A Study of Venetoclax in Combination with Azacitidine Versus Azacitidine in previously untreated Subjects with Acute Myeloid Leukemia who are Ineligible for Standard Induction Therapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

AbbVie Deutschland GmbH & Co. KG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

17 Aug 2017 → 15 Sep 2025

Decision date (initial)

2024-07-15

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AbbVie Inc.

External identifiers

EU CT number

2024-513631-25-00

EudraCT number

2016-001466-28

ClinicalTrials.gov

NCT02993523

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacogenetic, Pharmacokinetic, Efficacy, Others, Pharmacodynamic

To evaluate if venetoclax in combination with azacitidine will improve overall survival (OS) and composite complete remission rate (complete remission + complete remission with incomplete marrow recovery; CR/CRi) versus placebo in combination with azacitidine, in treatment naïve subjects with acute myeloid leukemia (AML).

Secondary objectives 3

1. To evaluate if venetoclax in combination with azacitidine will improve, event-free survival (EFS).
2. To evaluate if venetoclax in combination with azacitidine will improve the proportion of subjects achieving composite complete remission (CR or CRi) by the initiation of Cycle 2.
3. To evaluate if venetoclax in combination with azacitidine reduces fatigue and improves global health status/quality of life (GHS/QoL) based on patient reported outcome (PRO) assessments (Patient Reported Outcomes Measurement Information System [PROMIS] Cancer Fatigue Short Form [SF] 7a and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core [EORTC QLQC30]).

Conditions and MedDRA coding

Acute Myeloid Leukemia

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

Yes

IPD plan description

AbbVie is committed to responsible clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information. To learn more about the process, or to submit a request, visit https://www.abbvieclinicaltrials.com/hcp/data-sharing/ For details on when studies are available for sharing, visit https://vivli.org/ourmember/abbvie/

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Subject must have confirmation of AML by WHO criteria and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due age or comorbidities.
2. Female subjects of childbearing potential must have negative results for pregnancy test performed: - At Screening with a serum sample obtained within 14 days prior to the first study drug administration, and - Prior to dosing with urine sample obtained on Cycle 1 Day 1, if it has been > 7 days since obtaining the serum pregnancy test results.
3. Subject must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.
4. Subject must be ≥ 18 years of age.
5. Subject must have a projected life expectancy of at least 12 weeks.
6. Subject must be considered ineligible for induction therapy defined by the following: - ≥ 75 years of age; OR - ≥ 18 to 74 years of age with at least one of the following comorbidities: ● ECOG Performance Status of 2 or 3; ● Cardiac history of CHF requiring treatment or Ejection Fraction ≤ 50% or chronic stable angina; ● DLCO ≤ 65% or FEV1 ≤ 65%; ● Creatinine clearance ≥ 30 mL/min to < 45 ml/min; ● Moderate hepatic impairment with total bilirubin > 1.5 to ≤ 3.0 × ULN; ● Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the AbbVie TA MD before study enrollment.
7. Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status: - 0 to 2 for subjects ≥ 75 years of age OR - 0 to 3 for subjects ≥ 18 to 74 years of age.
8. Subject must have adequate renal function as demonstrated by a creatinine clearance ≥ 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urine collection.
9. Subject must have adequate liver function as demonstrated by: - aspartate aminotransferase (AST) ≤ 3.0 × ULN* - alanine aminotransferase (ALT) ≤ 3.0 × ULN* - bilirubin ≤ 1.5 × ULN* * Unless considered to be due to leukemic organ involvement o Subjects who are < 75 years of age may have a bilirubin of ≤ 3.0 × ULN
10. Female subjects must be either postmenopausal defined as: - Age > 55 years with no menses for 12 or more months without an alternative medical cause - Age ≤ 55 years with no menses for 12 or more months without an alternative medical cause AND an FSH level > 40 IU/L. OR - Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). OR - Women of Childbearing Potential (WOCBP) practicing at least one protocol specified method of birth control, starting at Study Day 1 through at least 90 days after the last dose of study drug.
11. Male subjects who are sexually active, must agree, from Study Day 1 through at least 90 days after the last dose of study drug, to practice the protocol specified contraception. Male subjects must agree to refrain from sperm donation from initial study drug administration through at least 90 days after the last dose of study drug.
12. Subject must currently be receiving venetoclax/placebo and azacitidine in the Main Study and maintain confirmed remission.

Exclusion criteria 15

1. Subject has received treatment with the following: - A hypomethylating agent and/or chemo therapeutic agent for Myelodysplastic syndrome (MDS). - CAR-T cell therapy - Experimental therapies for MDS or AML.
2. Subject has history of myeloproliferative neoplasm (MPN).
3. Subject has the following: - Favorable risk cytogenetics such as t(8;21), inv(16) or t(16;16) or t(15;;17) as per the NCCN Guidelines Version 2, 2016 for Acute Myeloid Leukemia.
4. Subject has acute promyelocytic leukemia
5. Subject has known active CNS involvement with AML.
6. Subject is known to be positive for HIV (HIV testing is not required.)
7. Subject is known to be positive for hepatitis B or C infection with the exception of those with an undetectable viral load within 3 months. (Hepatitis B or C testing is not required). Subjects with serologic evidence of prior vaccination to HBV [i.e., HBs Ag-, and anti-HBs+] may participate.
8. Subject has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
9. Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
10. Subject has a cardiovascular disability status of New York Heart Association Class > 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
11. Subject has 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.
12. Subject has a malabsorption syndrome or other condition that precludes enteral route of administration.
13. Subject exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).
14. Subject has a history of other malignancies within 2 years prior to study entry, 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.
15. Subject has a white blood cell count > 25 × 109/L. (Hydroxyurea is permitted to meet this criterion.)

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Rate of complete remission (CR) or complete remission with incomplete marrow recovery (CRi)
2. Overall Survival (OS)

Secondary endpoints 3

1. Event-Free Survival (EFS)
2. CR + CRi rate by the initiation of Cycle 2
3. Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue Short Form [SF] 7a and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core [EORTC QLQ-C30]).

Investigational products

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

Test 4

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

AbbVie Deutschland GmbH & Co. KG

Sponsor organisation

AbbVie Deutschland GmbH & Co. KG

Address

Knollstrasse

City

Ludwigshafen Am Rhein

Postcode

67061

Country

Germany

Scientific contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Public contact point

Organisation

AbbVie Deutschland GmbH & Co. KG

Contact name

Global Clinical Trials Helpdesk

Third parties 5

Locations

6 EU/EEA countries · 8 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 32 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