A Combination Study of PF-04449913 (Glasdegib) and Azacitidine In Untreated MDS, AML and CMML Patients (BRIGHT 1012)

Pfizer

Status and phase: Completed; Phase 1

Conditions: Myelodysplastic Syndrome; Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia

Treatments: Drug: PF-04449913 (Glasdegib); Drug: Azacitidine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02367456

2014-001345-24 (EudraCT Number)

BRIGHT MDS&AML1012 (Other Identifier)

B1371012

Details and patient eligibility

About

This multi center open label Phase 1b study is designed to evaluate the safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) of glasdegib (PF-04449913) when combined with azacitidine in patients with previously untreated Higher Risk Myelodysplastic Syndrome (MDS), Acute Myeloid Leukemia (AML), or Chronic Myelomonocytic Leukemia (CMML). This clinical study includes two components: (a) a safety lead in cohort (LIC) and (b) an expansion phase with an AML cohort and an MDS cohort.

Enrollment: 73 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients must have previously untreated MDS, AML, or CMML according to the WHO 2016 classification.
• MDS patients must have Intermediate (>3 to 4.5 points), High Risk (>4.5 - 6) or Very High Risk (>6 points) disease according to the Revised International Prognostic Scoring System 2012 (IPSS-R).
• Clinical indication for treatment with azacitidine for MDS or AML.

Exclusion criteria

• Patients with AML who are candidates for standard induction chemotherapy as first line treatment.
• Patients with known active CNS leukemia.
• Prior treatment with a smoothened inhibitor (SMOi) and/or hypomethylating agent.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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73 participants in 2 patient groups

Arm A

Experimental group

Description:

MDS patients: PF-04449913 (Glasdegib) 100 mg + Azacitidine 75 mg/m2

Treatment:

Drug: Azacitidine

Drug: PF-04449913 (Glasdegib)

Arm B

Experimental group

Description:

AML patients: PF-04449913 (Glasdegib) 100 mg + Azacitidine 75 mg/m2

Treatment:

Drug: Azacitidine

Drug: PF-04449913 (Glasdegib)