AMLM26/T2 INTERCEPT: A multi-arm trial for patients with acute myeloid leukaemia investigating new treatments which target early relapse and changes in disease characteristics - Ivosidenib + Venetoclax

Phase 1

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

• Registration Number: ACTRN12624000141549
• Lead Sponsor: Australasian Leukaemia & Lymphoma Group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-02-15
• Last Update Posted: 3 June 2024

Recruitment & Eligibility

• Status: ot yet recruiting
• Sex: All
• Target Recruitment: 69

Inclusion Criteria

1. Meets inclusion criteria outlined in the AMLM26 INTERCEPT Master Protocol(see ACTRN12621000439842 for details on the master protocol).
2. Presence of an IDH1 mutation in a bone marrow or peripheral blood sample taken no more than 28 days prior to cycle 1 day 1 of treatment on this treatment arm
3. ECOG 0-2
4. 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
5. Subject must have adequate liver function as demonstrated by:
a. aspartate aminotransferase (AST) less than or equal to 3.0 × ULN
b. alanine aminotransferase (ALT) less than or equal to 3.0 × ULN
c. bilirubin less than or equal to 1.5 × ULN (unless bilirubin rise is due to Gilbert’s syndrome or of non-hepatic origin)
6. Agrees to follow the recommended contraception procedures for this treatment domain

Exclusion Criteria

1. Presence of any general exclusion criteria outlined in the AMLM26 INTERCEPT Master Protocol (see ACTRN12621000439842 for details on the master protocol)
2. QT-interval corrected according to Fridericia’s formula (QTcF) greater than 450ms (except for right bundle branch block)
3. Prior allogeneic stem cell transplant within 30 days of post-transplant conditioning, or on immunosuppression for graft vs host disease (GVHD) (other than less than or equal to 10mg/day of prednisolone which is permitted).
4. Subject is HIV positive
5. 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) or patients who have past exposure to HepB (HepB Surface Antigen negative but core antibody positive and DNA negative) who do not require treatment may participate.
6. Treatment with any of the following within 7 days prior to the first dose of study drug:
a. Steroid therapy for anti-neoplastic intent, or greater than 10mg/day prednisolone for graft versus host disease
b. Moderate or strong CYP3A inducers
c. Moderate or strong cytochrome CYP3A inhibitors are prohibited 7 days prior to cycle 1 day 1. They are prohibited during cycle 1 of the pilot safety run-in phase and during venetoclax dose ramp-up in all phases. At other times they may be used if required with caution and with appropriate dose modifications for venetoclax
7. 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
8. Treatment with prior anti-leukemic therapy within 14 days prior to the first dose of study drug. (except steroids see exclusion 5a)
9. Subject has been diagnosed with another malignancy, unless disease-free for at least 2 years and not needing active treatment. Patients with fully excised BCC/SCC/CIN or other minor malignancy are not excluded.
10. Subject has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation
11. Subject has radiation therapy within 4 weeks prior to the first study dose.
12. Subject has congestive heart failure New York Heart Association (NYHA) class 3 or 4 or subject with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram or gated cardiac blood pool scan performed within 1 month prior to study entry results in a left ventricular ejection fraction that is greater than or equal to 45%.

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
To determine the response of patients with IDH1 mutated AML in the MRD failure stratum to their first-exposure to decision rule guided therapy with venetoclax and ivosidenib[To do this blood and bone marrow samples will be collected to assess your disease levels. The primary endpoint is MRD response within 100 days of Cycle 1 Day 1. MRD response is defined as a reduction of greater than or equal to 1-log in the molecular marker, and/or MRD negativity, or less than 0.1% aberrant disease by flow cytometry]