Ponatinib for Chronic Myeloid Leukemia

(OPTIC Trial)

No longer recruiting at 106 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: Ariad Pharmaceuticals
Must be taking: Tyrosine kinase inhibitors
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 3 JurisdictionsThis treatment is already approved in other countries

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ponatinib, a medication, to evaluate its effectiveness for people with chronic myeloid leukemia (CML) who have not responded to other treatments or have a specific genetic mutation. The study examines three different doses of ponatinib to identify the most effective option. It seeks participants who have tried at least two other therapies without success or have the T315I mutation in their leukemia. As a Phase 2 trial, this research measures ponatinib's effectiveness in an initial, smaller group, offering participants a chance to potentially benefit from a promising treatment.

Do I need to stop my current medications for the trial?

The trial requires that you stop taking any approved tyrosine kinase inhibitors (TKIs) or investigational agents at least 2 weeks before starting the study drug. Other medications like interferon, cytarabine, or immunotherapy must be stopped 14 days prior, and any cytotoxic chemotherapy or radiotherapy must be stopped 28 days before the trial.

Is there any evidence suggesting that ponatinib is likely to be safe for humans?

Research has shown that ponatinib is generally effective, though some safety concerns exist. In past studies, serious side effects were reported. For instance, one study found that 9% of patients experienced life-threatening side effects, such as blood vessel issues, infections, and severe bleeding.

Other studies have identified blood-related side effects, including low platelet levels (cells that help blood clot), low white blood cell counts (which fight infections), and anemia (low red blood cells). Despite these risks, real-world data from Belgium suggested that ponatinib is relatively safe for treating certain types of leukemia. This indicates that while risks are present, many patients tolerate the treatment well.

Ponatinib has already received approval for certain conditions, indicating that its safety is well-studied. However, it is important to weigh both the benefits and risks before joining a trial. Always consult a healthcare provider to determine if this treatment is suitable.12345

Why are researchers excited about this study treatment for chronic myeloid leukemia?

Researchers are excited about ponatinib for chronic myeloid leukemia (CML) because it targets the BCR-ABL1 fusion protein, which is a key driver of this cancer. Unlike standard treatments like imatinib, dasatinib, and nilotinib, ponatinib is effective against mutations that make CML resistant to these drugs, especially the T315I mutation. Ponatinib's ability to inhibit a broader range of mutations offers hope for patients who have exhausted other options, providing a critical alternative in the fight against CML.

What evidence suggests that ponatinib could be an effective treatment for chronic myeloid leukemia?

Research has shown that ponatinib effectively treats chronic myeloid leukemia (CML), particularly in patients unresponsive to other treatments. One study found that ponatinib led to strong and lasting improvements in patients who had tried other drugs before. In this trial, participants will receive different doses of ponatinib: Cohort A will receive 45 mg, Cohort B will receive 30 mg, and Cohort C will receive 15 mg. Previous studies have shown good results with varying doses, with many patients experiencing a major reduction in cancer markers in their blood. These findings support ponatinib as a promising option for people with CML who have limited treatment choices.678910

Who Is on the Research Team?

SD

Study Director Clinical Science

Principal Investigator

Takeda

Are You a Good Fit for This Trial?

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).
See 11 more

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.
See 18 more

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.
How Is the Trial Designed?
3Treatment groups
Experimental Treatment
Group I: Cohort C: Ponatinib 15 mgExperimental Treatment1 Intervention
Group II: Cohort B: Ponatinib 30 mgExperimental Treatment1 Intervention
Group III: Cohort A: Ponatinib 45 mgExperimental Treatment1 Intervention

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

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Approved in United States as Iclusig for:
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Approved in European Union as Iclusig for:
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Approved in Canada as Iclusig for:

Find a Clinic Near You

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 profile image

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber profile image

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Citations

final 5-year results of the phase 2 PACE trial - PubMed CentralPonatinib continued to provide deep, durable responses in heavily pretreated patients with CP-CML. Tolerability was acceptable in this heavily pretreated ...
CML OPTIC Trial Results for ICLUSIG® (ponatinib)Results from OPTIC demonstrate a benefit in a highly-resistant CP-CML population across dosing cohorts. However, optimal benefit:risk outcomes occurred in the ...
3.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/37973457/
Long-Term Follow-Up in Patients With Chronic Myeloid ...The estimated 2-year progression-free survival (PFS) was 84%. Ponatinib dose was reduced during treatment in 22 patients; nevertheless, MMR was ...
A Retrospective Analysis of Ponatinib-Based Therapy in ...Pts who are bridged to ASCT have the best outcomes (2-year OS 71%). However, outcomes are dismal after failure of ponatinib, highlighting the ...
Results of ponatinib as frontline therapy for chronic myeloid ...In a phase 1 trial, ponatinib was effective in patients with chronic myeloid leukemia (CML) or Ph-positive acute lymphoblastic leukemia (ALL) ...
Safety Profile of ICLUSIG (ponatinib) in the PACE trialFatal adverse reactions occurred in 9% of patients who received ICLUSIG; the most frequent fatal adverse reactions were AOEs (2%), sepsis (1.6%), and hemorrhage ...
ICLUSIG | Promotional Material | 9.9.2025Increased Toxicity in Newly Diagnosed Chronic Phase CML: In a prospective randomized clinical trial in the first-line treatment of newly ...
Hematologic safety data of single-agent ponatinib from a ...Hematologic adverse effects analyzed included thrombocytopenia, neutropenia, anemia and arterial thrombotic events. Results: See Table below for ...
Efficacy and Safety of Ponatinib in CML and Ph+ ALL ...Real-world evidence from this Belgian registry shows that ponatinib has a favorable efficacy and safety profile in, and supports its use in CML and Ph+ ALL ...
Ponatinib (Iclusig®) Patient ManagementSafety and efficacy data of ponatinib in patients with CML or. Ph+ ALL was first demonstrated in a single-arm, open-label, international, and ...
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