A phase Ib clinical evaluation of Venetoclax in combination with chemotherapy in older patients with Acute Myeloid Leukemia

Phase 1

Recruiting

• Conditions: Acute myeloid leukaemia; Cancer - Leukaemia - Acute leukaemia

• Registration Number: ACTRN12616000445471
• Lead Sponsor: Alfred Health

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-04-06
• Last Update Posted: 13 January 2020

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: 48

Inclusion Criteria

1. De novo, secondary or therapy-related AML (except Acute Promyelocytic Leukaemia) without prior exposure to induction chemotherapy (not including hydroxyurea, low-dose cytarabine eg ~20mg bd, hypomethylating agents or non-chemotherapy-based investigational agents)
2. Age greater than or equal to 65
3. Or Age greater than or equal to 60 and monosomal karyotype
4. ECOG performance status 0-1
5. Adequate hepatic function as defined by bilirubin less than or equal to 1.5 x the upper limit of normal (ULN, excluding Gilbert’s syndrome) and AST & ALT less than or equal to 2.5 x ULN (unless due to leukemic involvement)
6. Adequate renal function as defined by eGFR>50ml/min as assessed by eCCr =(140 – Age) x (Weight in kg) x [1.23 if Male, 1.04 if Female]/Serum Creatinine (micromol/L)
7. WCC less than 25 x 109/L (hydroxyurea allowable to reduce WCC prior to day 1 of study)

Exclusion Criteria

1. Prior investigational anti-leukemia agents within 14 days of day 1 of study drug; demethylating agents within 14 days of day 1 of study drug; and hydroxyurea within 24 hrs prior to day 1 of study drug.
2. Prior exposure to Venetoclax or other BCL2 inhibitors
3. Prior anthracycline exposure for previous cancer
4. Any serious medical condition which the investigator feels may lead to an unacceptably high risk of treatment related death from 5+2 induction
5. Concurrent malignancy likely to affect treatment safety or study procedures
6. Known HIV infection
7. Uncontrolled viral hepatitis type B or C
8. Males with a female partner of childbearing potential must agree to use at least 2 effective contraceptive methods throughout the study and for 30 days following the date of last dose
9. Cardiac ejection fraction <45%
10. Subject has received the following within 7 days prior to the initiation of study treatment:
*Potent CYP3A inducers such as rifampin, carbamazepine, phenytoin, and St. John's wort;
*Warfarin or requires the use of warfarin (due to potential drug-drug interactions that may potentially increase the exposure of warfarin and complications of this effect).
11. Subject has received the following within 5 days prior to the initiation of study treatment:
* CYP3A inhibitors such as fluconazole, ketoconazole, and clarithromycin.
12. 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.
13. Subject has a history of other malignancies prior to study entry, with the exception of:
*Adequately treated in situ carcinoma of the breast or cervix uteri;
*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.
*Prior malignancy treated >4 years ago and no evidence of active disease

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To assess the safety of Venetoclax in combination with idarubicin and cytarabine in frontline AML therapy through analysis of dose limiting toxicity during induction in each cohort. Fever, low red blood cell count, low white blood cell count, low platelet count, fever, tumor lysis syndrome and other adverse reactions/events to be assessed through review of peripheral blood examinations and other medical records.[Analysis during induction cycle]