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

Primary Purpose

Leukemia, Myeloid

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Temozolomide

About this trial

This is an interventional treatment trial for Leukemia, Myeloid

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Sites / Locations

Stanford University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Methylated AGAT Promoter (Group 1)

Un-Methylated AGAT Promoter (Group 2)

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

Toxicity Profile: Individual Subjects With Drug-related SAEs

Full Information

NCT ID

NCT00611247

First Posted

January 25, 2008

Last Updated

May 17, 2018

Sponsor

Bruno C. Medeiros

Collaborators

Schering-Plough

1. Study Identification

Unique Protocol Identification Number

NCT00611247

Brief Title

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

2. Study Status

Record Verification Date

May 2018

Overall Recruitment Status

Completed

Study Start Date

December 2007 (undefined)

Primary Completion Date

December 2009 (Actual)

Study Completion Date

January 2010 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Bruno C. Medeiros

Collaborators

Schering-Plough

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Leukemia, Myeloid

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Methylated AGAT Promoter (Group 1)

Arm Type

Experimental

Arm Description

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

Arm Title

Un-Methylated AGAT Promoter (Group 2)

Arm Type

Experimental

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Temozolomide

Other Intervention Name(s)

Temodar, Temodal

Intervention Description

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

Primary Outcome Measure Information:

Title

Response Rate (CR + CRi + LFS)

Description

Time Frame

up to 2 months

Secondary Outcome Measure Information:

Title

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

Time Frame

12 months

Title

Toxicity Profile: Individual Subjects With Drug-related SAEs

Time Frame

12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Exclusion Criteria: 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Bruno Carneiro de Medeiros

Organizational Affiliation

Stanford University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Stanford University School of Medicine

City

Stanford

State/Province

California

ZIP/Postal Code

94305

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

22052619

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.

Results Reference

result

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).

Results Reference

result

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

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