A Study of Venetoclax Co-Administered with Low Dose Cytarabine Versus Low Dose Cytarabine in Untreated Patients with Acute Myeloid Leukemia Who Are Ineligible for Intensive Chemotherapy

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

24 Oct 2017 → 21 Aug 2025

Decision date (initial)

2024-07-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

AbbVie Inc.

External identifiers

EU CT number

2024-513630-37-00

EudraCT number

2016-003900-30

ClinicalTrials.gov

NCT03069352

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

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

To evaluate if venetoclax when co-administered with low dose cytarabine (LDAC) improves overall survival (OS) versus LDAC and placebo, in treatment naïve subjects with acute myeloid leukemia (AML).

Secondary objectives 5

1. To evaluate if venetoclax when co-administered with LDAC improves complete remission rate (complete remission + complete remission with incomplete marrow recovery, CR + CRi).
2. To evaluate if venetoclax when co-administered with LDAC improves event-free survival (EFS).
3. To evaluate if venetoclax when co-administered with LDAC improves the proportion of subjects achieving a composite CR (CR + CRi) by the end of Cycle 1.
4. To evaluate if venetoclax when co-administered with LDAC reduces fatigue based on patient reported outcome (PRO) assessment Patient Reported Outcomes Measurement Information System (PROMIS), Fatigue Short Form (SF) 7a.
5. To evaluate if venetoclax when co-administered with LDAC improves subjects Global Health Status/Quality of Life (GHS/QoL) based on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30).

Conditions and MedDRA coding

Acute Myeloid Leukemia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 9

1. A subject will be eligible for study participation if he/she meets the following criteria within 21 days prior to randomization. • Subject must have histological confirmation of AML by WHO criteria, is ineligible for intensive induction chemotherapy and either is: - ≥ 75 years of age OR - ≥ 18 to 74 years of age and fulfill at least one criteria associated with lack of fitness for intensive induction chemotherapy: • Eastern Cooperative Oncology Group (ECOG) Performance status of 2 – 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 • Other comorbidity that the physician judges to be incompatible with conventional intensive chemotherapy which must be reviewed and approved by the study medical monitor before study enrollment
2. Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status: • of 0 to 2 for subjects ≥ 75 years of age OR • of 0 to 3 for subjects between 18 to 74 years of age
3. Subject must have a projected life expectancy of at least 12 weeks.
4. 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.
5. 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* o Subjects who are < 75 years of age may have bilirubin of ≤ 3.0 × ULN * Unless considered to be due to leukemic organ involvement.
6. Female subjects must be either postmenopausal defined as: - Age > 55 years with no menses for 12 or more months without an alternative medical cause OR - 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 - A Woman of Childbearing Potential (WOCBP) practicing at least one protocol specified method of birth control starting at Study Day 1 through at least 180 days after the last dose of study drug.
7. Male subjects who are sexually active, must agree, from Study Day 1 through at least 180 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 180 days after the last dose of study drug.
8. Females 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 Week 1 Day 1, if it has been > 7 days since obtaining the serum pregnancy test results. - Subject with borderline pregnancy tests at screening must have a serum pregnancy test ≥ 3 days later to document continued lack of a positive result.
9. Subject must voluntarily sign and date an informed, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

Exclusion criteria 14

1. Subject has received any prior treatment for AML with the exception of hydroxyurea, allowed through the first cycle of study treatment. Note: Prior treatment for Myelodysplastic Syndrome is allowed except for use of cytarabine.
2. Subject had an antecedent myeloproliferative neoplasm (MPN) including myelofibrosis, essential thrombocytosis, olycythemia vera, or chronic myelogenous leukemia (CML) with or without BCR-ABL mutation
3. Subjects that have acute promyelocytic leukemia (APL).
4. Subject has known CNS involvement with AML.
5. Subject has known HIV infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax).
6. Subject is known to be positive for hepatitis B virus (HBV), or hepatitis C virus (HCV) infection. Inactive hepatitis carrier status or low viral hepatitis titer on antivirals (non-exclusionary medications) are not excluded.
7. Subject has received strong or moderate CYP3A inducers 7 days prior to the initiation of study treatment.
8. Subject has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Star fruit within 3 days prior to the initiation of study treatment.
9. Subject has cardiovascular disability status of New York Heart Association Class > 2. Class 2 is defined as cardiac disease which subjects are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or angina pain.
10. 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.
11. Subject has a malabsorption syndrome or other condition that precludes enteral route of administration
12. Subject exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).
13. Subject has a history of other malignancies 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.
14. Subject has a white blood cell count > 25 × 109/L. (Note: Hydroxyurea administration or leukapheresis is permitted to meet this criterion).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall Survival (OS)

Secondary endpoints 4

1. CR + CRi rate
2. CR + CRi rate by initiation of Cycle 2.
3. Patient Reported Outcomes Measurement Information System (PROMIS) Cancer Fatigue Short Form [SF] 7a.
4. Global Health Status/Quality of Life (GHS/QoL) based on the 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 4

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

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

Application history

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