A Phase 1/2 Study of Venetoclax in Combination with Low-Dose Cytarabine in Treatment-Naïve Subjects with Acute Myelogenous Leukemia Who Are = 60 Years of Age and Who Are Not Eligible for Standard Anthracycline-Based Induction Therapy

Phase 1

• Conditions: Acute Myelogenous Leukemia; MedDRA version: 20.0Level: LLTClassification code 10001941Term: AMLSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-002610-23-DE
• Lead Sponsor: AbbVie Deutschland GmbH & Co. KG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2014-09-24
• Last Update Posted: 28 March 2022

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 91

Inclusion Criteria

1. 1. Subject must be = 65 years of age in Phase 1 and initial Phase 2.
Subjects enrolled in Phase 2 Cohort C must be either:
- = 75 years of age;
OR
- = 60 to 74 years will be eligible if the subject has at least one of the following co-morbidities, which make the subject unfit for intensive chemotherapy:
o ECOG Performance Status of 2 – 3;
o Cardiac history of CHF requiring treatment or Ejection Fraction = 50% or chronic stable angina;
o DLCO = 65% or FEV1 = 65%;
o Creatinine clearance = 30 mL/min to < 45 mL/min (calculated by
Cockcroft-Gault formula);
o Moderate hepatic impairment with total bilirubin > 1.5 to = 3.0 ×ULN;
o Any other comorbidity that the physician judges to be incompatible
with intensive chemotherapy must be reviewed and approved by the
study medical monitor before study enrollment..
2. Subject must have a projected life expectancy of at least 12 weeks.
3. Subject must have histological confirmation of AML and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors.
4. Subject must have received no prior treatment for AML with the exception of hydroxyurea, allowed through first cycle of treatment. NOTE: Subject may have been treated for prior Myelodysplastic Syndrome.
5. Subject must have adequate renal function as demonstrated by a creatinine clearance = 30 mL/min; determined via urine collection for 24-hour creatinine clearance.
6. Subject must have adequate liver function as demonstrated by:
- aspartate aminotransferase (AST) = 2.5 × ULN*
- alanine aminotransferase (ALT) = 2.5 × ULN*
- bilirubin = 1.5 × ULN for subjects who are < 75 years of age must have a bilirubin of < 3.0 × ULN
*Unless considered due to leukemic organ involvement.
Note: Subjects with Gilbert's Syndrome may have a bilirubin > 1.5 × ULN per discussion between the investigator and AbbVie medical monitor.

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 23
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 68

Exclusion Criteria

1. Subject has received treatment with cytarabine for a pre-existing myeloid disorder.
2. Subject has acute promyelocytic leukemia .
3. Subject has known active CNS involvement with AML.
4. Subject has tested positive for HIV (due to potential drug-drug interactions between antiretroviral medications and venetoclax, as well as anticipated venetoclax mechanism-based lymphopenia that may potentially increase the risk of opportunistic infections). Note: HIV testing is not required.
5. Subject has received the following within 7 days prior to the initiation of study treatment:
? Strong and moderate CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort.
6. 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.
7. Subject has a cardiovascular disability status of New York Heart Association Class > 2. Class 2 is defined as cardiac disease in which subjects are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
8. Subject has a white blood cell count > 25 × 10 9/L. Note: Hydroxyurea is permitted to meet this criterion.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified