Trial for Relapsed or Refractory AML Patients Combining Cytarabine and Mitoxantrone With Venetoclax (RELAX) (RELAX)
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|ClinicalTrials.gov Identifier: NCT04330820|
Recruitment Status : Recruiting
First Posted : April 2, 2020
Last Update Posted : August 6, 2020
|Condition or disease||Intervention/treatment||Phase|
|Relapsed Adult AML||Drug: Venetoclax Oral Tablet||Phase 1 Phase 2|
- To determine safety, tolerability, maximum tolerated dose, and recommended phase II dose of venetoclax in combination with increasing cytarabine doses plus fixed dose mitoxantrone in subjects with a relapsed or refractory AML considered fit for intensive salvage therapy.
- To assess the preliminary efficacy of venetoclax in combination with increasing cytarabine doses plus fixed dose mitoxantrone in subjects with a relapsed or refractory AML considered fit for intensive salvage therapy.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Sequential Assignment|
|Intervention Model Description:||
The phase I part will be conducted according to the enhanced algorithms of a 3+3H design (Ji et al. J Clin Oncol 2013).
The phase II part will be performed as single stage study adopting the A'Hern design (A'Hern Stat Med 2001).
|Masking:||None (Open Label)|
|Official Title:||Phase-I/II Trial for Relapsed or Refractory AML Patients Combining Cytarabine and Mitoxantrone With Venetoclax (RELAX)|
|Actual Study Start Date :||April 6, 2020|
|Estimated Primary Completion Date :||June 2022|
|Estimated Study Completion Date :||April 2024|
Experimental: Venetoclax+Cytarabin+ Mitoxantron
The treatment plan combines a fixed dose of venetoclax and mitoxantrone with increasing doses of cytarabine (V-MAC).
Drug: Venetoclax Oral Tablet
This study will investigate the combination of a fixed maximum venetoclax dose with increasing cytarabine doses plus mitoxantrone in a fixed dose. The venetoclax dose of 400 mg will be reached by a ramp up over 4 days. Parallel chemotherapy with cytarabine will start on day 4.
Other Name: Cytarabin
- Maximum tolerated dose (= recommended phase II dose) of cytarabine in combination with venetoclax plus mitoxantrone [ Time Frame: appr. 9 months ]number of dose limiting toxicities related to venetoclax per cohort
- CR/CRi rate [ Time Frame: appr. 12 months ]preliminary efficacy of venetoclax in combination with increasing cytarabine doses plus fixed dose mitoxantrone
- remission [ Time Frame: appr. 48 months ]Duration of Remission and Depth of remission (MRD)
- Relapse [ Time Frame: appr. 48 months ]Cumulative incidence of relapse
- Relapse-free survival [ Time Frame: appr. 48 months ]number of participants alive without relapse
- Mortality [ Time Frame: appr. 48 months ]Early mortality (within 14 and 30 days)
- Proportion of allogeneic stem cell transplantation [ Time Frame: appr. 48 months ]number of allogeneic stem cell transplantation following response
- incidence and severity of adverse Events [safety and tolerability] [ Time Frame: appr. 48 months ]number and grade of Adverse Events assessed by CTCAE v5.0
- Overall survival [ Time Frame: appr. 48 months ]number of patients alive
- Identification of biomarkers predicting CR/CRi achievement [ Time Frame: appr. 48 months ]Baseline samples from all patients with be sequenced for genes which have been associated with response to venetoclax treatment. The panel will include TP53, WT1, PDGFRB, ASXL1, and EZH2. Testing for additional markers may be added triggered by new scientific evidence.
- clonal architecture of hematopoiesis [ Time Frame: appr. 48 months ]We will test for changes of the clonal architecture of hematopoiesis during therapy and maintenance treatment. This will be done by NGS using a gene panel including TP53, DNMT3A, ASXL1, TET2, JAK2, RUNX1, SF3B1, and EZH2.
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): NCT04330820
|Contact: Christoph Röllig, Prof. (MD)||+49 351 458 firstname.lastname@example.org|
|Contact: Martin Wermke, MD||+49 351 email@example.com|
|Dresden, Germany, 01307|
|Contact: Christoph Röllig, Prof.|
|Universitätsklinikum Frankfurt am Main||Recruiting|
|Frankfurt am Main, Germany, 60590|
|Contact: Björn Steffen, MD|
|Würzburg, Germany, 97080|
|Contact: Sabrina Kraus, MD|
|Principal Investigator:||Christoph Röllig, Prof. (MD)||Technische Universität Dresden (TUD)|