Conditions: Acute Myeloid Leukemia
Keywords: Hedgehog Inhibitor Acute Myeloid Leukemia Myelodysplastic syndrome Intensive chemotherapy LDAC glasdegib
Allocation: RANDOMIZED | Intervention model: 
Enrollment: 255
Healthy volunteers: no

Brief summary:
This is a study to evaluate PF-04449913 (an inhibitor of the Hedgehog pathway) in Acute Myeloid Leukemia and high-risk Myelodysplastic Syndrome in combination with standard agents used to treat these diseases.

Detailed description:

Arms:
arm 1: PF-04449913 in combination with low dose ARA-C (LDAC) arm 2: PF-04449913 in combination with Decitabine arm 3: PF-04449913 in combination with intensive chemotherapy: PF-04449913 administered continuously for 28 days. Daunorubicin given using 60 mg/m2 for 3-days together with cytarabine 100 mg/m2 on days 1 through 7 followed by cytarabine 1g/m2 on days 1, 3, and 5 during 2-4 cycles of consolidation therapy. arm 4: PF-04449913 in combination with intensive chemotherapy: PF-04449913 administered continuously for 28 days. Daunorubicin given using 60 mg/m2 for 3-days together with cytarabine 100 mg/m2 on days 1 through 7 followed by cytarabine 1g/m2 on days 1, 3, and 5 during 2-4 cycles of consolidation therapy. arm 5: Patients will be randomized 2:1 (low dose ARA-C in combination with PF-04449913: low dose ARA-C alone).

Interventions: intervention 1: PF-04449913 intervention 2: Low dose ARA-C (LDAC) intervention 3: PF-04449913 intervention 4: Decitabine intervention 5: PF-04449913 intervention 6: Daunorubicin intervention 7: Cytarabine intervention 8: PF-04449913 intervention 9: Daunorubicin intervention 10: Cytarabine intervention 11: PF-04449913 intervention 12: Low dose ARA-C (LDAC)
Intervention descriptions: intervention 1: PF-04449913 administered orally and continuously for 28-days. intervention 2: Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10. intervention 3: PF-04449913 administered orally and continuously for 28 days. intervention 4: Decitabine given at 20 mg/m2 over 1 hour infusion for 5-days intervention 5: PF-04449913 administered orally and continuously for 28 days intervention 6: Daunorubicin given using 60 mg/m2 for 3-days intervention 7: Cytarabine 100 mg/m2 on days 1 through 7 intervention 8: PF-04449913 administered orally and continuously for 28 days intervention 9: Daunorubicin given using 60 mg/m2 for 3-days intervention 10: Cytarabine 100 mg/m2 on days 1 through 7 intervention 11: PF-04449913 administered orally and continuously for 28 days (if randomized to receive PF-04449913) intervention 12: Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.

Protocol document: