Phase 2 Study of Temozolomide to Treat Poor Risk / Refractory Acute Myeloid Leukemia

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. Identifier: NCT00611247
Recruitment Status : Completed
First Posted : February 8, 2008
Results First Posted : July 9, 2014
Last Update Posted : July 9, 2014
Information provided by (Responsible Party):
Bruno C. Medeiros, Stanford University

Brief Summary:
Open-label, non-randomized, parallel assignment, phase 2 trial assessing the safety and efficacy of distinct temozolomide treatment regimens for patients with AML and poor prognosis

Condition or disease Intervention/treatment Phase
Leukemia, Myeloid Drug: Temozolomide Phase 2

Detailed Description:

This is a single institution phase 2 clinical trial evaluating the efficacy, safety, and tolerability of tailored temozolomide therapy for patients with acute myeloid leukemia (AML) and poor risk features.

Patients will be assigned to 1 of 2 parallel treatment groups based on their AGAT promoter region methylation status, as determined by PCR.

Patients achieving a complete remission after 1 to 2 cycles of chemotherapy will be eligible to receive up to an additional 5 cycles of temozolomide of 5 or 19 days, depending on the methylation status of the AGAT promoter (consolidation phase).

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of Two Distinct Tailored Temozolomide Regimens for Patients With Acute Myeloid Leukemia Age > 60 Years and Poor Risk/Refractory Disease
Study Start Date : December 2007
Actual Primary Completion Date : December 2009
Actual Study Completion Date : January 2010

Arm Intervention/treatment
Experimental: Methylated AGAT Promoter (Group 1)
Induction: 200 mg/m2/day oral Temozolomide x 7 days
Drug: Temozolomide

Priming, Group 2 only, 100 mg/m2/day temozolomide.

Induction (both arms) 200 mg/m2/day temozolomide

Other Name: Temodar, Temodal
Experimental: Un-Methylated AGAT Promoter (Group 2)
Priming: 100 mg/m2/day oral Temozolomide x 14 days, followed by Induction: 200 mg/m2/day oral Temozolomide x 7 days
Drug: Temozolomide

Priming, Group 2 only, 100 mg/m2/day temozolomide.

Induction (both arms) 200 mg/m2/day temozolomide

Other Name: Temodar, Temodal

Primary Outcome Measures :
  1. Response Rate (CR + CRi + LFS) [ Time Frame: up to 2 months ]

    Response determined per European LeukemiaNet response criteria:

    CR = bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; absolute neutrophil count > 1.0 x 10e9/L; platelet count > 100 x 10e9/L; and independence of red cell transfusions.

    CRi = all CR criteria except for residual neutropenia (< 1.0 x 10e9/L) or thrombocytopenia (< 100 x 10e9/L)].

    Morphologic leukemia-free state (LFS) = bone marrow blasts <5%; absence of blasts with Auer rods; absence of extramedullary disease; with no hematologic recovery required.

    Relapse = bone marrow blasts >5%; reappearance of blasts in the blood; or development of extramedullary disease.

Secondary Outcome Measures :
  1. Toxicity Profile: Total Number of Drug-related Serious Adverse Events [ Time Frame: 12 months ]
  2. Toxicity Profile: Individual Subjects With Drug-related SAEs [ Time Frame: 12 months ]

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Ages Eligible for Study:   60 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients must have histologically or cytologically confirmed Acute Myeloid Leukemia, as defined by the WHO classification.
  2. Patients must be considered unfit for conventional induction chemotherapy, unwilling to receive such treatment or have evidence of disease relapse or refractory disease.
  3. For patients who have received no prior conventional chemotherapy, one of the following must be present:

    • Poor risk cytogenetics (complex abnormalities, deletions of chromosome 7 or 5, 11q23 abnormalities, inv[3])
    • Secondary leukemia (prior hematologic disorder or therapy-related leukemia).
  4. Age > 60 years of age.
  5. Life expectancy of greater than 3 months.
  6. ECOG performance status greater than 2.
  7. Patients must have normal organ and marrow function as defined below:
  8. Adequate hepatic function: Total bilirubin 1.5mg/dL, AST(SGOT)/ALT(SGPT) 2.5 X institutional upper limit of normal.
  9. Adequate renal function: serum creatinine within normal institutional limits or Calculated creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.
  10. Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  1. Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
  2. Patients may not be receiving any other investigational agents.
  3. History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or DTIC
  4. History of gastrointestinal disease or significant bowel resection that could interfere with drug absorption.
  5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  6. Prior allogeneic stem cell transplantation.
  7. Inability to swallow tablets
  8. Prior radiation up to more than 25% of bone marrow.

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 identifier (NCT number): NCT00611247

United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Bruno C. Medeiros
Principal Investigator: Bruno Carneiro de Medeiros Stanford University

Publications of Results:
Bruno C Medeiros, Holbrook E Kohrt, Richa Rajwanshi, Jason Gotlib, Steven E Coutre, Michaela Liedtke, Caroline Berube, Melody Zhang, Daniel A Arber, James L Zehnder. "Temozolomide In Acute Myeloid Leukemia: A MGMT Promoter Methylation Status-Based Treatment Stratification." Blood. 2010;116(21) (abs 3313).

Responsible Party: Bruno C. Medeiros, PI, Stanford University Identifier: NCT00611247     History of Changes
Obsolete Identifiers: NCT00426309
Other Study ID Numbers: 07815
97611 ( Other Identifier: Stanford University Alternate IRB Approval Number )
SU-12142007-936 ( Other Identifier: Stanford University )
HEMAML0004 ( Other Identifier: OnCore )
First Posted: February 8, 2008    Key Record Dates
Results First Posted: July 9, 2014
Last Update Posted: July 9, 2014
Last Verified: July 2014

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents