Ponatinib in Adult Ph+ ALL Patients With MRD Positivity or Hematological Relapse
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|ClinicalTrials.gov Identifier: NCT04475731|
Recruitment Status : Not yet recruiting
First Posted : July 17, 2020
Last Update Posted : January 5, 2021
|Condition or disease||Intervention/treatment||Phase|
|Philadelphia-Positive ALL Acute Lymphoblastic Leukemia, in Relapse||Drug: Ponatinib||Phase 2|
This is a phase II interventional multicenter study for adult patients with Ph+ALL who:
- Are MRD+ (i.e. BCR-ABL1/ABL1 >0.01) (or loose their molecular response) after whichever kind of previous treatment. MRD positivity is indeed regarded as a relapse/resistance, since it represents the early recognition of cases who will eventually experience an hematologic recurrence of disease.
- Are in hematologic relapse after whichever kind of previous treatment.
- Have never achieved an hematologic remission at least after one month of treatment.
Patients will be treated with Ponatinib at a dose of 45 mg/die per os for 28 days for 3 cycles and - if in hematologic and extra-hematologic relapse/refractoriness, clinically fit and according to medical decision - with concurrent systemic chemotherapy. In case of CMR achievement, dosing will be reduced to 30 mg. In case of toxicity, Ponatinib will be reduced to 30 (or 15) mg daily.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||67 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Ponatinib for the Management of Minimal Residual Disease (MRD) and Hematologic Relapse in Adult Ph+ Acute Lymphoblastic Leukemia (Ph+ ALL) Patients|
|Estimated Study Start Date :||February 2021|
|Estimated Primary Completion Date :||November 2022|
|Estimated Study Completion Date :||November 2024|
Experimental: Experimental arm
MRD+ Ph+ ALL adult patients will receive Ponatinib x 4 weeks x 3 courses; +/-Concomitant chemotherapy (according to hematologic status).
Patients will receive the study drug until disease relapse or progression.
Ponatinib 45 mg/day x 4 weeks x 3 courses.
- MRD negativity/reduction rate [ Time Frame: After 3 months of treatment ]Rate of patients who achieve a MRD negativity/MRD reduction following treatment with either Ponatinib alone or in combination with systemic chemotherapy
- Duration of CMR [ Time Frame: at 24 months ]Duration of the CMR status after 3 months of ponatinib treatment
- Hematologic remission rate [ Time Frame: at 24 months ]The achievement of an hematologic remission in patients treated for an hematologic and extra-hematoloigc relapse and for a refractory disease.
- Best molecular response [ Time Frame: at 24 months ]Best molecular response achieved during the follow-up
- Rate of AE/SAEs [ Time Frame: at 24 months ]Safety profile in terms of incidence of grade >3 CTC-NCI side effects and toxicities (AE/SAEs).
- Mutational analysis [ Time Frame: at 24 months ]Mutational analysis in terms of occurrence, type and number of BCR-ABL1 kinase domain mutations.
- Correlation between biological and MRD parameters [ Time Frame: at 24 months ]Correlation between the achievement and duration of CMR (or MRD reduction) with the type of fusion protein (e.g. p190 or p210) and the potential occurrence of mutations, as well as with additional genomic lesions.
- Disease free survival [ Time Frame: 24 months ]Time interval between the achievement of CHR after three months of ponatinib and hematologic relapse of the disease or death in CHR; patients still alive, in CHR.
- Overall survival [ Time Frame: 24 months ]Time interval between treatment start and death for any cause.
- Cumulative incidence of relapse [ Time Frame: 24 months ]Time interval between achievement of CHR after three months of ponatinib until the date of first hematologic relapse of the disease.
- Role of hematological profile on survival outcome [ Time Frame: at 24 months ]Identification of hematological profile on survival outcome
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): NCT04475731
|Contact: Paola Fazifirstname.lastname@example.org|
|Contact: Enrico Creaemail@example.com|