A Study Of PF-04449913 In Select Hematologic Malignancies

NCT00953758 | Completed Phase 1 Results

• 2 other identifiers: B13710012009-011285-29
• Study Type: interventional
• Target: 47
• Locations: 2 countries
• Sites: 6

Brief Summary

This study examines the effect of a small molecule inhibitor to the Sonic Hedgehog pathway on select hematologic malignancies.

Conditions

Hematologic Malignancies

Keywords

Chronic Myeloid Leukemia Myelofibrosis Myelodysplastic Syndrome Acute myeloid Leukemia Hedgehog inhibitor

Outcome Measures

Primary Outcomes (1)

• Number of Participants With First Cycle Dose-limiting Toxicities (DLTs)

  Any DLT event in Cycle 1: 1) Grade \>=3 non-hematologic toxicity that had been maximally treated, 2) prolonged myelosupression that lasted greater than (\>) 42 days from the point of detection in a normal bone marrow (less than \[\<\] 500 per microliter \[/uL\] or platelet count \<10,000/uL, or hemoglobin \<8 gram per deciliter \[g/dL\] with \<5% blasts and no evidence of disease or dysplasia), 3) inability to deliver \>= 80% of the planned doses due to PF-04449913 related non-hematologic and hematologic toxicities

  Cycle 1 Day 1 to end of Cycle 1 (28 days)

Secondary Outcomes (30)

• Percentage of Participants With Treatment-emergent Adverse Events (AEs) by National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE) (Version 3.0) Grade

  Baseline up to 28 days post last dose of study medication (maximum duration: 537 days)

• Percentage of Participants With Treatment-related Adverse Events (AEs), by NCI CTCAE Version 3.0) Grade

  Baseline up to 28 days post last dose of study medication (maximum duration: 537 days)

• Number of Participants With Vital Signs Values Meeting Categorical Summarization Criteria

  Screening up to maximum of 537 days

• Number of Participants With Laboratory Test Abnormalities

  Screening to EOT (maximum duration: 537 days)

• Hedgehog Biomarker Modulation: Relative GLI1 Gene Expression to Baseline for Normal Skin on Cycle 1 Day 21

  Baseline, Cycle 1 Day 21

Study Arms (1)

1

EXPERIMENTAL

Drug: PF-04449913

Interventions

PF-04449913 DRUG

Escalating doses of PF-04449913 administered as tablets PO QD continuously in 28 day cycles

1

Eligibility Criteria

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

You may qualify if:

• Patients with select advanced hematologic malignancies who are refractory, resistant or intolerant to prior therapies. They may be newly diagnosed and previously untreated, but not eligible for standard treatment options, or for whom standard therapies are not anticipated to result in a durable response.
• ECOG performance status 0 to 2
• Adequate organ function

You may not qualify if:

• Patients with active CNS disease
• Patient with active malignancy with the exception of basal cell carcinoma, non melanoma skin cancer, carcinoma in situ cervical or skin cancer
• Active GVHD other than Grade 1 skin involvement
• Known malabsorption syndrome
• Patient has an active, life threatening or clinically significant uncontrolled systemic infection

Sponsors & Collaborators

• Pfizer: lead

Study Sites (6)

UCSD Medical Center - La Jolla

La Jolla, California, 92037, United States

Location

Moores UCSD Cancer Center

La Jolla, California, 92093, United States

Location

UCSD Medical Center - Hillcrest

San Diego, California, 92103, United States

Location

The University of Texas M.D. Anderson Cancer Center

Houston, Texas, 77030-4009, United States

Location

University of Washington Medical Center, Seattle Cancer Care Alliance

Seattle, Washington, 98109-1023, United States

Location

U.O. di Ematologia

Bologna, 40138, Italy

Location

Related Publications (2)

• Fostvedt LK, Shaik N, Martinelli G, Wagner AJ, Ruiz-Garcia A. Exposure-response modeling of the effect of glasdegib on cardiac repolarization in patients with cancer. Expert Rev Clin Pharmacol. 2021 Jul;14(7):927-935. doi: 10.1080/17512433.2021.1925538. Epub 2021 May 18.

  PMID: 33993815 DERIVED

• Martinelli G, Oehler VG, Papayannidis C, Courtney R, Shaik MN, Zhang X, O'Connell A, McLachlan KR, Zheng X, Radich J, Baccarani M, Kantarjian HM, Levin WJ, Cortes JE, Jamieson C. Treatment with PF-04449913, an oral smoothened antagonist, in patients with myeloid malignancies: a phase 1 safety and pharmacokinetics study. Lancet Haematol. 2015 Aug;2(8):e339-46. doi: 10.1016/S2352-3026(15)00096-4. Epub 2015 Jul 26.

  PMID: 26688487 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

glasdegib

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Limitations and Caveats

Some participants were administered the lead-in dose at other times (other than Day -6 as stated) due to changes in the timing of the lead-in dose as the protocol was amended a few times.

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2009
• First Posted: August 6, 2009
• Study Start: March 3, 2010
• Primary Completion: September 26, 2012
• Study Completion: February 27, 2013
• Last Updated: April 25, 2024
• Results First Posted: April 25, 2024

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (5); IT (1)