High-dose lenalidomide maintenance therapy in adult acute myeloid leukaemia (AML)
A pilot study exploring high-dose lenalidomide maintenance therapy in adult acute myeloid leukaemia (AML)
Australasian Leukaemia and Lymphoma Group (ALLG)
50 participants
Aug 23, 2011
Interventional
Conditions
Summary
Lenalidomide has a variety of reported mechanisms in blood malignancy, including activation of immune cells and anti-proliferative effects on tumor cells and modulation of the bone marrow microenvironment. Currently approved doses of lenalidomide use up to 25 mg for 21 days out of 28. A recent pilot study in older AML patients used higher and continuous doses of lenalidomide (50mg lenalidomide for 28 days x 2 cycles followed by 10 mg daily for 12 months). This resulted in a 30% complete response rate. This schedule was well tolerated in an elderly AML population. Therefore, lenalidomide at higher doses has substantial activity in AML and deserves further exploration. To explore the potential clinical value of lenalidomide in prolonging remission in adult AML after chemotherapy, this multicentre Investigator Initiated Australasian study will first investigate the safety and tolerability of increasing doses of lenalidomide (10-50mg per day for 28 days for 2 months) followed by 10mg per day for 10 months.
Eligibility
Inclusion Criteria2
- Subjects aged 15 - 65 years at screening. Newly diagnosed acute myeloid leukaemia (except APML) with morphology according to the World Health Organisation (WHO) criteria and confirmed by immunophenotyping. This can include de-novo and secondary/therapy related AML. The inclusion of patients with core binding factor AML and the presence of Fms-like tyrosine kinase 3 (FLT3) mutations will be allowable if patients are not enrolled for other studies targeting these disease groups. Has provided written, informed consent. Life expectancy greater than 3 months. Has registered prior to induction therapy and provided samples at registration for tissue bank and
- laboratory studies and during induction and consolidation therapy for correlative studies. Subjects should have completed recommended induction and consolidation therapy as outlined in protocol. If subjects have had dose modifications, eligibility should be discussed with the Principal Investigator. Patients must have achieved complete remission (CR), complete remission with incomplete platelet recovery (CRp) or complete remission with incomplete count recovery (CRi) after one or two rounds of induction chemotherapy before progressing to consolidation chemotherapy. Patients must be in CR or CRp after consolidation chemotherapy. Lenalidomide therapy must be able to commence within 6-16 weeks since completion of the last dose of consolidation chemotherapy. No clinical evidence of deep vein thrombosis. An Eastern Co-operative Oncology Group (ECOG) performance status score of 2 or less at screening. Adequate baseline bone marrow reserve (neutrophils >1.0 x 10^9/L and platelets >75 x 10^9/L) immediately prior to treatment. Adequate cardiac function. Adequate renal and hepatic functions at screening as defined by:a. bilirubin less than or equal to 2 x upper limit of normal (ULN) b. serum creatinine less than or equal to 1.5 x ULN c. Alanine aminotransferase (ALT) less than or equal to 3 x ULN. Ability to comply with the contraceptive and other requirements of the Lenalidomide Risk Management Plan. Subjects must agree not to share their medication and return unused supplies
Exclusion Criteria3
- History of major non-compliance to medication. Evidence of known central nervous system (CNS) leukaemia. Currently active gastrointestinal disease (e.g., ulcerative diseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or small bowel resection), or other disease, that, in the nvestigator’s
- opinion, prevents the patient from absorbing or taking oral medication. Any other concurrent severe and/or uncontrolled medical conditions (eg. acute or chronic liver disease, infection, pulmonary disease) or clinical abnormalities that in the opinion of the investigator could
- potentiate unacceptable safety risks or jeopardise compliance with the protocol. Significant cardiac or respiratory disease. Prior diagnosis of cancer that was either: a. more than 5 years prior to current diagnosis with subsequent evidence of disease recurrence or clinical expectation of recurrence is greater than 10% OR b. within 5 years of current diagnosis with the exception of successfully treated basal cell or squamous cell skin carcinoma or carcinoma in situ of the cervix. Previous adverse reaction to the trial drug/s. Women who are pregnant or lactating. Planned Haemopoietic stem cell transplant (HSCT) within 3 months of commencing maintenance lenalidomide. Delay between day 28 of final induction cycle and day 1 of first cycle of consolidation therapy was greater than 8 weeks. Granulocyte colony stimulating factor (GCSF) within 7 days of commencing lenalidomide treatment. Uncontrolled viral infection with Human Immunodeficiency Virus (HIV) or Hepatitis type B or C.
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Interventions
Daily oral lenalidomide maintenance therapy for consecutive 28 day cycles. The first two cycles will be 'high dose' lenalidomide (10-50mg depending on which of 5 cohorts is currently accruing patients), and then patients will complete up to 10 additional 28 day cycles of 10mg oral lenalidomide daily. Cohort 1: 10mg daily for first two cycles; then if approved by Trial Management Committee (TMC) Cohort 2: 25mg daily for first two cycles; then if approved by TMC Cohort 3: 30mg daily for first two cycles; then if approved by TMC Cohort 4: 40mg daily for first two cycles; then if approved by TMC Cohort 5: 50mg daily for first two cycles
Locations(1)
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ACTRN12610000627055