50 Participants Needed

Ponatinib for Chronic Myeloid Leukemia

JC
EJ
Overseen ByElias Jabbour, MD
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 2 JurisdictionsThis treatment is already approved in other countries

Trial Summary

Will I have to stop taking my current medications?

Participants must stop taking bosutinib, dasatinib, nilotinib, or other anti-leukemia therapies (except hydroxyurea) at least 48 hours before starting the study treatment.

What data supports the effectiveness of the drug Ponatinib for treating Chronic Myeloid Leukemia?

Ponatinib has shown effectiveness in treating Chronic Myeloid Leukemia (CML) by achieving major responses in over half of patients with chronic-phase CML and significant responses in those with more advanced phases, even when other treatments failed. It is particularly effective against a specific mutation (T315I) that makes the disease resistant to other drugs.12345

What safety information is available for Ponatinib in humans?

Ponatinib, also known as Iclusig, has been associated with serious safety concerns, including cardiovascular events (heart-related issues) and arterial occlusive events (blockages in arteries). It was temporarily withdrawn from the market due to these risks but was reintroduced with revised warnings and precautions. Common side effects include pancreatitis (inflammation of the pancreas), hypertension (high blood pressure), hyperlipidemia (high levels of fats in the blood), and liver dysfunction.24678

How is the drug Ponatinib different from other treatments for chronic myeloid leukemia?

Ponatinib is unique because it is specifically designed to target the T315I mutation in the ABL kinase domain, which makes it effective against chronic myeloid leukemia that is resistant to other treatments. It is an oral medication that inhibits multiple tyrosine kinases, including BCR-ABL and FGFRs, and is used when other tyrosine kinase inhibitors are not effective or suitable.1391011

What is the purpose of this trial?

This phase II trial studies how well ponatinib hydrochloride works as second line therapy in treating patients with chronic myeloid leukemia in chronic phase that has not responded to initial treatment (first line) with imatinib mesylate, dasatinib, or nilotinib or cannot tolerate imatinib mesylate, dasatinib, or nilotinib. Ponatinib hydrochloride may stop or control the growth of cancer cells by blocking a protein needed for cell growth.

Research Team

Elias Jabbour | MD Anderson Cancer Center

Elias Jabbour, MD

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

This trial is for patients with chronic myeloid leukemia in the chronic phase who didn't respond to or can't tolerate initial treatments like imatinib mesylate, dasatinib, or nilotinib. Participants must have normal organ function tests, be able to consent, and not be pregnant or breastfeeding. They should also have no severe heart disease, uncontrolled high blood pressure, psychiatric disorders, history of certain cardiovascular events, pancreatitis or more than one prior treatment with FDA-approved TKIs.

Inclusion Criteria

I can care for myself and perform daily activities.
My leukemia is in the early stage and tests positive for specific genetic markers.
My organs are functioning well.
See 6 more

Exclusion Criteria

My high blood pressure is not under control.
Active, uncontrolled psychiatric disorders
My chronic myeloid leukemia is in an advanced stage.
See 14 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ponatinib hydrochloride as second line therapy for chronic myeloid leukemia in chronic phase

Up to 5 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

  • Ponatinib Hydrochloride
Trial Overview The trial is testing ponatinib hydrochloride as a second line therapy for chronic myeloid leukemia that's resistant or intolerant to first-line drugs. It includes laboratory biomarker analysis and quality-of-life assessments to see if this drug can control cancer cell growth by blocking proteins needed for their proliferation.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Ponatinib hydrochlorideExperimental Treatment3 Interventions
Patients receive ponatinib hydrochloride PO QD. Treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.

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

🇺🇸
Approved in United States as Iclusig for:
  • Chronic myeloid leukemia
  • Philadelphia chromosome-positive acute lymphoblastic leukemia
🇪🇺
Approved in European Union as Iclusig for:
  • Chronic myeloid leukemia
  • Philadelphia chromosome-positive acute lymphoblastic leukemia

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Findings from Research

Ponatinib is an effective treatment for adults with T315I-positive chronic myeloid leukaemia (CML) and Philadelphia chromosome-positive acute lymphoblastic leukaemia (ALL), showing major cytogenetic responses in over 50% of chronic-phase CML patients within 12 months and significant responses in accelerated and blast phases as well.
Despite its efficacy, ponatinib carries serious risks, including vascular occlusion and heart failure, leading to FDA warnings, so clinicians must carefully weigh the benefits against these potential adverse effects before prescribing.
Ponatinib: a review of its use in adults with chronic myeloid leukaemia or Philadelphia chromosome-positive acute lymphoblastic leukaemia.Hoy, SM.[2021]
Ponatinib is an effective third-generation tyrosine kinase inhibitor for chronic myeloid leukaemia (CML) patients who are resistant or intolerant to other treatments, showing efficacy even in heavily treated patients.
While ponatinib can induce cardiovascular events, a potential reduction in the starting dose to 15 mg/day may enhance safety without compromising its effectiveness, highlighting the importance of careful patient management during treatment.
Insights into the optimal use of ponatinib in patients with chronic phase chronic myeloid leukaemia.Molica, M., Scalzulli, E., Colafigli, G., et al.[2020]
Ponatinib is an effective treatment for Philadelphia chromosome-positive leukemias that are resistant or intolerant to other therapies, but its use is associated with significant cardiovascular risks, including hypertension and thrombotic events.
To safely use ponatinib, especially in high-risk patients, collaboration between hematologists and cardiologists is essential for monitoring and risk mitigation strategies, ensuring the best outcomes for patients.
Identification, prevention and management of cardiovascular risk in chronic myeloid leukaemia patients candidate to ponatinib: an expert opinion.Breccia, M., Pregno, P., Spallarossa, P., et al.[2017]

References

Ponatinib: a review of its use in adults with chronic myeloid leukaemia or Philadelphia chromosome-positive acute lymphoblastic leukaemia. [2021]
Insights into the optimal use of ponatinib in patients with chronic phase chronic myeloid leukaemia. [2020]
Identification, prevention and management of cardiovascular risk in chronic myeloid leukaemia patients candidate to ponatinib: an expert opinion. [2017]
Resistant mutations in CML and Ph(+)ALL - role of ponatinib. [2022]
Absorption, metabolism, and excretion of [14C]ponatinib after a single oral dose in humans. [2022]
Ponatinib Drives Cardiotoxicity by S100A8/A9-NLRP3-IL-1β Mediated Inflammation. [2023]
FDA Approval Summary: Revised Indication and Dosing Regimen for Ponatinib Based on the Results of the OPTIC Trial. [2022]
Dose optimisation of ponatinib in chronic phase chronic myeloid leukemia. [2023]
Efficacy of ponatinib against ABL tyrosine kinase inhibitor-resistant leukemia cells. [2013]
10.United Statespubmed.ncbi.nlm.nih.gov
Ponatinib (AP24534), a multitargeted pan-FGFR inhibitor with activity in multiple FGFR-amplified or mutated cancer models. [2020]
Management of ponatinib dosing in chronic myeloid leukemia patients. [2022]
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