A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

Pfizer

Status and phase: Completed; Phase 2

Conditions: Acute Myeloid Leukemia

Treatments: Drug: Decitabine; Drug: Daunorubicin; Drug: PF-04449913; Drug: Cytarabine; Drug: Low dose ARA-C (LDAC)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01546038

2012-000684-24 (EudraCT Number)

B1371003

Details and patient eligibility

About

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.

Enrollment: 255 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients with AML or RAEB 2 High Risk MDS who are newly diagnosed according to the WHO 2008 Classification and previously untreated.
• Patients with AML (arising from an antecedent hematologic disease [AHD]) or MDS who may have had one prior regimen with commercially available agents for the treatment of their prior hematologic disease. The patients may not have had a prior therapy for their AML.
• AML patients include de novo AML, AML evolving from MDS or other AHD and AML after previous cytotoxic therapy or radiation (secondary AML)
• For a diagnosis of AML, a bone marrow blast count of 20% or more is required.
• For a diagnosis of high-risk Myelodysplastic Syndrome RAEB 2 the patient must have 10-19% bone marrow blasts
• Adequate Organ Function
• ECOG Performance Status 0, 1, or 2

Exclusion criteria

• AML M3 Acute Promyelocytic Leukemia (APL) or patients with a t(9:22) cytogenetic translocation.
• Patients with known active uncontrolled central nervous system (CNS) leukemia.

Trial design

255 participants in 5 patient groups

Arm A (Phase 1B)

Experimental group

Description:

PF-04449913 in combination with low dose ARA-C (LDAC)

Treatment:

Drug: PF-04449913

Drug: Low dose ARA-C (LDAC)

Drug: PF-04449913

Drug: PF-04449913

Drug: PF-04449913

Drug: Low dose ARA-C (LDAC)

Drug: PF-04449913

Arm B (Phase 1B)

Experimental group

Description:

PF-04449913 in combination with Decitabine

Treatment:

Drug: PF-04449913

Drug: PF-04449913

Drug: PF-04449913

Drug: PF-04449913

Drug: Decitabine

Drug: PF-04449913

Arm C (Phase 1B)

Experimental group

Description:

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.

Treatment:

Drug: PF-04449913

Drug: Daunorubicin

Drug: PF-04449913

Drug: Cytarabine

Drug: PF-04449913

Drug: Cytarabine

Drug: PF-04449913

Drug: PF-04449913

Drug: Daunorubicin

P2 Fit (Phase 2 Single Arm)

Experimental group

Description:

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.

Treatment:

Drug: PF-04449913

Drug: Daunorubicin

Drug: PF-04449913

Drug: Cytarabine

Drug: PF-04449913

Drug: Cytarabine

Drug: PF-04449913

Drug: PF-04449913

Drug: Daunorubicin

P2 Unfit (Phase 2 Randomized)

Other group

Description:

Patients will be randomized 2:1 (low dose ARA-C in combination with PF-04449913: low dose ARA-C alone).

Treatment:

Drug: PF-04449913

Drug: Low dose ARA-C (LDAC)

Drug: PF-04449913

Drug: PF-04449913

Drug: PF-04449913

Drug: Low dose ARA-C (LDAC)

Drug: PF-04449913