment (for females of childbearing potential).

Exclusion Criteria

I have a bleeding disorder not caused by my leukemia.

I had a stem cell transplant less than 60 days ago and am experiencing or being treated for graft-versus-host disease.

Have active CNS disease as evidenced by cytology or pathology.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Main Treatment

Participants receive ponatinib at one of three starting doses (45 mg, 30 mg, or 15 mg) daily in 28-day cycles until specific response criteria or up to 24 cycles

24 months

Monthly visits for each 28-day cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

Final visit 30 days after last dose

Optional Treatment Continuation

Participants may enter an optional treatment continuation period following completion of the main treatment period or early withdrawal

Long-term

Treatment Details

Interventions

• Ponatinib

Trial Overview The study tests three different starting doses of ponatinib (45 mg, 30 mg, and 15 mg daily) to see how well they work in patients resistant to previous treatments or those with the T315I mutation. The goal is to achieve a very low level of cancer cells after one year as measured by a specific lab test.

Participant Groups

Group I: Cohort C: Ponatinib 15 mg Experimental Treatment 1 Intervention

Participants received ponatinib 15 mg orally once daily up to data cut-off: 31 May 2020 in each 28 day Cycle.

Group II: Cohort B: Ponatinib 30 mg Experimental Treatment 1 Intervention

Ponatinib 30 mg orally once daily in each 28 day Cycle until achievement of ≤1% BCR-ABL1IS. Once ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.

Group III: Cohort A: Ponatinib 45 mg Experimental Treatment 1 Intervention

Ponatinib 45 mg orally once daily in each 28-day cycle until achievement of ≤1% BCR-ABL1IS up to data cut-off: 31 May 2020. Once ≤1% BCR-ABL1IS was achieved, participants received reduced dose of ponatinib 15 mg orally once daily.

Ponatinib is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Iclusig for:

• Chronic myeloid leukemia (CML)
• Acute lymphoblastic leukemia (ALL)

Approved in European Union as Iclusig for:

• Chronic myeloid leukemia (CML)
• Acute lymphoblastic leukemia (ALL)

Approved in Canada as Iclusig for:

• Chronic myeloid leukemia (CML)
• Acute lymphoblastic leukemia (ALL)

Who Is Running the Clinical Trial?

Ariad Pharmaceuticals

Lead Sponsor

Trials

37

Recruited

3,900+

Takeda

Lead Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier