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

NCT00611247 | Completed Phase 2 Results DMC FDA Drug

• 4 other identifiers: IRB-0781597611SU-12142007-936HEMAML0004
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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

Conditions

Leukemia, Myeloid

Outcome Measures

Primary Outcomes (1)

• Response Rate (CR + CRi + LFS)

  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.

  up to 2 months

Secondary Outcomes (2)

• Toxicity Profile: Total Number of Drug-related Serious Adverse Events

  12 months

• Toxicity Profile: Individual Subjects With Drug-related SAEs

  12 months

Study Arms (2)

Methylated AGAT Promoter (Group 1)

EXPERIMENTAL

Induction: 200 mg/m2/day oral Temozolomide x 7 days

Drug: Temozolomide

Un-Methylated AGAT Promoter (Group 2)

EXPERIMENTAL

Priming: 100 mg/m2/day oral Temozolomide x 14 days, followed by Induction: 200 mg/m2/day oral Temozolomide x 7 days

Drug: Temozolomide

Interventions

Temozolomide DRUG

Priming, Group 2 only, 100 mg/m2/day temozolomide. Induction (both arms) 200 mg/m2/day temozolomide

Also known as: Temodar, Temodal

Methylated AGAT Promoter (Group 1); Un-Methylated AGAT Promoter (Group 2)

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must have histologically or cytologically confirmed Acute Myeloid Leukemia, as defined by the WHO classification.
• Patients must be considered unfit for conventional induction chemotherapy, unwilling to receive such treatment or have evidence of disease relapse or refractory disease.
• 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).
• Age \> 60 years of age.
• Life expectancy of greater than 3 months.
• ECOG performance status greater than 2.
• Patients must have normal organ and marrow function as defined below:
• Adequate hepatic function: Total bilirubin 1.5mg/dL, AST(SGOT)/ALT(SGPT) 2.5 X institutional upper limit of normal.
• 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.
• Ability to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• 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.
• Patients may not be receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or DTIC
• History of gastrointestinal disease or significant bowel resection that could interfere with drug absorption.
• 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.
• Prior allogeneic stem cell transplantation.
• Inability to swallow tablets
• Prior radiation up to more than 25% of bone marrow.

Sponsors & Collaborators

• Bruno C. Medeiros: lead
• Schering-Plough: collaborator

Study Sites (1)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Related Publications (2)

• 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.

  PMID: 22052619 RESULT

• 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).

  RESULT

MeSH Terms

Conditions

Leukemia, Myeloid

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Bruno C Medeiros, MD
• Organization: Stanford University Medical Center

bruno.medeiros@stanford.edu

650-498-6000

Study Officials

• Bruno Carneiro de Medeiros

  Stanford University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: January 25, 2008
• First Posted: February 8, 2008
• Study Start: December 1, 2007
• Primary Completion: December 1, 2009
• Study Completion: January 1, 2010
• Last Updated: June 15, 2018
• Results First Posted: July 9, 2014

Record last verified: 2018-05

Locations

US (1)