Clinical Trials /

A Study Of PF-04449913 In Japanese Patients With Select Hematologic Malignancies

NCT02038777

Description:

This is an open-label, multi-center, Phase 1 study of PF-04449913 in Japanese patients. PF-04449913 will be administered orally as a single agent in patients with select advanced hematologic malignancies, or in combination with LDAC [Low-Dose Ara-C] or cytarabine and daunorubicin in previously untreated patients with AML [Acute Myeloid Leukemia] or high-risk MDS [Myelodysplastic Syndrome], or in combination with azacitidine in previously untreated patients with AML.

Related Conditions:
  • Acute Myeloid Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

URL:

https://clinicaltrials.gov/show/NCT02038777

Trial Eligibility

Document

Title

  • Brief Title: A Study Of PF-04449913 In Japanese Patients With Select Hematologic Malignancies
  • Official Title: A PHASE 1 STUDY TO EVALUATE THE SAFETY, TOLERABILITY, EFFICACY, PHARMACOKINETICS, AND PHARMACODYNAMICS OF PF-04449913 (GLASDEGIB), AN ORAL HEDGEHOG INHIBITOR, ADMINISTERED AS A SINGLE AGENT IN JAPANESE PATIENTS WITH SELECT HEMATOLOGIC MALIGNANCIES AND IN COMBINATION WITH INTENSIVE CHEMOTHERAPY, LOW-DOSE ARA-C, OR AZACITIDINE IN PATIENTS WITH ACUTE MYELOID LEUKEMIA OR HIGH-RISK MYELODYSPLASTIC SYNDROME

Clinical Trial IDs

  • ORG STUDY ID: B1371005
  • NCT ID: NCT02038777

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
PF-04449913Continuation Cohort
PF-04449913Combination Cohort 1
Low dose ARA-C (LDAC)Combination Cohort 1
PF-04449913Combination Cohort 2
DaunorubicinCombination Cohort 2
CytarabineCombination Cohort 2
PF-04449913Azacitidine Combination Cohort
AzacitidineAzacitidine Combination Cohort
PF-04449913Expansion Cohort of LDAC Combination for Efficacy
LDACExpansion Cohort of LDAC Combination for Efficacy

Purpose

This is an open-label, multi-center, Phase 1 study of PF-04449913 in Japanese patients. PF-04449913 will be administered orally as a single agent in patients with select advanced hematologic malignancies, or in combination with LDAC [Low-Dose Ara-C] or cytarabine and daunorubicin in previously untreated patients with AML [Acute Myeloid Leukemia] or high-risk MDS [Myelodysplastic Syndrome], or in combination with azacitidine in previously untreated patients with AML.

Trial Arms

NameTypeDescriptionInterventions
Monotherapy CohortExperimentalPF-04449913 Monotherapy
  • PF-04449913
Combination Cohort 1ExperimentalPF-04449913 in combination with low dose ARA-C (LDAC)
  • PF-04449913
  • Low dose ARA-C (LDAC)
Combination Cohort 2ExperimentalPF-04449913 in combination with intensive chemotherapy: PF-04449913 administered continuously for 28 days. Daunorubicin given using 60 mg/m2 for 3-days together with cytarabine 100 mg/m2 on days 1 through 7 followed by cytarabine 1g/m2 on days 1, 3, and 5 during 2-4 cycles of consolidation therapy.
  • PF-04449913
  • Daunorubicin
  • Cytarabine
Azacitidine Combination CohortExperimentalPF-04449913 in combination with azacitidine
  • PF-04449913
  • Azacitidine
Continuation CohortExperimentalPF-04449913 Monotherapy for one patient rolled-over from another trial in the same project.
  • PF-04449913
Expansion Cohort of LDAC Combination for EfficacyExperimentalPF-04449913 in combination with LDAC to evaluate efficacy
  • PF-04449913
  • LDAC

Eligibility Criteria

        Inclusion Criteria:

          -  Patients with select advanced hematologic malignancies who are refractory, resistant
             or intolerant to prior therapies for monotherapy cohort.

          -  Patients with AML or High-Risk MDS who are newly diagnosed and previously untreated
             for combination cohort.

          -  Patients with AML who are newly diagnosed and previously untreated for azacitidine
             combination cohort.

          -  ECOG [Eastern Cooperative Oncology Group] performance status 0 to 2

          -  Adequate organ function

        Exclusion Criteria:

          -  Patients with active CNS disease

          -  Patient with active malignancy with the exception of basal cell carcinoma, non
             melanoma skin cancer, carcinoma in situ cervical

          -  Patient has an active, life threatening or clinically significant uncontrolled
             systemic infection
Maximum Eligible Age:N/A
Minimum Eligible Age:20 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:First cycle Dose Limiting Toxicities
Time Frame:28 days after first dose
Safety Issue:
Description:For the Expansion Cohort of LDAC Combination for efficacy only

Secondary Outcome Measures

Measure:Maximum observed plasma concentration (Cmax)
Time Frame:12 months
Safety Issue:
Description:
Measure:Time to reach maximum observed plasma concentration (Tmax)
Time Frame:12 months
Safety Issue:
Description:
Measure:Area under the plasma concentration curve (AUC)
Time Frame:12 months
Safety Issue:
Description:
Measure:Objective disease response
Time Frame:12 months
Safety Issue:
Description:
Measure:Disease-related gene mutation (PD biomarkers)
Time Frame:12 months
Safety Issue:
Description:
Measure:Detectable tumor Gli1 expression (PD Biomarkers)
Time Frame:12 months
Safety Issue:
Description:
Measure:Overall Survival (OS)
Time Frame:3 years
Safety Issue:
Description:For Azacitidine Combination Cohort and Expansion Cohort of LDAC Combination for Efficacy only
Measure:Probability of Participant Survival
Time Frame:1 years
Safety Issue:
Description:For Combination Cohort 1 only

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Active, not recruiting
Lead Sponsor:Pfizer

Trial Keywords

  • Hematologic Malignancies

Last Updated

March 12, 2021