Optimising therapy in FLT3-mutated acute myeloid leukaemia

Phase 2

• Conditions: Acute myeloid leukemia; Cancer

• Registration Number: ISRCTN34016918
• Lead Sponsor: Cardiff University

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2024-07-30
• Last Update Posted: 12 August 2024
• Study Completion: 2030-12-31

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 390

Inclusion Criteria

1. Diagnosis of AML
2. Age =16 years (no specified upper age limit)
3. Considered fit for intensive AML therapy by the treating physician
4. Confirmed FLT3 ITD or TKD mutation (or FLT3 status unknown but requires urgent therapy - see below*)
5. Serum creatinine less than or equal to 1.5 x ULN (upper limit of normal)
6. Serum Alanine Aminotransferase (ALT) and Aspartate Aminotransferase (AST) less than or equal to 2.5 x ULN and bilirubin less than or equal to 2 x ULN
7. A negative pregnancy test within 2 weeks prior to trial entry in WOCBP (to be repeated throughout the trial prior to each course of protocol treatment)
8. Sexually mature males and females must agree to use an adequate and medically accepted method of contraception throughout the study and for 6 months following treatment if they or their sexual partners are women of childbearing potential (WOCBP)
9. WHO performance status 0-2
10. Written informed consent

*FLT3-mutated AML is associated with proliferative disease features such as hyperleukocytosis (high white blood cell count) and may present as a medical emergency. It is important that the full clinical spectrum of FLT3-mutated AML is represented in Optimise-FLT3, including hyper-proliferative cases. Should the treating physician feel that the safety of an individual patient could be compromised by delaying therapy while awaiting FLT3 genotyping, they may, on discussion with the study team, proceed with study entry (using PIS2), randomisation and treatment provided all other eligibility criteria are met. Any patients who enter the trial and are subsequently found to have wild-type FLT3 will be considered evaluable for safety/toxicity analysis but will be replaced with additional FLT3-mutated cases to maintain statistical power for the clinical efficacy endpoints and equipoise between arms.

Exclusion Criteria

1. Receipt of any previous therapy for AML or any antecedent haematological condition (the use of oral hydroxycarbamide to control white blood cell count is permitted)
2. Other active malignancy requiring treatment
3. Patients who are pregnant or lactating
4. Uncontrolled infection with Human Immunodeficiency Virus (HIV) or Hepatitis B or C. Patients with known chronic infections who are receiving or have completed therapy and have recent documented negative viral PCR tests are not excluded
5. Blast transformation of chronic myeloid leukaemia (CML)

Study & Design

• Study Type: Interventional
• Study Design: Not specified