Phase II Study of (Early) Combination Salvage Therapy With Venetoclax and Intensified Decitabine in Relapsed/Refractory AML
Overview
- Phase
- Phase 2
- Intervention
- Decitabine
- Conditions
- AML
- Sponsor
- University Hospital Tuebingen
- Enrollment
- 27
- Locations
- 1
- Primary Endpoint
- Rate of hematological remissions
- Status
- Recruiting
- Last Updated
- last year
Overview
Brief Summary
The goal of this prospective, phase II single center, one arm, open label clinical trial is to test the efficacy and feasibility of a combination salvage therapy with Venetoclax and intensified Decitabine in patients with newly diagnosed AML (acute myeloid leukemia) and primary induction failure and patients with relapse of AML/MDS IB2 (myelodysplastic neoplasm with increased blasts 2) after chemotherapy. The primary endpoint is hematologic remission after treatment with Decitabine and Venetoclax. Participants eligible for the trial will receive a treatment of ten days of Decitabine and twenty-eight days of Venetoclax for one or two cycles, after which hematological remission will be assessed. Follow up will include the first one hundred days after end of treatment.
Detailed Description
This is a prospective, phase II single center one arm, open label clinical trial testing the efficacy and feasibility of a combination salvage therapy with Venetoclax and intensified Decitabine in relapsed or refractory AML and MDS IB2. Enrolled will be twenty-seven patients with newly diagnosed AML and primary induction failure to conventional anthracycline-based induction chemotherapy, as well as patients with a relapse of AML oder MDS IB2 after chemotherapy. Patients will receive a combination therapy of ten days of Decitabine and twenty-eigt days of Venetoclax. If hematologic remission is not achieved after one cycle of treatment, patients receive a second cycle. After treatment, a follow-up period of 100 days will ensue. The main aim of the trial is the assessment of hematologic remission after combining Venetoclax with a time-dense immediate application of the hypomethylating agent Decitabine after failure of a chemotherapy approach, thus additionally altering backbone treatment modalities from chemotherapy to epigenetic and anti-BCL2 (B-cell lymphoma 2) treatment. A first assessment of safety and feasibility will take place after the treatment of three patients and a second assessment for safety, feasibility and efficacy/futility after nine patients.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment
Salvage therapy with Venetoclax and intensified Decitabine
Intervention: Decitabine
Treatment
Salvage therapy with Venetoclax and intensified Decitabine
Intervention: Venetoclax
Outcomes
Primary Outcomes
Rate of hematological remissions
Time Frame: measured after the first and second cycle (each cycle is 28 days)
Hematologic remission (defined as morphologically leukemia-free state (MLFS), complete remission (CR), complete remission with incomplete hematological recovery (CRi) or complete remission with partial hematological recovery (CRh)) as best response in bone marrow aspiration cytomorphology\*) after one or two cycles of Decitabine/Venetoclax. \* or bone marrow pathology, if aspiration morphology not available, not representative or not judged sufficiently reliable by treating physician
Secondary Outcomes
- Overall survival(day 100 after end of treatment)
- Early Mortality(day 30 after start of treatment)
- Rate of CTCAEs ≥ Grade 3(observed during the first and second cycle (each cycle is 28 days) and until day 30 after therapy application)
- Time to hematopoietic recovery in days(after each chemotherapy treatment cycle (28 days), defined as the time from the start of the cycle until recovery)
- Rate of MRD-negativity (measurable residual disease)(measured at each remission assessment (C1D15, C1D28, C2D28, Follow Up))
- Rate of infectious complications CTCAEs ≥ grade 3(measured during the first and second cycle and the first 30 days after end of treatment (each cycle is 28 days))
- Time to transplant in days(until day 100 after end of treatment)
- Progression-free survival(day 100 after end of treatment)
- Quality of Life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30))(at screening and at the end of cycle one and two (one cycle is 28 days) and at follow up (day 100 after end of treatment))
- Hospitalisation days(Day 1 of therapy until day 30 after end of treatment)
- ECOG prior to start of conditioning for transplant(between end of treatment and follow up)