Study of the safety and efficacy of treatment venetoclax + azacitidine and donor lymphocyte infusion in patients with MDS or AML in relapse after transplantation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Groupe Francophone Des Myelodysplasies

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

23 Nov 2022 → ongoing

Decision date (initial)

2024-10-07

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AbbVie

External identifiers

EU CT number

2024-514877-23-00

EudraCT number

2021-000632-56

ClinicalTrials.gov

NCT05226455

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

The objectives of this study are to assess the safety, and efficacy, of venetoclax in combination with AZA/DLI in patients with MDS and AML (myeloid neoplasms) in relapse after allogeneic hematopoietic stem cell transplantation.
Phase I:
-Assess the safety profile of venetoclax in combination with AZA/DLI
-Determine the recommended Phase II dose (RPTD)
Phase II:
Determine the efficacy of venetoclax in combination with AZA/DLI

Secondary objectives 5

1. Toxicity as measured by NCI CTCAE 5.0
2. Duration of response
3. Overall survival
4. Progression-free survival
5. Event-free survival

Conditions and MedDRA coding

Myelodysplastic syndromes or Acute Myeloid Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Documented relapse of MDS or AML (with WBC < 15000/mm3) after allo-SCT
2. Age ≥ 18 years
3. Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
4. Patient must have adequate organ function as indicated by the following laboratory values: Serum creatinine < 2 mg/dl OR calculated creatinine clearance ≥ 30 mL/min for patients with creatinine levels > 1.5 x institutional ULN ; Serum total bilirubin ≤ 2.5 x ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels ≥ 2 mg/dL ; AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN ; Alkaline Phosphatase ≤ 5 x ULN (If > 2.5 x ULN, then liver fraction should be ≤ 2.5 x ULN)
5. Patient not refractory to platelet transfusions
6. Female subject of childbearing potential must practice at least one protocol specified method of birth control, starting on Study Day 1 through at least 30 days after the last dose of venetoclax or 6 months after the last dose of azacitidine
7. Male subjects sexually active with female partner(s) of childbearing potential, must agree from first dose of study drug(s) through at least 30 days after the last dose of venetoclax or 3 months after the last dose of azacitidine, whichever is later, to practice the protocol specified contraception
8. Patient is available for periodic blood sampling, study related assessments, and appropriate clinical management at the treating institution for the duration of the study
9. Patient has the ability to understand and willingness to sign an informed consent form indicating the investigational nature of the study
10. Patient is able to swallow capsules

Exclusion criteria 18

1. Patient has active and uncontrolled infection
2. Patient has active acute or chronic GVHD
3. Patient receives more than 1mg/kg/day prednisolone
4. Patient has uncontrolled intercurrent illness or circumstances that could limit compliance with the study, including but not limited to the following: symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, pancreatitis, or psychiatric or social conditions that may interfere with patient compliance
5. Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drug
6. Patient has known human immunodeficiency virus (HIV) infection or HIV-related malignancy
7. Patient has clinically active hepatitis B or hepatitis C infection
8. Patient has a known allergy or hypersensitivity to any component of VENETOCLAX or AZA
9. Patient with a "currently active" second malignancy, other than non-melanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for > 2 years or are considered by their physician to be at less than 30% risk of relapse
10. Patient has received growth factors such as erythropoietin alfa (EPO) or granulocyte colony-stimulating factor (G-CSF) or has received non cytotoxic agents (including low dose oral chemotherapy) in the 30 days before inclusion. In case of previous cytotoxic treatment, an interval of 3 months is required.
11. Patient is on any systemic steroids that have not been stabilized to the equivalent of ≤ 10 mg/day prednisone during the 4 weeks prior to the start of the study drugs
12. Patients with clinical evidence of CNS leukemia
13. Patient has a history of GI surgery or other procedures that might interfere with the absorption or swallowing of the study drugs
14. Subject has received strong or moderate CYP3A inhibitors within 3 days prior to the first dose of study drug
15. Patient is unable to take and/or tolerate oral medications on a continuous basis
16. Patient is pregnant or breastfeeding within the projected duration of the study
17. Subject has a malabsorption syndrome or other condition that precludes an enteral route of administration
18. Absence of social security

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Phase I: To determine toxicity profile and safety of the combination
2. Phase II: Overall hematological response rate of venetoclax in combination with AZA/DLI. Response assessment will be performed for MDS according to IWG criteria and according to European LeukemiaNet criteria for AML.

Secondary endpoints 6

1. Toxicity as measured by NCI CTCAE 5.0
2. Acute and chronic GVHD rate
3. Duration of response
4. Overall survival
5. Progression-free survival
6. Event-free survival

Investigational products

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

Test 3

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Groupe Francophone Des Myelodysplasies

Sponsor organisation

Groupe Francophone Des Myelodysplasies

Address

Opital St Louis Hemato Seniors T4, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris

Postcode

75010

Country

France

Scientific contact point

Organisation

Groupe Francophone Des Myelodysplasies

Contact name

Thomas CLUZEAU

Public contact point

Organisation

Groupe Francophone Des Myelodysplasies

Contact name

Thomas CLUZEAU

Locations

1 EU/EEA country · 16 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 8 files

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

Application history

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