Clinical trial NCT00611247: Phase 2 Study of Temozolomide to Treat Poor Risk / Refractory Acute Myeloid Leukemia
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Leukemia, Myeloid
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Schering-Plough
First posted: 2008-02-08
Enrollment: 42
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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 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.

Primary outcomes:
measure: Response Rate (CR + CRi + LFS)
timeFrame: up to 2 months
Secondary outcomes:
measure: Toxicity Profile: Total Number of Drug-related Serious Adverse Events
timeFrame: 12 months
measure: Toxicity Profile: Individual Subjects With Drug-related SAEs
timeFrame: 12 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
Study officials:
affiliation: Stanford University
name: Bruno Carneiro de Medeiros
role: PRINCIPAL_INVESTIGATOR
References:
citation: Medeiros BC, Kohrt HE, Gotlib J, Coutre SE, Zhang B, Arber DA, Zehnder JL. Tailored temozolomide therapy according to MGMT methylation status for elderly patients with acute myeloid leukemia. Am J Hematol. 2012 Jan;87(1):45-50. doi: 10.1002/ajh.22191. Epub 2011 Nov 4.
citation: 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).