PF-04449913 For Patients With Acute Myeloid Leukemia at High Risk of Relapse After Donor Stem Cell Transplant

NCT01841333 | Completed Phase 2 Results DMC

• 2 other identifiers: 12-1558.ccNCI-2013-00824
• Study Type: interventional
• Target: 31
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial will test whether the Hedgehog signaling pathway inhibitor PF-04449913 can decrease disease relapse in high-risk patients with acute myeloid leukemia after donor stem cell transplant.

Conditions

Adult Acute Myeloid Leukemia in Remission; Recurrent Adult Acute Myeloid Leukemia

Keywords

Myeloid leukemia in remission; Recurrent myeloid leukemia

Outcome Measures

Primary Outcomes (1)

• Relapse-free Survival in Days

  Days after transplant until disease relapse or death as measured by Kaplan-Meier statistical method.

  1 year

Secondary Outcomes (3)

• Remission Duration

  Up to 5 years

• Number of Patients With Adverse Events (AE) Related to Glasdegib

  30 days

• Overall Survival of All Patients

  1 year

Study Arms (1)

PF-04449913

EXPERIMENTAL

Beginning 80 days after allogeneic stem cell transplant, patients receive PF-04449913 (100mg) orally once daily on days 1-28. Treatment repeats every 28 days for up to 1 year in the absence of disease progression or unacceptable toxicity.

Drug: PF-04449913

Interventions

PF-04449913 DRUG

100mg given orally

Also known as: Hedgehog inhibitor

PF-04449913

Eligibility Criteria

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

You may qualify if:

• WHO-confirmed AML
• Age ≥18 years
• Between days 28 and 50 post transplantation at the time of initiation of the study drug
• ECOG performance status ≤ 2 (See Appendix A: ECOG Performance Status Scale)
• Life expectancy \> 2 months
• Recipient of a myeloablative or non-myeloablative allogeneic HSCT
• Conditioning regimen to be prescribed at investigator's discretion, but will be prospectively defined as myeloablative or non-myeloablative
• Stable engraftment, as defined by absolute neutrophil count (ANC) ≥ 1000/mm3 and platelets ≥ 25,000/mm3
• In morphologic remission (\< 5% marrow blasts) based on BM biopsy performed +/- 5 days of day 28 post- transplantation
• Without clinical signs of active central nervous system disease
• For non-myeloablative transplants, ≥50% CD3 donor chimerism at screening
• High risk of relapse after HSCT, defined as the presence of minimal residual disease as measured by flow cytometry in the absence of evidence of morphologic disease on a bone marrow biopsy prior to HSCT
• Adequate organ function as indicated by the following laboratory values:
• Aspartate aminotransferase (AST), alanine aminotransferase, (ALT) ≤ 3.0 x institutional upper limit of normal (ULN)
• Total bilirubin ≤ 2.0 x institutional ULN, unless documented Gilbert's syndrome

You may not qualify if:

• Concomitant treatment with other anti-neoplastic agents, with the exception, when clinically indicated, of prophylaxis in the post-transplantation setting with intrathecal chemotherapy
• Use of any other experimental drug or therapy within 28 days of baseline
• Inability to swallow or absorb drug
• Active uncontrolled acute fungal, bacterial, or other infection that is unresponsive to therapy at time of study drug dosing
• Unstable angina pectoris
• New York Heart Association Class III or IV heart failure
• QTc interval (using Fridericia's correction formula, QTcF, if prolonged) \>470 msec
• Active cardiac arrhythmias with rapid ventricular response (defined as heart rate greater than 100 beats/minute)
• Known HIV infection
• Grade III/IV acute GVHD
• Current use or anticipated need for food or drugs that are known moderate/strong CYP3A4 inducers (See Table 1 and section 5.9.2: Prohibited Concomitant Therapy), with the exception of azole antifungals, which are permitted.
• Any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures.
• Pregnant or lactating females

Sponsors & Collaborators

• University of Colorado, Denver: lead
• The Leukemia and Lymphoma Society: collaborator

Study Sites (2)

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia, Myeloid

Interventions

glasdegib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Daniel Pollyea
• Organization: University of Colorado

DANIEL.POLLYEA@cuanschutz.edu

720-848-8084

Study Officials

• Daniel A Pollyea, MD, MS

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2013
• First Posted: April 26, 2013
• Study Start: April 29, 2013
• Primary Completion: May 8, 2019
• Study Completion: February 4, 2020
• Last Updated: January 25, 2022
• Results First Posted: January 25, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)