A Phase II study of midostaurin in combination with standard chemotherapy in newly diagnosed patients with Core Binding Factor Acute Myeloid Leukaemia
A Phase II study of failure-free survival following treatment with midostaurin in combination with standard chemotherapy in newly diagnosed patients with Core Binding Factor Acute Myeloid Leukaemia
Australasian Leukaemia and Lymphoma Group
50 participants
Mar 1, 2013
Interventional
Conditions
Summary
This study aims to determine the safety and efficacy of treatment with the drug midostaurin, in combination with intensive chemotherapy for adults with previously untreated core binding factor (CBF) acute myeloid leukaemia (AML). Who is it for? You may be eligible to join this study if you are aged between 15-65 years and have been diagnosed with AML with CBF subtype. You must have received no previous treatment for AML. Trial details All participants in this trial will undergo intensive chemotherapy over a period of 18 months, that will include the addition of midostaurin twice a day during some of that time. Midostaurin is a new chemotherapy drug thought to be particularly effective in CBF AML. Participants will then be assessed at regular timepoints for between 1 to 5 years to determine the safety and clinical benefit of midostaurin treatment in combination with chemotherapy. This Phase II study will: Investigate the clinical benefit, safety and potential extended survival following therapy with frontline midostaurin in combination with chemotherapy and during maintenance therapy in adult AML
Eligibility
Inclusion Criteria13
- Newly diagnosed patients with a morphologically confirmed diagnosis of AML with t(8;21); RUNX1-RUNX1T1 or AML with inv(16) or t(16;16); CBFB-MYH11 by World Health Organisation criteria which includes patients with <20% blasts in the presence of cytogenetic or molecular evidence of a CBF subtype
- Confirmation of CBF subtype by cytogenetic finding (including Fluorescence in situ hybridization (FISH)) of t(8;21)(q22;q22) or inv(16)(p13;q22) or t(16;16)(p13;q22) (either alone or in combination with other cytogenetic abnormalities) OR polymerase chain reaction (PCR) evidence of a CBF fusion transcript (RUNX1-RUNX1T1 or CBF-MYH11).
- Age between 15 and 65 inclusive
- Life expectancy at least 3 months
- Females of childbearing potential use a highly effective method of contraception and a form of barrier contraception for the duration of the study and for 3 months after midostaurin treatment is ceased
- Adequate renal and hepatic functions to enable safe delivery of chemotherapy.
- a.Total bilirubin <1.5 x Upper Limit of Normal (ULN)
- b.aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) <2.5 ULN
- c.serum creatinine <250micromol/L
- Patients not meeting these criteria should be discussed with Principal Investigator
- An Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less
- Patients must be registered prior to the commencement of induction therapy. Where there is a need for urgent commencement of induction therapy, patients with subsequent confirmation of the CBF subtype following commencement of induction therapy may be considered, after discussion with a study Principal Investigator, for inclusion in this trial. The continuation, or modification, of the induction phases of their treatment will be determined by the investigator in consultation with a Principal Investigator, but post-remission consolidation therapy will follow the treatment plan for this study (AMLM19).
- Has provided written informed consent
Exclusion Criteria12
- Prior therapy for AML (Hydroxyurea allowed up to 5 days and circumstances in Inclusion criterion 8 will be considered)
- Patients with central nervous sytem (CNS) involvement with AML
- Serious cardiac or pulmonary dysfunction precluding the delivery of the proposed therapy
- Women who are pregnant or lactating. Women of child-bearing potential must have a negative serum pregnancy test at Screening.
- Prior diagnosis of cancer that was:
- a.more than 5 years prior to current diagnosis with subsequent evidence of disease recurrence or clinical expectation of recurrence is greater than 10%
- 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
- Contraindication to the use of study drugs
- Severe active infection
- Known human immunodeficiency virus (HIV) or Hepatitis C Virus (HCV) infection or Hepatitis V virus surface antigen (HBV-sAg) positivity
- Has any other clinically important abnormalities as determined by the investigator that may interfere with his or her participation in or compliance with the study
- Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule. This condition must be discussed with the patient prior to signing consent and registration in the trial.
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Interventions
Patients will receive stages of treatment outlined in sections 1,2 and 3 sequentially. 1. 1 28 day cycle of induction chemotherapy consisting of idarubicin (IV 12mg/m^2 days 1-3), cytarabine(IV 100mg/m^2 days 1-7) and with twice daily oral 50mg midostaurin on days 8-21 of each cycle. Patients who do not achieve complete remission can undergo another cycle of induction therapy 2. Up to 4x28 day cycles, depending on tolerability, of high dose cytarabine (Ara-C) (3g/m^2 IV every 12 hours on days 1,3,5) with twice daily oral 50mg midostaurin on days 8-21 of each cycle. Consolidation chemotherapy should begin once patient has attained complete remission, including neutrophils of at least 1.0 x 10^9/L and platelets of at least 100 x 10^9/L. 3. Maintenance chemotherapy consisting of twice daily oral 50mg midostaurin on days 1-28 of each 28 day cycle for 12 consecutive cycles. Maintenance therapy should be commenced after haematologic recovery between days 36 and 64 from the commencement of the last consolidation cycle
Locations(1)
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ACTRN12612000847819