Acute Myelogenous Leukemia MedDRA version: 20.0 Level: LLT Classification code 10001941 Term: AML System Organ Class: 100000004864
Conditions
Interventions
Product Name: Venetoclax
Product Code: ABT-199 (GDC-0199)
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Venetoclax
Current Sponsor code: ABT-199 (GDC-0199)
Concentration unit: mg mill
Sponsors
AbbVie Deutschland GmbH & Co. KG
Eligibility
Sex/Gender
All
Inclusion criteria
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 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 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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: ? The primary objectives of the Phase 1 portion are to assess the safety profile, characterize pharmacokinetics (PK), determine the dose schedule, the maximum tolerated dose (MTD), and the recommended Phase 2 dose (RPTD) of venetoclax (ABT-199/GDC-0199) in combination with LDC in treatment-naïve subjects with AML who are = 65 years of age and who are not eligible for standard induction therapy due to co-morbidity or other factors. ? The primary objective of the initial Phase 2 portion of the study is to evaluate the leukemia response rate and duration and characterize the toxicities of the combination at the Recommended Phase 2 Dose (RPTD). ? The primary objective of Phase 2 Cohort C is to evaluate the ORR for subjects allowed additional supportive medications (strong CYP3A inhibitors) if medically indicated. ;Secondary Objective: The secondary objectives of the initial Phase 2 portion and Phase 2 Cohort C are to evaluate leukemia response (rates of CR, CRi, PR, and MLFS), duration of response (DOR) and overall survival (OS). ;Primary end point(s): ? Phase 1: Safety profile, characterize PK, maximum tolerated dose (MTD) and recommended phase 2 dose (RPTD) ? Phase 2: Overall response rate (ORR), Event Free Survival (EFS), and to characterize the toxicities of the combination at the RPTD. ;Timepoint(s) of evaluation of this end point: First week of treatment (MTD); throughout the study (Safety); Cycle 1 Day 1, Cycle 1 Day 10 and Cycle 1 Day 18 (PK); Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, every 12 Weeks thereafter and as clinically indicated and final visit (MRD and other phase 2 primary end points) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase 2: Response rates of CR, CRi, PR, RD, and HR, and Duration of Response (DOR) and overall survival (OS).;Timepoint(s) of evaluation of this end point: Cycle 1 Day 1, Cycle 2 Day 1, Cycle 4 Day 1, every 12 Weeks thereafter and as clinically indicated and final visit (MRD and other phase 2 primary end points) | — |
Countries
Australia, Germany, Italy, United States
Contacts
Public ContactEU Clinical Trials Helpdesk
AbbVie Ltd.
Outcome results
None listed