RecruitingPhase 2ACTRN12619000280101

AMLM22/D2-The International Acute myeloid leukaemia (AML) Platform Consortium (IAPC) trial is a randomised, multi-arm study platform to compare the efficacy of experimental therapies versus standard of care in subjects with acute myeloid leukaemia in first complete remission. Domain 2 is investigating the safety and efficacy of Venetoclax as a maintenance therapy alone or in combination with low dose cytarabine (LDAC).

Sponsor

Australian Leukaemia and Lymphoma Group (ALLG)

Enrollment

75 participants

Start Date

Jul 8, 2020

Study Type

Interventional

Conditions

Acute Myeloid Leukaemia (AML)

Summary

This study will evaluate the safety and efficacy of venetoclax alone or in combination with low-dose cytarabine (LDAC) for Acute Myeloid Leukemia Who is it for? You may be eligible to join this study if you are aged 16 and above and have Acute Myeloid Leukemia in first complete remission. Study details This study is part of the International AML Platform Consortium. Participants in this study will be randomly allocated (by chance) to one of three treatment groups. Participants in one group will receive standard care which is generally observation. Participants in the other groups will receive the drug Venetoclax daily for a total of 24 months or Venetoclax in combination with low-dose cytarabine (LDAC) for a total of 24 months. As part of the study, participants will have blood tests at the start of each cycle (every 28 days) as well as additional blood tests depending on the treatment arm you have been randomised to. These additional blood tests are to monitor the level of neutrophils (type of white blood cell that is important in fighting infection) and platelets (platelets help your blood clot) We hope that the results from this trial will be used to help these new treatments which may be better for people with AML than what is currently available become accessible to the general population at faster than the normal process.

Eligibility

Sex: Both males and femalesMin Age: 16 Yearss

Inclusion Criteria12

Provision of written informed consent
Provision of written informed consent to the ALLG NBCR
Age 18+ (Age 16-17 permitted if consent for minor PICF approved by the authorizing HREC)
AML (excluding APL) in first complete remission with bone marrow blasts <5%
Subject has achieved remission after intensive chemotherapy (e.g. 7+3 or equivalent +/- subsequent consolidation therapy)
ECOG 0-2
Subject must have adequate renal function as demonstrated by a creatinine clearance greater than or equal to 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24-hours urine collection
Subject must have adequate liver function as demonstrated by:
a. aspartate aminotransferase (AST) greater than or equal to 3.0 × ULN
b. alanine aminotransferase (ALT) greater than or equal to 3.0 × ULN
c. bilirubin greater than or equal to 1.5 × ULN (unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin)
Agrees to follow the recommended contraception procedures for this treatment domain

Exclusion Criteria22

Chemotherapy or investigational agents within 28 days of planned study cycle 1 day
Impaired hematologic recovery 8 weeks after last chemotherapy
a. Grade 2 anemia (Hb <100g/L)
b. Grade 4 neutropenia (N <0.5 x 109/L)
c. Grade 3 thrombocyotopenia (Plt <50 x 109/L)
History of other malignancy requiring active systemic treatment or which is likely to result in an expected survival time of < 2 years
Viral infection with known HIV or viral hepatitis type B or C not adequately controlled by antiviral medication
Prior bone marrow or stem cell transplantation
There is an intent to undertake a stem cell transplant procedure within the next 3 months
Subject is HIV positive
Evidence of other clinically significant uncontrolled condition(s) including, but not limited to:
a. Uncontrolled and/or active systemic infection (viral, bacterial or fungal)
b. Chronic hepatitis B virus (HBV) or hepatitis C (HCV) requiring treatment. Note: subjects with serologic evidence of prior vaccination to HBV (i.e. hepatitis B surface (HBs) antigen negative-, anti-HBs antibody positive and anti-hepatitis B core (HBc) antibody negative) or positive anti-HBc antibody from intravenous immunoglobulins (IVIG) may participate.
Treatment with any of the following within 7 days prior to the first dose of study drug:
a. Steroid therapy for anti-neoplastic intent
b. Moderate or strong CYP3A inducers
c. Moderate or strong cytochrome CYP3A inhibitors may be used with caution with appropriate dose modifications for venetoclax
Administration or consumption of any of the following within 3 days prior to the first dose of study drug:
a. Grapefruit or grapefruit products
b. Seville oranges (including marmalade containing Seville oranges)
c. Star fruit
Subject not able to comply with domain-specific contraception recommendations

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Interventions

Domain 2 is AMLM22/D2, it has 3 treatment arms: Arm 1: Venetoclax (investigational product) plus Low-dose cytarabine (LDAC). Recommended dose of Venetoclax is 600mg daily, taken orally on days 1-28 o

Domain 2 is AMLM22/D2, it has 3 treatment arms: Arm 1: Venetoclax (investigational product) plus Low-dose cytarabine (LDAC). Recommended dose of Venetoclax is 600mg daily, taken orally on days 1-28 of each cycle. Low dose cytarabine (LDAC) is given subcutaneously (under the skin) at a dose of 20mg/m2 daily on days 1-10 of each 28-day cycle, following administration of venetoclax. Each cycle is 28 days. Total treatment duration is expected to be 24 months. Arm 2: Venetoclax monotherapy. Recommended dose of Venetoclax is 800mg daily, taken orally on days 1-28 of each cycle. Each cycle is 28 days. Total treatment duration is expected to be 24 months. Arm 3: Standard of care (generally observation) Patients randomised to receive venetoclax will be asked to return any unused tablets at each visit.