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 - DECIDER-2 trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical Center - University Of Freiburg

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

22 Sep 2022 → ongoing

Decision date (initial)

2024-10-16

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Deutsche Forschungsgemeinschaft (DFG)

External identifiers

EU CT number

2023-507461-26-00

EudraCT number

2020-005495-36

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

To compare the efficacy of all-trans retinoic acid (ATRA) versus placebo as addon to the backbone treatment (DAC and VEN) with respect to overall survival (OS)

Secondary objectives 1

1. to compare all-trans retinoic acid (ATRA) versus placebo as add-on to the backbone treatment (DAC and VEN) with respect to objective best response (complete remission (CR) with or without (CRi) full hematopoietic regeneration, morphologic leukemia-free state (MLFS) or partial remission (PR)), CR with negative measurable residual disease (CRMRD-), probability of survival with objective best response, quality of life, safety.

Conditions and MedDRA coding

Newly diagnosed acute myeloid leukemia (AML)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

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,
5. Patients considered not to benefit from the induction therapy or whom standard induction chemotherapy is not feasible; the following criteria are accepted (example): - age ≥ 75 years - - ECOG ≥ 1 - - HCT-CI ≥ 3 - adverse genetics - - 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

Exclusion criteria 21

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 prescribed by the clinical trial protocol; the patient must have recovered from all clinically relevant reversible non-hematologic toxicities
6. Central nervous system (CNS) leukemia
7. Severe congestive heart failure, clinically unstable cardiac disease or QTc prolongation ≥ CTCAE grade 3
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 (ATRA) 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS) time

Secondary endpoints 4

1. Objective best response (CR, CRi, MLFS or PR)
2. CR with negative MRD (CRMRD-)
3. OS time with objective best response (CR, CRi, MLFS or PR)
4. Quality of life (EORTC QLQ-C30) (especially fatigue) and FACIT Fatigue Scale

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical Center - University Of Freiburg

Sponsor organisation

Medical Center - University Of Freiburg

Address

Breisacher Strasse 153, Mooswald Mooswald

City

Freiburg Im Breisgau

Postcode

79110

Country

Germany

Scientific contact point

Organisation

Medical Center - University Of Freiburg

Contact name

Coordinating Investigator

Public contact point

Organisation

Medical Center - University Of Freiburg

Contact name

Project Management

Third parties 4

Locations

1 EU/EEA country · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

5 submissions — initial application plus substantial / non-substantial modifications