Multicenter, Open-Label, Single Arm, Phase II Exploratory Study to Evaluate the Reinduction and Second Stop of TKI with Ponatinib in CML in Molecular Response (ResToP)
Overview
- Phase
- Phase 2
- Intervention
- Ponatinib 15 MG
- Conditions
- Chronic Myeloid Leukemia, Chronic Phase
- Sponsor
- Fundacion CRIS de Investigación para Vencer el Cáncer
- Enrollment
- 80
- Locations
- 13
- Primary Endpoint
- Proportion of patients with a maintained MMR within 52 weeks following ponatinib Treatment-Free Remission (TFR)
- Status
- Active, not recruiting
- Last Updated
- last year
Overview
Brief Summary
The purpose of the present study is to determine the rate of successful treatment-free remission (TFR) within the first 52 weeks following cessation of ponatinib treatment in patients who achieved MR4. Eligible patients had been previously treated with TKI and when patients achieved an optimal molecular response, TKI treatment was discontinued. After loss of response, patients were treated again with a TKI treatment and have documented MR4 for one year at the time of switch to ponatinib to study entry. MR4 is defined as BCR-ABL transcript level ≤ 0.01% IS or undetectable BCR-ABL levels with sample sensitivity of at least 4 log.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Male or female patients ≥ 18 years of age.
- •ECOG Performance Status of 0, 1, or
- •Patient with diagnosis of BCR-ABL positive and Ph+ CML-Chronic Phase.
- •Patients who failed the first attempt of TKI discontinuation and after TKI reintroduction they achieve again MR4 and it is maintained and confirmed for more than one year.
- •Patients who are able to take oral therapy
- •Adequate end organ function as defined by:
- •Direct bilirubin ≤ 1.5 x ULN except for i) patient with documented Gilbert's syndrome for whom any bilirubin value is allowed and ii) for patients with asymptomatic hyperbilirubinemia (liver transaminases and alkaline phosphatase within normal range),
- •SGOT(AST) and SGPT(ALT) ≤ 2.5 x ULN,
- •Serum lipase and amylase ≤ 1.5 x ULN,
- •Alkaline phosphatase ≤ 2.5 x ULN,
Exclusion Criteria
- •Prior accelerate phase, blast crisis or autologous or allogenic transplant.
- •Patients with known atypical transcript. An atypical transcript is defined by the presence of any transcript in the absence of the major transcripts b3a2 (e14a2) and b2a2 (e13a2) or p210 protein.
- •CML treatment resistant mutation(s) (T315I, E255K/V, Y253H, F359C/V) detected if a testing was done in the past (there is no requirement to perform mutation testing at study entry if it was not done in the past).
- •Are taking medications with a known risk of torsades de pointes (Annex 5).
- •Patient ever attempted to permanently discontinue TKI treatment.
- •Severe and/or uncontrolled concurrent medical disease that in the opinion of the investigator could cause unacceptable safety risks or compromise compliance with the protocol (e.g., uncontrolled diabetes (defined as HbA1c \> 9%), uncontrolled infection).
- •Have clinically significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to:
- •Any history of MI, unstable angina, cerebrovascular accident, or TIA.
- •Any history of peripheral vascular infarction, including visceral infarction.
- •Any revascularization procedure, including the placement of a stent.
Arms & Interventions
Ponatinib plus ASA treatment
Patients will be treated with ponatinib 15 mg/day plus 100 mg/day ASA for 104 weeks. After that, ponatinib and ASA will be stopped.
Intervention: Ponatinib 15 MG
Ponatinib plus ASA treatment
Patients will be treated with ponatinib 15 mg/day plus 100 mg/day ASA for 104 weeks. After that, ponatinib and ASA will be stopped.
Intervention: Acetylsalicylic acid 100 MG
Outcomes
Primary Outcomes
Proportion of patients with a maintained MMR within 52 weeks following ponatinib Treatment-Free Remission (TFR)
Time Frame: 52 weeks
This variable is defined as the number of patients who have a maintained MMR and have not restarted TKI therapy in the first 52 weeks after starting ponatinib TFR phase divided by the number of patients who entered ponatinib TFR phase.
Secondary Outcomes
- Evaluate thromboembolic events for study period.(104 weeks)
- Evaluate hemorrhagic events for study period.(104 weeks)
- Evaluate the toxicity and safety profile of 15 mg/24h dose treatment of ponatinib combined with ASA.(104 weeks)
- Evaluate hemolytic events for study period.(104 weeks)
- Evaluate the proportion of patients still in MR4 (BCR-ABL ≤ 0.01%) within 52 weeks following ponatinib therapy cessation.(52 weeks)
- Evaluate the proportion of patients still in MMR within 24 weeks following ponatinib therapy cessation.(24 weeks)
- To estimate progression-free survival (PFS)(4 years)
- Evaluate gastrointestinal events for study period.(104 weeks)
- Treatment-free survival (TFS)(104 weeks)