A Study To Evaluate PF-04449913 With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome
This study is currently recruiting participants.
Verified May 2013 by Pfizer
Sponsor:
Pfizer
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01546038
First received: March 1, 2012
Last updated: May 6, 2013
Last verified: May 2013
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Purpose
This is a study to evaluate PF-04449913 (an inhibitor of the Hedgehog pathway) in Acute Myeloid Leukemia and high-risk Myelodysplastic Syndrome in combination with standard agents used to treat these diseases.
| Condition | Intervention | Phase |
|---|---|---|
|
Acute Myeloid Leukemia |
Drug: PF-04449913 Drug: Low dose ARA-C (LDAC) Drug: Decitabine Drug: Daunorubicin Drug: Cytarabine Drug: Pf-04449913 |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | A Phase 1B/2 Study To Evaluate The Safety And Efficacy Of PF-04449913, An Oral Hedgehog Inhibitor, In Combination With Intensive Chemotherapy, Low Dose Ara-C Or Decitabine In Patients With Acute Myeloid Leukemia Or High Risk Myelodysplastic Syndrome |
Resource links provided by NLM:
Drug Information available for:
Cytarabine
Decitabine
Daunorubicin
Daunorubicin hydrochloride
Daunorubicin citrate
U.S. FDA Resources
Further study details as provided by Pfizer:
Primary Outcome Measures:
- Number of participants with Dose-limiting toxicities (DLT) [ Time Frame: 1 -year ] [ Designated as safety issue: Yes ]
- Percentage of patients with Complete Response rate [ Time Frame: 2-years ] [ Designated as safety issue: No ]
- Overall Survival (OS) [ Time Frame: 48 months ] [ Designated as safety issue: No ]
Secondary Outcome Measures:
- Area Under the Curve from Time Zero to end of dosing interval (AUCtau) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Overall Survival (OS) [ Time Frame: 48 months ] [ Designated as safety issue: No ]
- Percentage of patients with disease-specific efficacy for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Percentage of patients with Complete Response rate / Complete Response rate with incomplete blood count recovery [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Cumulative incidence of relapse (CIR), relapse free survival (RFS), event free survival (EFS), and cumulative incidence of death (CID) [ Time Frame: 48 months ] [ Designated as safety issue: No ]
- QTc Interval [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
- Disease-related gene mutation (PD biomarkers) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Changes in analyte levels from baseline to post-treatment (PD biomarkers) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Changes in gene levels from baseline to post-treatment (PD biomarkers) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Detectable tumor Gli1 expression (PD Biomarkers) [ Time Frame: 2 years ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 265 |
| Study Start Date: | July 2012 |
| Estimated Study Completion Date: | April 2016 |
| Estimated Primary Completion Date: | June 2013 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Arm A (Phase 1B)
PF-04449913 in combination with low dose ARA-C (LDAC)
|
Drug: PF-04449913
PF-04449913 administered orally and continuously for 28-days.
Drug: Low dose ARA-C (LDAC)
Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.
|
|
Experimental: Arm B (Phase 1B)
PF-04449913 in combination with Decitabine
|
Drug: PF-04449913
PF-04449913 administered orally and continuously for 28 days.
Drug: Decitabine
Decitabine given at 20 mg/m2 over 1 hour infusion for 5-days
|
|
Experimental: Arm C (Phase 1B)
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 for 28 days
Drug: Daunorubicin
Daunorubicin given using 60 mg/m2 for 3-days
Drug: Cytarabine
Cytarabine 100 mg/m2 on days 1 through 7
|
|
Experimental: P2 Fit (Phase 2 Single Arm)
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 for 28 days
Drug: Daunorubicin
Daunorubicin given using 60 mg/m2 for 3-days
Drug: Cytarabine
Cytarabine 100 mg/m2 on days 1 through 7
|
|
P2 Unfit (Phase 2 Randomized)
Patients will be randomized 2:1 (low dose ARA-C in combination with PF-04449913: low dose ARA-C alone).
|
Drug: PF-04449913
PF-04449913 administered orally and continuously for 28 days (if randomized to receive PF-04449913)
Drug: Low dose ARA-C (LDAC)
Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10.
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- Patients with AML or RAEB 2 High Risk MDS who are newly diagnosed according to the WHO 2008 Classification and previously untreated.
- Patients with AML (arising from an antecedent hematologic disease [AHD]) or MDS who may have had one prior regimen with commercially available agents for the treatment of their prior hematologic disease. The patients may not have had a prior therapy for their AML.
- AML patients include de novo AML, AML evolving from MDS or other AHD and AML after previous cytotoxic therapy or radiation (secondary AML)
- For a diagnosis of AML, a bone marrow blast count of 20% or more is required.
- For a diagnosis of high-risk Myelodysplastic Syndrome RAEB 2 the patient must have 10-19% bone marrow blasts
- Adequate Organ Function
- ECOG Performance Status 0, 1, or 2
Exclusion Criteria:
- AML M3 Acute Promyelocytic Leukemia (APL) or patients with a t(9:22) cytogenetic translocation.
- Patients in whom, at the time of study entry, a stem cell transplant is planned within the next 6 months.
- Patients with known active uncontrolled central nervous system (CNS) leukemia.
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01546038
Contacts
| Contact: Pfizer CT.gov Call Center | 1-800-718-1021 | |
| Contact: Pfizer Oncology Clinical Trial Information Service | 1-877-369-9753 | PfizerCancerTrials@emergingmed.com |
Locations
| United States, Colorado | |
| Pfizer Investigational Site | Recruiting |
| Aurora, Colorado, United States, 80045 | |
| United States, Florida | |
| Pfizer Investigational Site | Recruiting |
| Tampa, Florida, United States, 33612 | |
| United States, Illinois | |
| Pfizer Investigational Site | Recruiting |
| Chicago, Illinois, United States, 60611 | |
| Pfizer Investigational Site | Recruiting |
| Chicago, Illinois, United States, 60637 | |
| United States, Kansas | |
| Pfizer Investigational Site | Not yet recruiting |
| Kansas City, Kansas, United States, 66160 | |
| Pfizer Investigational Site | Not yet recruiting |
| Westwood, Kansas, United States, 66205 | |
| United States, Massachusetts | |
| Pfizer Investigational Site | Not yet recruiting |
| Boston, Massachusetts, United States, 02215 | |
| United States, Michigan | |
| Pfizer Investigational Site | Recruiting |
| Ann Arbor, Michigan, United States, 48109 | |
| Pfizer Investigational Site | Recruiting |
| Detroit, Michigan, United States, 48201 | |
| United States, Missouri | |
| Pfizer Investigational Site | Recruiting |
| Saint Louis, Missouri, United States, 63110 | |
| Pfizer Investigational Site | Recruiting |
| Saint Louis, Missouri, United States, 63141 | |
| United States, New Jersey | |
| Pfizer Investigational Site | Recruiting |
| Hackensack, New Jersey, United States, 07601 | |
| United States, New York | |
| Pfizer Investigational Site | Recruiting |
| Buffalo, New York, United States, 14263 | |
| United States, Tennessee | |
| Pfizer Investigational Site | Recruiting |
| Nashville, Tennessee, United States, 37203 | |
| United States, Texas | |
| Pfizer Investigational Site | Recruiting |
| Houston, Texas, United States, 77030 | |
| United States, Washington | |
| Pfizer Investigational Site | Recruiting |
| Seattle, Washington, United States, 98109 | |
| Canada, Ontario | |
| Pfizer Investigational Site | Not yet recruiting |
| Hamilton, Ontario, Canada, L8V 1C3 | |
Sponsors and Collaborators
Pfizer
Investigators
| Study Director: | Pfizer CT.gov Call Center | Pfizer |
More Information
Additional Information:
No publications provided
| Responsible Party: | Pfizer |
| ClinicalTrials.gov Identifier: | NCT01546038 History of Changes |
| Other Study ID Numbers: | B1371003 |
| Study First Received: | March 1, 2012 |
| Last Updated: | May 6, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Pfizer:
|
Hedgehog Inhibitor Acute Myeloid Leukemia Myelodysplastic syndrome Intensive chemotherapy LDAC |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid, Acute Leukemia, Myeloid Myelodysplastic Syndromes Preleukemia Neoplasms by Histologic Type Neoplasms Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Cytarabine Decitabine Daunorubicin |
Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses Antiviral Agents Anti-Infective Agents Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antibiotics, Antineoplastic Enzyme Inhibitors |
ClinicalTrials.gov processed this record on May 22, 2013