GLAD-AML - Glasdegib (Pf-04449913) With Two Standard Decitabine Regimens for Older Patients With Poor-risk Acute Myeloid Leukemia

NCT04051996 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 2000024738
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

This multi-center, randomized phase 2 study is designed to evaluate the complete remission (including complete remission with incomplete count recovery) rates of glasdegib in combination with either decitabine on a 5-day or 10-day schedule in patients with newly-diagnosed poor-risk AML who either refuse or are ineligible for intensive therapy.

Conditions

ACUTE MYELOID LEUKEMIA

Outcome Measures

Primary Outcomes (1)

• CR/CRi

  The complete remission (CR) and complete remission with incomplete count recovery (CRi) combined rate will be defined by the 2017 European LeukemiaNet (ELN) AML response criteria.

  Up to 2 years

Secondary Outcomes (6)

• OS

  Up to 2 years

• EFS

  Up to 2 years

• RFS

  Up to 2 years

• Time to CR/CRi

  Up to 2 years

• Duration of CR/CRi

  Up to 2 years

Study Arms (2)

DAC5

EXPERIMENTAL

Glasdegib will be administered at the starting dose of 100 mg orally once daily and continuously in combination with either DAC5 (decitabine 20 mg/m2 IV on a 5-day schedule) or DAC10 (decitabine 20 mg/m2 IV on a 10-day schedule) as per randomization. Treatment will be administered in 28-day cycles.

Drug: Glasdegib; Drug: Decitabine

DAC10

EXPERIMENTAL

Glasdegib will be administered at the starting dose of 100 mg orally once daily and continuously in combination with either DAC5 (decitabine 20 mg/m2 IV on a 5-day schedule) or DAC10 (decitabine 20 mg/m2 IV on a 10-day schedule) as per randomization. Treatment will be administered in 28-day cycles.

Drug: Glasdegib; Drug: Decitabine

Interventions

Glasdegib DRUG

Glasdegib will be administered at the starting dose of 100 mg orally once daily.

DAC10; DAC5

Decitabine DRUG

Decitabine will be administered per local label and will be administered by IV infusion at a dose of 20 mg/m2/day for either 5 days or 10 days as determined by randomization. Each cycle will be every 28 days.

DAC10; DAC5

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have a morphologically-confirmed diagnosis of AML according to WHO 2016 classification with poor-risk disease as defined by the cytogenetic or molecular abnormalities (excluding FLT3-mutated AML).
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤2.
• Adequate Renal Function:
• a. Calculated creatinine clearance (determined by MDRD) ≥50mL/min/1.73m2, or serum creatinine \<1.5x upper limit of normal (ULN);
• Adequate Liver Function:
• Total serum bilirubin ≤ 2.0 x ULN (unless the bilirubin is principally unconjugated and there is strong suspicion of sub-clinical hemolysis or the patient has documented Gilbert's disease);
• Aspartate transaminase (AST) and Alanine transaminase (ALT) ≤ 3.0 x ULN;
• Alkaline phosphatase ≤ 3.0 x ULN.
• Serum or urine pregnancy test (for female patients of childbearing potential) with a minimum sensitivity of 25 IU/L or equivalent units of human chorionic gonadotropin (HCG) negative at screening.
• Males and female patients both of childbearing potential and at risk for pregnancy must agree to use two highly effective method(s) of contraception throughout the study and for 180 days after the last dose of decitabine and the last dose of glasdegib, whichever occurs later.
• Female patients who are not of childbearing potential (i.e. meet at least 1 of the following criteria):
• Have undergone a documented hysterectomy and/or bilateral oophorectomy;
• Have medically confirmed ovarian failure;
• Have achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; status may be confirmed by having a serum follicle stimulating hormone (FSH) level within the laboratory's reference range for postmenopausal women.

You may not qualify if:

• Patients who are candidates for and willing to receive intensive induction chemotherapy.
• Prior use of a hypomethylating agent.
• Prior use of cytotoxic chemotherapy for any myeloid malignancy (prior immunosuppressive therapy is permitted provided that treatment is stopped within 8 weeks from study entry; hydroxyurea is allowed through the end of cycle 1 on study).
• Previous hematopoietic stem cell transplant.
• Prior treatment with a licensed or experimental smoothened inhibitor (SMOi) and/or hypomethylating agent (HMA).
• Participation in a clinical study involving an investigational drug(s) (Phases 1-4) within 4 weeks prior to study entry or within 5 half-lives of the investigational agent, whichever is greater.
• Major surgery or radiation within 12 weeks prior to study entry.
• Patients known to be refractory to platelet or packed red cell transfusions as per institutional guidelines, or who are known to refuse or who are likely to refuse blood product support.
• Treatment with hematopoietic growth factors including: erythropoietin, granulocyte colony stimulating factor (G-CSF), and granulocyte macrophage colony stimulating factor (GM-CSF), or thrombopoietin receptor agonists within 3 weeks prior to study entry.
• Any ongoing medical condition requiring chronic use of moderate to high dose steroids (defined as ≥10 mg/day of prednisone or equipotent dose of another corticosteroid).
• Any anti-cancer treatment within 2 weeks prior to study entry (including hydroxyurea as above).
• Current use or anticipated requirement for drugs that are known moderate to strong CYP3A4 inducers (Appendix 2).
• Presence of concurrent active malignancy requiring active systemic therapy
• Patients with known active, uncontrolled bacterial, fungal or viral infection, including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS) related illness.
• Known uncontrolled central nervous system (CNS) involvement.

Sponsors & Collaborators

• Yale University: lead
• Pfizer: collaborator

Study Sites (1)

Yale Cancer Center/Smilow

New Haven, Connecticut, 06511, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

glasdegib; Decitabine

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Azacitidine; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Dr. Amer Zeidan
• Organization: Yale University

amer.zeidan@yale.edu

(203) 200-4363

Study Officials

• Amer M Zeidan, MBBS

  Yale University - MEDCCC Hematology-Section

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Internal Medicine (Hematology)

Study Record Dates

• First Submitted: August 7, 2019
• First Posted: August 9, 2019
• Study Start: December 6, 2019
• Primary Completion: June 9, 2020
• Study Completion: June 9, 2020
• Last Updated: October 15, 2021
• Results First Posted: October 15, 2021

Record last verified: 2021-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)