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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02038777
Recruitment Status : Active, not recruiting
First Posted : January 17, 2014
Last Update Posted : June 11, 2020
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: PF-04449913 Drug: Low dose ARA-C (LDAC) Drug: Daunorubicin Drug: Cytarabine Drug: Azacitidine Drug: LDAC Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 48 participants
Allocation: Non-Randomized
Intervention Model Description: MTD was determined in monotherapy cohort. Then two combination cohorts (Combination Cohorts 1 and 2) were added to evaluate the safety of glasdegib administered with chemotherapies. Another combination cohort (Combination Cohort 3) was added to evaluate the safety of glasdegib administered with Azacitidine. Then, Continuation Cohort which allows one Japanese patient enrolled from another trial in the same project was added. Afther that, Expansion Cohort of LDAC Combination for efficacy was added.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 25, 2014
Estimated Primary Completion Date : November 3, 2020
Estimated Study Completion Date : January 31, 2021


Arm Intervention/treatment
Experimental: Monotherapy Cohort
PF-04449913 Monotherapy
Drug: PF-04449913
PF-04449913 administered orally and continuously in 28 day cycles.

Experimental: Combination Cohort 1
PF-04449913 in combination with low dose ARA-C (LDAC)
Drug: PF-04449913
PF-04449913 administered orally and continuously in 28 day cycles.

Drug: Low dose ARA-C (LDAC)
Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.

Experimental: Combination Cohort 2
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.
Drug: PF-04449913
PF-04449913 administered orally and continuously in 28 day cycles.

Drug: Daunorubicin
Daunorubicin given using 60 mg/m2 for 3-days.

Drug: Cytarabine
Cytarabine 100 mg/m2 on days 1 through 7.

Experimental: Azacitidine Combination Cohort
PF-04449913 in combination with azacitidine
Drug: PF-04449913
PF-04449913 administered orally and continuously in 28 day cycles.

Drug: Azacitidine
Azacitidine Combination Cohort; Azacitidine 75 mg/m2 for 7 days.

Experimental: Continuation Cohort
PF-04449913 Monotherapy for one patient rolled-over from another trial in the same project.
Drug: PF-04449913
PF-04449913 administered orally and continuously in 28 day cycles.

Experimental: Expansion Cohort of LDAC Combination for Efficacy
PF-04449913 in combination with LDAC to evaluate efficacy
Drug: PF-04449913
PF-04449913 administered orally and continuously in 28 day cycles.

Drug: LDAC
Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.




Primary Outcome Measures :
  1. First cycle Dose Limiting Toxicities [ Time Frame: 28 days after first dose ]
  2. Disease Modifying Response Rate [ Time Frame: At the beginning of Cycle 9 (each cycle is 28 days). ]
    For the Expansion Cohort of LDAC Combination for efficacy only


Secondary Outcome Measures :
  1. Maximum observed plasma concentration (Cmax) [ Time Frame: 12 months ]
  2. Time to reach maximum observed plasma concentration (Tmax) [ Time Frame: 12 months ]
  3. Area under the plasma concentration curve (AUC) [ Time Frame: 12 months ]
  4. Objective disease response [ Time Frame: 12 months ]
  5. Disease-related gene mutation (PD biomarkers) [ Time Frame: 12 months ]
  6. Detectable tumor Gli1 expression (PD Biomarkers) [ Time Frame: 12 months ]
  7. Overall Survival (OS) [ Time Frame: 3 years ]
    For Azacitidine Combination Cohort and Expansion Cohort of LDAC Combination for Efficacy only

  8. Probability of Participant Survival [ Time Frame: 1 years ]
    For Combination Cohort 1 only



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02038777


Locations
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Japan
Japanese Red Cross Nagoya First Hospital
Nagoya, Aichi, Japan, 453-8511
Kobe University Hospital
Kobe-shi, Hyogo, Japan, 650-0017
Tohoku University Hospital
Sendai, Miyagi, Japan, 980-8574
Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital
Bunkyo-ku, Tokyo, Japan, 113-8677
National Cancer Center Hospital
Chuo-ku, Tokyo, Japan, 104-0045
Yamagata University Hospital
Yamagata-Shi, Yamagata, Japan, 990-9585
Akita University Hospital
Akita, Japan, 010-8543
Kyushu University Hospital
Fukuoka, Japan, 812-8582
Tokyo Medical University Hospital
Tokyo, Japan, 160-0023
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02038777    
Other Study ID Numbers: B1371005
First Posted: January 17, 2014    Key Record Dates
Last Update Posted: June 11, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Pfizer:
Hematologic Malignancies
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Hematologic Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Hematologic Diseases
Cytarabine
Azacitidine
Daunorubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Enzyme Inhibitors
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors