Prospective randomized multicenter phase III trial of decitabine and venetoclax administered in combination with all-trans retinoic acid or placebo in patients with acute myeloid leukemia who are ineligible for induction chemotherapy
- Conditions
- C92Myeloid leukaemia
- Registration Number
- DRKS00023646
- Lead Sponsor
- niversitätsklinikum Freiburg
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- All
- Target Recruitment
- 256
1. Age = 18 years
2. Previously untreated AML (WHO 2016)
3. ECOG = 2
4. White blood cell count < 25 × 109/L (hydroxyurea or Ara-C are permitted to meet this criterion see section 6.6.2)
5. No standard induction chemotherapy feasible; the following criteria are generally accepted:
• age = 75 years
• ECOG = 1
• HCT-CI = 3
• patient declines standard aggressive chemotherapy
• missing social support system
6. Projected life expectancy of at least 8 weeks
7. Written informed consent obtained according to international guidelines and local laws
8. Ability to understand the nature, significance and consequences of the trial and the trial related procedures and to comply with them
1. Acute promyelocytic leukemia (APL, FAB M3)
2. Previous treatment with DAC, azacitidine, or other DNA-hypomethylating agents, ATRA, venetoclax and other Bcl-2 inhibitors
3. Previous allogeneic stem cell transplantation or solid organ transplantation
4. Previous induction chemotherapy
5. Previous low-dose chemotherapy (e.g. hydroxyurea, cytosine arabinoside (Ara-C), melphalan etc.) within 4 weeks prior to the first administration of study treatment, except for cytoreduction of leukocytosis = 25,000/µl with hydroxyurea or Ara-C as proscribed by the clinical trial protocol (section 6.6.2); the patient must have recovered from all clinically relevant reversible non-hematologic toxicities
6. Central nervous system (CNS) leukemia
7. Severe congestive heart failure or clinically unstable cardiac disease
8. Known positivity for HIV, Hepatitis B# or Hepatitis C
9. Uncontrolled bacterial, viral or fungal infection
10. Known allergy against soy-beans or peanuts (due to ATRA excipients)
11. Known hypersensitivity to or intolerance of one of the trial drugs or its constituents (e.g. other retinoids or sunset yellow FCF E110)
12. Known rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption
13. Any malignancy requiring chemotherapy for which the patient received chemotherapy within 3 months prior to randomization
14. Participation in any other interventional clinical trial within the last 30 days before randomization
15. Simultaneous participation in other interventional trials which could interfere with this trial; simultaneous participation in registry and diagnostic trials is allowed
16. Patient without legal capacity
17. Known or persistent abuse of medication, drugs or alcohol
18. Active COVID-19-infection or non-compliance with the prevailing hygiene measures regarding the COVID-19 pandemic
19. Person who is in a relationship of dependence/employment with the sponsor or the investigator
20. Current or planned pregnancy, nursing period
21. For fertile patients: failure to use one of the following safe methods of contraception: intra-uterine device or hormonal contraception in combination with a mechanical method of contraception.
Study & Design
- Study Type
- interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Overall survival (OS) time
- Secondary Outcome Measures
Name Time Method • Objective best response (CR, CRi, MLFS or PR)<br>• CR with negative MRD (CRMRD-)<br>• OS time with objective best response (CR, CRi, MLFS or PR) <br>• Quality of life (EORTC QLQ-C30) (especially fatigue) and FACIT Fatigue Scale