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.
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
Interventions
Drug | Synonyms | Arms |
---|
PF-04449913 | | Continuation Cohort |
PF-04449913 | | Combination Cohort 1 |
Low dose ARA-C (LDAC) | | Combination Cohort 1 |
PF-04449913 | | Combination Cohort 2 |
Daunorubicin | | Combination Cohort 2 |
Cytarabine | | Combination Cohort 2 |
PF-04449913 | | Azacitidine Combination Cohort |
Azacitidine | | Azacitidine Combination Cohort |
PF-04449913 | | Expansion Cohort of LDAC Combination for Efficacy |
LDAC | | Expansion 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
Name | Type | Description | Interventions |
---|
Monotherapy Cohort | Experimental | PF-04449913 Monotherapy | |
Combination Cohort 1 | Experimental | PF-04449913 in combination with low dose ARA-C (LDAC) | - PF-04449913
- Low dose ARA-C (LDAC)
|
Combination Cohort 2 | Experimental | PF-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 Cohort | Experimental | PF-04449913 in combination with azacitidine | |
Continuation Cohort | Experimental | PF-04449913 Monotherapy for one patient rolled-over from another trial in the same project. | |
Expansion Cohort of LDAC Combination for Efficacy | Experimental | PF-04449913 in combination with LDAC to evaluate efficacy | |
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
Last Updated
March 12, 2021