A Phase II Pilot Study of Glivec (imatinib mesylate formerly known as STI571) Combined with Induction Chemotherapy in Blast-Phase Chronic Myeloid Leukemia and Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia, to evaluate safety and improve remission rate.(CMLALL01)

Funding

Commercial sector/Industry,Novartis Australia

Scientific enquiries

Associate Professor Kenneth Bradstock

Brief Summary

Primary Objective: Investigation of the safety and tolerability of Glivec in combination with induction chemotherapy for blast-phase chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia Secondary Objective(s): (1) Investigation of the efficacy of Glivec combined with induction chemotherapy in Ph+ acute leukaemias (2) Biochemical evaluation of Abl kinase suppression by Glivec in leukaemic blasts Patients aged 16-70 with CML in blast crisis or Ph+ ALL All pati .... Primary Objective: Investigation of the safety and tolerability of Glivec in combination with induction chemotherapy for blast-phase chronic myeloid leukemia and Philadelphia chromosome-positive acute lymphoblastic leukemia Secondary Objective(s): (1) Investigation of the efficacy of Glivec combined with induction chemotherapy in Ph+ acute leukaemias (2) Biochemical evaluation of Abl kinase suppression by Glivec in leukaemic blasts Patients aged 16-70 with CML in blast crisis or Ph+ ALL All patients will receive Glivec 600 mg orally once daily, beginning 7 days prior to induction chemotherapy. Subsequent therapy will be delivered on one of three arms: (1) CML in myeloid blast crisis : Chemotherapy will consist of induction with idarubicin and standard-dose cytarabine, followed by consolidation with 2 cycles of intermediate-dose cytarabine. Glivec will be administered without interruption in combination with the chemotherapy and then continued as a single agent until relapse or unacceptable toxicity. (2) CML in lymphoid blast crisis and relapsed Ph+ ALL: Chemotherapy will consist of 8 courses of hyper-CVAD and Glivec will be administered as in Arm 1. (3) De-novo Ph+ ALL: Chemotherapy will be given according to the French cooperative group ALL protocol (LALA 94). Glivec will be continued synchronously with induction, consolidation and maintenance chemotherapy, except for an interruption during cranial radiation.
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Key Inclusion Criteria

1. Patients with a confirmed diagnosis of Ph+ CML in myeloid or lymphoid blast crisis, defined by the presence of the Philadelphia chromosome or Bcr-Abl fusion transcript and one or both of the following: i) >30% blasts in peripheral blood and/or bone marrow ii) Presence of extramedullary disease other than spleen and/or liver involvement (i.e. chloromas) OR Patients with a confirmed diagnosis of Ph+ ALL 2. Patients of childbearing potential must have a negative pregnancy test prior to the initi .... 1. Patients with a confirmed diagnosis of Ph+ CML in myeloid or lymphoid blast crisis, defined by the presence of the Philadelphia chromosome or Bcr-Abl fusion transcript and one or both of the following: i) >30% blasts in peripheral blood and/or bone marrow ii) Presence of extramedullary disease other than spleen and/or liver involvement (i.e. chloromas) OR Patients with a confirmed diagnosis of Ph+ ALL 2. Patients of childbearing potential must have a negative pregnancy test prior to the initiation of therapy. Male and female patients agree to employ an effective barrier method of birth control throughout the study and for up to 3 months following the discontinuation of Glivec. 3. Written informed consent.
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Key Exclusion Criteria

1. Exposure to any other investigational agents within 30 days of commencing Glivec 2. Known sensitivity to Glivec or the phenylaminopyrimidine class of drugs 3. ECOG Performance Status Score > 2 (Appendix 1) 4. Left ventricular ejection fraction < 50% on a radionuclide cardiac scan or echocardiogram 5. Creatinine > 1.5 ´ the upper limit of normal (ULN) at the laboratory where the analysis was performed 6. Serum bilirubin > 2 ´ ULN 7. AST or ALT > 2.5 ´ ULN. In patients with suspected leukaem .... 1. Exposure to any other investigational agents within 30 days of commencing Glivec 2. Known sensitivity to Glivec or the phenylaminopyrimidine class of drugs 3. ECOG Performance Status Score > 2 (Appendix 1) 4. Left ventricular ejection fraction < 50% on a radionuclide cardiac scan or echocardiogram 5. Creatinine > 1.5 ´ the upper limit of normal (ULN) at the laboratory where the analysis was performed 6. Serum bilirubin > 2 ´ ULN 7. AST or ALT > 2.5 ´ ULN. In patients with suspected leukaemic involvement of the liver, AST or ALT > 5 ´ ULN. 8. Known HIV seropositivity 9. Any serious concomitant medical condition that could, in the opinion of the Investigator, compromise participation in the study 10. Pregnancy or breastfeeding 11. Dementia, intellectual impairment or any other psychiatric disorder that prohibits the patient from understanding and giving informed consent.
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