A Study Evaluating Intensive Chemotherapy With or Without Glasdegib or Azacitidine With or Without Glasdegib In Patients With Previously Untreated Acute Myeloid Leukemia

Official Title

A randomized (1:1), double-blind, multi-centre, placebo controlled study evaluating intensive chemotherapy with or without glasdegib (pf-04449913) or azacitidine (aza) with or without glasdegib in patients with previously untreated acute myeloid leukemia

Summary:

Glasdegib is being studied in combination with azacitidine for the treatment of adult patients with previously untreated acute myeloid leukemia (AML) who are not candidates for intensive induction chemotherapy (Non-intensive AML population). Glasdegib is being studied in combination with cytarabine and daunorubicin for the treatment of adult patients with previously untreated acute myeloid leukemia (Intensive AML population).

Trial Description

Primary Outcome:

• Overall survival

Secondary Outcome:

• Fatigue score measured by the MD Anderson Symptom Inventory (MDASI)-AML/MDS questionnaire
• Rate of Complete Remission (CR) (including CR with minimal residual disease (MRD)-negative as assessed by multiparametric flow cytometry)
• Duration of response (defined as CR [includes CR-MRD negative]/CRi or CR/CRh as appropriate)
• Time to response (CR[includes CR-MRD negative)]/CR with partial hematologic rcovery (CRh) as appropriate)
• Event-free Survival
• Patient Reported Outcomes (PROs) as measured by the M.D. Anderson Symptom Inventory AML/MDS Module (MDASI-AML/MDS)
• Adverse events as graded by NCI CTCAE v4.03
• Laboratory abnormalities as graded by NCI CTCAE v4.03
• For the intensive study, the plasma trough concentration (Ctrough) will be analyzed
• QTc interval
• PROs as measured by Patient Global Impression of Change (PGIC)
• Patient Reported Outcomes (PROs) as measured by EuroQoL 5 Dimension questionnaire 5-Level version (EQ-5D-5L)
• Patient Reported Outcomes (PROs) as measured by Patient Global Impression of Symptoms (PGIS)
• Complete Remission with incomplete hematologic recovery (CRi)
• Rate of morphological leukemia-free state (MLFS)
• Rate of Partial Remission (PR)
• Rate of Complete Remission with partial hematological recovery (CRh) for the Non-intensive study only only
• Minimum Observed Plasma Trough Concentratrion of glasdegib in the Intensive Study
• Minimum Observed Plasma Trough Concentration of glasdegib in the Non-intensive study

Two separate registration trials conducted under one protocol number are proposed to adequately and independently evaluate the addition of glasdegib in intensive and non-intensive chemotherapy populations. Each study will have an experimental treatment arm and a placebo arm. Endpoints are the same for each study except where specifically indicated. Assignment to the Intensive Study or the Non-Intensive Study will be made by the Investigator based on the 2017 European LeukemiaNet (ELN) recommendations. Study B1371019 is a randomized (1:1), double-blind, multi-centre, placebo controlled study of chemotherapy in combination with glasdegib versus chemotherapy in combination with placebo in adult patients with previously untreated AML. Glasdegib is being studied in combination with azacitidine for the treatment of adult patients with previously untreated acute myeloid leukemia (AML) who are not candidates for intensive induction chemotherapy (Non-intensive AML population). Glasdegib is being studied in combination with cytarabine and daunorubicin for the treatment of adult patients with previously untreated acute myeloid leukemia (Intensive AML population).

View this trial on ClinicalTrials.gov