Phase I Epigenetic Priming Using Decitabine With Induction Chemotherapy in AML

This study has been completed.
Sponsor:
Collaborator:
Eisai Inc.
Information provided by:
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00538876
First received: October 2, 2007
Last updated: June 29, 2011
Last verified: June 2011
  Purpose

This is an open label phase I study designed to explore the feasibility, safety and biologic activity of epigenetic priming with decitabine prior to standard cytarabine, daunorubicin induction chemotherapy in younger patients with less-than-favorable risk AML.

Primary Objective: To find an appropriate dose level for decitabine when used as priming for cytarabine and daunorubicin "7+3" induction chemotherapy in AML.

Secondary Objectives:

  1. To establish the safety and expected toxicities of decitabine when used as priming for cytarabine and daunorubicin "7+3" induction chemotherapy in AML.
  2. To establish the optimal dose schedule of decitabine required to broadly demethylate cytosine residues in genomic regulatory regions.
  3. To investigate, in selected cases, the molecular and cellular consequences of decitabine-induced hypomethylation by a) establishing the extent and degree of hypomethylation at specific genomic loci required to reactivate the expression of repressed genes and by b) determining the effect of hypomethylation on the differentiation and/or apoptosis of leukemic blasts.

Condition Intervention Phase
Acute Myeloid Leukemia
Drug: decitabine
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Epigenetic Priming Using Decitabine With Induction Chemotherapy in Patients With Acute Myelogenous Leukemia (AML)

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • To establish the safety and expected toxicities of decitabine when used as priming for cytarabine and daunorubicin "7+3" induction chemotherapy in AML [ Time Frame: duration of study ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 30
Study Start Date: July 2007
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: decitabine
    Decitabine will be administered by intravenous injection at a dose of 20 mg/m2/day as a daily 1hr infusion (Arm A) or by continuous infusion (Arm B) for 3, 5 or 7 days. On the day following the final dose of decitabine, standard "7+3" induction chemotherapy will begin.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed diagnosis of Acute Myelogenous Leukemia (AML)
  • Patient is >18 and ≤ 60 years of age.
  • AML subgroup is associated with less-than-favorable risk as defined by:

    • The absence of good risk molecular features: t(8;21), inv(16), t(16;16), or t(15;17) translocations identified by FISH or standard metaphase karyotyping or evidence for the corresponding fusion transcripts, AML1-ETO, CBFβ-SMMHC, or PML-RARα, as identified by RT-PCR or suggested by the FAB M3 phenotype;
    • A history of an antecedent myelodysplastic syndrome;
    • A history of an antecedent Philadelphia-chromosome negative myeloproliferative disorder (e.g., polycythemia vera, essential thrombocythemia, primary myelofibrosis);
    • Treatment-related AML believed secondary to prior cytotoxic chemotherapy for an unrelated disease.
  • Patient has adequate cardiac function as defined by:

    • An echocardiogram or MUGA scan demonstrating an ejection fraction within normal limits.
  • ECOG performance status > = 2.
  • Patient has adequate hepatic/renal function as defined by:

    • Total bilirubin ≤ 2 mg/dL. Patients with documented evidence of Gilbert's Syndrome resulting in elevated total bilirubin levels will be eligible, provided all other eligibility criteria are met.
    • Aspartate transaminase (AST) and alanine transaminase (ALT) ≤1.5 x the ULN.
    • Creatinine ≤ 2 mg/dL (or a creatinine clearance >50 mL/min/1.73 m2, by direct measure).
  • Patient is not childbearing:

    • Female subjects must be surgically sterile, postmenopausal, or have a β-HCG indicating that they are not pregnant at the time screening is performed.
    • Female patients of childbearing potential must agree to take appropriate measures to ensure that they do not become pregnant while enrolled on protocol (i.e., within 2 months of administration of chemotherapy).
    • Male patients must agree to take appropriate measures to ensure that they do not father a child while enrolled on protocol (i.e., within 2 months following administration of chemotherapy).
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • AML with "good risk" molecular features: karyotype demonstrating the presence of t(8;21), inv(16), t(16;16), or t(15;17) translocations identified by FISH or standard metaphase karyotyping or evidence for the corresponding fusion transcripts, AML1-ETO, CBFβ-SMMHC, or PML-RARα, as identified by RT-PCR or suggested by the FAB M3 phenotype.
  • Patient has a history of chronic myelogenous leukemia or has molecular evidence of the t(9;22) translocation by FISH, metaphase karyotype or RT-PCR for the BCR-ABL fusion transcript.
  • Patient has received chemotherapy (other than hydroxyurea) or radiation within the 2 weeks prior to planned therapy on this study.
  • Patient has an active second malignancy.
  • Patient has a medical condition or illness considered by the Investigator to constitute an unwarranted high risk for investigational drug treatment.
  • Patient has an uncontrolled serious infection.
  • Patient is pregnant or nursing an infant.
  • Patient has a psychiatric disorder or altered mental status that would preclude understanding of the informed consent process and/or completion of the necessary studies.
  • Patient has an inability or unwillingness, in the opinion of the Investigator, to comply with the protocol requirements.
  • Patients with central nervous system (CNS) (or leptomeningeal) involvement by their AML may be considered for treatment at the Investigator's discretion and following discussion with the Medical Monitor, in order to allow for appropriate management.
  • Patient has circulating blast count > 50,000/μL (patients may be enrolled if circulating blast count is controlled by hydroxyurea and/or, if clinically indicated, by leukopheresis).
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00538876

Locations
United States, New York
Weill Medical College of Cornell University
New York, New York, United States, 10021
Sponsors and Collaborators
Weill Medical College of Cornell University
Eisai Inc.
Investigators
Principal Investigator: Joseph Scandura, MD Weill Medical College of Cornell University
  More Information

Additional Information:
Publications:
Responsible Party: Joseph Scandura, MD, Weill Cornell Medical College
ClinicalTrials.gov Identifier: NCT00538876     History of Changes
Other Study ID Numbers: 0704009108
Study First Received: October 2, 2007
Last Updated: June 29, 2011
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms
Neoplasms by Histologic Type
Decitabine
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014