An open-label, single-arm, pilot study of Venetoclax in combination with 5 days Azacitidine in treatment-naïve subjects with acute myelogenous leukemia who are ≥18 years of age and not eligible for standard induction therapy (VENAZA-5S PILOT TRIAL)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

University of Leipzig

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

16 May 2023 → 16 Nov 2025

Decision date (initial)

2023-03-01

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective of the trial is to generate first data on the efficacy of the combination of Venetoclax and 5-day courses of Azacitidine in the studied patient population in a descriptive manner.

Secondary objectives 7

1. To describe the depth and duration of response with the combination regimen
2. To describe survival with the combination regimen
3. To describe the safety and toxicity profile of the combination regimen
4. To describe potential treatment interruptions and discontinuations
5. To describe potential hospitalizations
6. To describe Quality of life (QoL, EORTC QLQ-C30) with the combination regimen
7. To describe MRD levels on study treatment

Conditions and MedDRA coding

Acute myeloid leukemia

Study design 2 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Confirmed diagnosis of AML by WHO criteria 2016 AND ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to age or comorbidities
2. Age ≥ 18 years
3. Projected life expectancy of at least 12 weeks
4. Adequate renal and liver function

Exclusion criteria 10

1. Prior treatment for AML or MDS with one of the following: HMA, Chemotherapeutic agent, CAR-T cell therapy, Experimental therapies; (NOTE: Prior use of hydroxyurea is allowed)
2. History of myeloproliferative neoplasm (MPN)
3. Diagnosis of acute promyelocytic leukemia (APL)
4. Presence of favorable-risk karyotype abnormalities, i.e. t(15;17), t(8;21), inv(16) or t(16;16)
5. Known active CNS involvement with AML
6. Known to be positive for HIV, Hepatitis B or C
7. Cardiovascular disability status of NYHA > 2
8. Chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or any other medical condition that in the opinion of the investigator would adversely affect his/her participating in this study
9. Evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal)
10. History of other malignancies with the exception of adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome measure is the response rate defined as the rate of CR or CRi after up to 6 cycles of therapy (best response).

Secondary endpoints 12

1. Rate of CR or CRi by the Initiation of Cycle 2
2. Rate of CR with partial hematologic recovery (CRh) after up to 6 cycles of therapy
3. Time from initiation of treatment (C1D1) until achievement of CR or CRi
4. Objective response rate (CR, CRh, CRi, MLFS)
5. Event free survival (EFS)
6. Overall survival (OS)
7. Descriptive assessment of MRD levels on study treatment
8. Time to treatment discontinuation
9. Rate of patients with at least one treatment interruption
10. Delay of subsequent cycles, dose reductions or shortening/interruption of study drug administration
11. Duration of patient hospitalization
12. Quality of life (QoL) measured through EORTC QLQ-C30

Investigational products

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

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

University of Leipzig

Sponsor organisation

University of Leipzig

Address

Ritterstraße 26, Zentrum Zentrum

City

Leipzig

Postcode

04109

Country

Germany

Scientific contact point

Organisation

University of Leipzig

Contact name

Sponsor Representative Prof. Metzeler

Public contact point

Organisation

University of Leipzig

Contact name

Sponsor Representative Prof. Metzeler

Locations

1 EU/EEA country · 10 investigational sites

By country

Investigational sites

Country notifications

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

Oversight and notifications

Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77

Corrective measures 1 · Art. 77 CTR

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

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