A Phase II study of midostaurin in combination with standard chemotherapy in newly diagnosed patients with Core Binding Factor Acute Myeloid Leukaemia
- Conditions
- Core binding factor (CBF) Acute myeloid leukaemia (AML)Cancer - Leukaemia - Acute leukaemia
- Registration Number
- ACTRN12612000847819
- Lead Sponsor
- Australasian Leukaemia and Lymphoma Group
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Withdrawn
- Sex
- All
- Target Recruitment
- 50
1.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
2.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).
3.Age between 15 and 65 inclusive
4.Life expectancy at least 3 months
5.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
6.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
7.An Eastern Cooperative Oncology Group (ECOG) performance status score of 2 or less
8.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).
9.Has provided written informed consent
1.Prior therapy for AML (Hydroxyurea allowed up to 5 days and circumstances in Inclusion criterion 8 will be considered)
2.Patients with central nervous sytem (CNS) involvement with AML
3.Serious cardiac or pulmonary dysfunction precluding the delivery of the proposed therapy
4.Women who are pregnant or lactating. Women of child-bearing potential must have a negative serum pregnancy test at Screening.
5.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
6.Contraindication to the use of study drugs
7.Severe active infection
8.Known human immunodeficiency virus (HIV) or Hepatitis C Virus (HCV) infection or Hepatitis V virus surface antigen (HBV-sAg) positivity
9.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
10.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.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method