A Study To Evaluate PF With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome

Transcription

1 A service of the U.S. National Institutes of Health Trial record 1 of 5 for: efficacy of PF Previous Study Return to List Next Study A Study To Evaluate PF With Chemotherapy In Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome This study is currently recruiting participants. (see Contacts and Locations) Verified October 2014 by Sponsor: Information prov ided by (Responsible Party): ClinicalTrials.gov Identifier: NCT First received: March 1, 2012 Last updated: October 30, 2014 Last verified: October 2014 History of Changes Full Text View Tabular View No Study Results Posted Disclaimer How to Read a Study Record Purpose This is a study to evaluate PF (an inhibitor of the Hedgehog pathw ay) in Acute Myeloid Leukemia and high-risk Myelodysplastic Syndrome in combination w ith standard agents used to treat these diseases. Condition Interv ention Phase Acute Myeloid Leukemia Drug: Decitabine Phase 1 Phase 2 Study Type: Study Design: Official Title: Interventional Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment A Phase 1B/2 Study To Evaluate The Safety And Efficacy Of PF , 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 prov ided by NLM: Genetics Home Reference related topics: core binding factor acute myeloid leukemia cytogenetically normal acute myeloid leukemia familial acute myeloid leukemia w ith mutated CEBPA MedlinePlus related topics: Acute Myeloid Leukemia Leukemia Myelodysplastic Syndromes Drug Information available for: Cytarabine Decitabine Daunorubicin Daunorubicin hydrochloride Daunorubicin citrate Genetic and Rare Diseases Information Center resources: Acute Myelocytic Leukemia Acute Non Lymphoblastic Leukemia Leukemia, Myeloid Myelodysplastic Syndromes U.S. FDA Resources Further study details as prov ided by :

2 Primary Outcome Measures: Number of participants w ith Dose-limiting toxicities (DLT) [ Time Frame: 1 -year ] [ Designated as safety issue: Yes ] (Phase 1B) Percentage of patients w ith Complete Response rate [ Time Frame: 2-years ] [ Designated as safety issue: No ] Complete response are those w ith repeat bone marrow show ing less than 5 percent (%) myeloblasts w ith normal peripheral blood values. (Phase 2 Fit) Overall Survival (OS) [ Time Frame: 48 months ] [ Designated as safety issue: No ] Time from the start of study treatment to date of death due to any cause. (Phase 2 Unfit) 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 ] Not Specified Overall Survival (OS) [ Time Frame: 48 months ] [ Designated as safety issue: No ] Time from the start of study treatment to date of death due to any cause. (Phase 1B; Phase 2 Fit) Percentage of patients w ith disease-specific efficacy for Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) [ Time Frame: 2 years ] [ Designated as safety issue: No ] (Phase 2 Fit and Unfit) Percentage of patients w ith Complete Response rate / Complete Response rate w ith incomplete blood count recovery [ Time Frame: 2 years ] [ Designated as safety issue: No ] Complete response are those w ith repeat bone marrow show ing less than 5 percent (%) myeloblasts w ith normal peripheral blood values. (Phase 1B; Phase 2 Unfit); Complete response w ith incomplete blood count recovery are those w ith repeat bone marrow show ing less than 5 percent (%) myeloblasts w ith either platelets or neutrophils not recovered. 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 ] RFS, CIR and CID are defined only for patients achieving CR or CRi (Phase 2 Fit and Unfit); EFS (P2 Fit only) is defined as the time from C1D-3 to date of induction treatment failure, or relapse from CR or CRi, or death from any cause. 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: September 2016 Estimated Primary Completion Date: September 2016 (Final data collection date for primary outcome measure)

3 Arms Experimental: Arm A (Phase 1B) PF in combination w ith low dose ARA-C (LDAC) Experimental: Arm B (Phase 1B) PF in combination w ith Decitabine Experimental: Arm C (Phase 1B) PF in combination w ith intensive chemotherapy: PF administered continuously for 28 days. Daunorubicin given using 60 mg/m2 for 3-days together w ith cytarabine 100 mg/m2 on days 1 through 7 follow ed by cytarabine 1g/m2 on days 1, 3, and 5 during 2-4 cycles of consolidation therapy. Experimental: P2 Fit (Phase 2 Single Arm) PF in combination w ith intensive chemotherapy: PF administered continuously for 28 days. Daunorubicin given using 60 mg/m2 for 3-days together w ith cytarabine 100 mg/m2 on days 1 through 7 follow ed by cytarabine 1g/m2 on days 1, 3, and 5 during 2-4 cycles of consolidation therapy. P2 Unfit (Phase 2 Randomized) Patients w ill be randomized 2:1 (low dose ARA-C in combination w ith PF : low dose ARA-C alone). Assigned Interv entions continuously for 28-days. Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10. continuously for 28 days. Drug: Decitabine Decitabine given at 20 mg/m2 over 1 hour infusion for 5-days continuously for 28 days Daunorubicin given using 60 mg/m2 for 3-days Cytarabine 100 mg/m2 on days 1 through 7 continuously for 28 days Daunorubicin given using 60 mg/m2 for 3-days Cytarabine 100 mg/m2 on days 1 through 7 continuously for 28 days (if randomized to receive PF ) Low dose ARA-C (LDAC) administered at 20 mg SQ, BID on Days 1 through 10. Eligibility Ages Eligible for Study: Genders Eligible for Study: Accepts Healthy Volunteers: 18 Years and older Both No Criteria Inclusion Criteria: Patients w ith AML or RAEB 2 High Risk MDS w ho are new ly diagnosed according to the WHO 2008 Classification and previously untreated. Patients w ith AML (arising from an antecedent hematologic disease [AHD]) or MDS w ho may have had one prior regimen w ith 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.

4 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 w ith a t(9:22) cytogenetic translocation. Patients w ith know n active uncontrolled central nervous system (CNS) leukemia. Contacts and Locations Choosing to participate in a study is an important personal decision. Talk w ith 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, see Learn About Clinical Studies. Please refer to this study by its ClinicalTrials.gov identifier: NCT Contacts Contact: CT.gov Call Center Show 62 Study Locations Sponsors and Collaborators Inv estigators Study Director: CT.gov Call Center More Information Additional Information: To obtain contact information for a study center near you, click here. No publications provided Responsible Party: ClinicalTrials.gov Identifier: NCT History of Changes Other Study ID Numbers: B Study First Received: March 1, 2012 Last Updated: October 30, 2014 Health Authority: United States: Food and Drug Administration Keyw ords provided by : Hedgehog Inhibitor Acute Myeloid Leukemia Myelodysplastic syndrome Intensive chemotherapy LDAC Additional relevant MeSH terms: Leukemia Leukemia, Myeloid Leukemia, Myeloid, Acute Myelodysplastic Syndromes Preleukemia Syndrome Bone Marrow Diseases Disease Hematologic Diseases Neoplasms Neoplasms by Histologic Type Pathologic Processes Precancerous Conditions Decitabine Anti-Infective Agents Antibiotics, Antineoplastic Antimetabolites Antimetabolites, Antineoplastic Antineoplastic Agents Antiviral Agents Enzyme Inhibitors Immunologic Factors Immunosuppressive Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Physiological Effects of Drugs

5 Cytarabine Daunorubicin Therapeutic Uses Topoisomerase II Inhibitors ClinicalTrials.gov processed this record on November 16, 2014