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

This study has been completed.
Sponsor:
Collaborator:
Schering-Plough
Information provided by (Responsible Party):
Bruno C. Medeiros, Stanford University
ClinicalTrials.gov Identifier:
NCT00611247
First received: January 25, 2008
Last updated: March 16, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Leukemia, Myeloid
Drug: Temozolomide
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Response rate (CR + CRp + LFS) [ Time Frame: 2 months ] [ Designated as safety issue: No ]
    CR = complete remission CRp = complete remission with incomplete count recovery LFS = leukemia-free state


Secondary Outcome Measures:
  • To determine the toxicity profile of these treatment regimens in this patient population [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]
  • To determine whether temozolomide treatment regimens, in this patient population, can be tailored according to the methylation status of the promoter region of the AGAT gene [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]
  • To determine whether temozolomide, when given in protracted doses, can sensitize leukemic blasts with non-methylated AGAT promoter to temozolomide [ Time Frame: 2 months ] [ Designated as safety issue: Yes ]

Enrollment: 42
Study Start Date: December 2007
Study Completion Date: January 2010
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Methylated AGAT Promoter (Group 1)
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)
100 mg/m2/day oral Temozolomide x 14 days followed by 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

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).

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00611247

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
Sponsors and Collaborators
Bruno C. Medeiros
Schering-Plough
Investigators
Principal Investigator: Bruno Carneiro de Medeiros Stanford University
  More Information

Publications:
Responsible Party: Bruno C. Medeiros, PI, Stanford University
ClinicalTrials.gov Identifier: NCT00611247     History of Changes
Obsolete Identifiers: NCT00426309
Other Study ID Numbers: 07815, 97611, SU-12142007-936, HEMAML0004
Study First Received: January 25, 2008
Last Updated: March 16, 2014
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Neoplasms by Histologic Type
Neoplasms
Temozolomide
Dacarbazine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 23, 2014