Study of Temozolomide in Previously Untreated Acute Myeloid Leukemia Patients With Low MGMT Expression (Study P05052) - Full Text View

Sponsored by:	Schering-Plough
Information provided by:	Schering-Plough
ClinicalTrials.gov Identifier:	NCT00687323

Purpose

The primary objective of this study is to evaluate the safety, tolerability, and efficacy of temozolomide in acute myeloid leukemia (AML) patients who are not candidates for standard induction therapy and exhibit low O6-methylguanine-DNA methyltransferase (MGMT) expression.

Condition	Intervention	Phase
Leukemia, Myeloid, Acute	Drug: Temozolomide	Phase II

MedlinePlus related topics: Leukemia, Adult Acute Leukemia, Adult Chronic

Drug Information available for: Temozolomide

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Open Label, Uncontrolled, Single Group Assignment, Efficacy Study
Official Title:	Phase II Study of Temozolomide in Previously Untreated Acute Myeloid Leukemia (AML) Patients Unsuitable for Standard Induction Therapy Exhibiting Low MGMT Expression

Further study details as provided by Schering-Plough:

Primary Outcome Measures:

Clinical response at the end of temozolomide induction. [ Time Frame: End of the temozolomide induction phase. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Duration of response in patients achieving complete response and proceeding to reduced dose-intensity maintenance therapy with temozolomide (200 mg/m^2/day for 5 days every 28 days). [ Time Frame: End of Study (December 2011) ] [ Designated as safety issue: No ]
Relapse-free survival and overall survival in patients achieving complete response who are maintained on a reduced dose-intensity regimen of temozolomide (200 mg/m^2/day for 5 days every 28 days). [ Time Frame: End of Study (December 2011) ] [ Designated as safety issue: No ]
Frequency of low MGMT expression in previously untreated AML patients. [ Time Frame: End of Study (December 2011) ] [ Designated as safety issue: No ]
MGMT expression in leukemic blasts at the time of relapse. [ Time Frame: End of Study (December 2011) ] [ Designated as safety issue: No ]
Safety and tolerability of a reduced dose-intensity maintenance regimen of temozolomide in patients achieving complete response. [ Time Frame: End of Study (December 2011) ] [ Designated as safety issue: Yes ]
Safety and tolerability of a modified low-dose temozolomide maintenance regimen (100 mg/m^2/day for 21 days every 28 days) in patients who achieve partial response. [ Time Frame: End of Study (December 2011) ] [ Designated as safety issue: Yes ]
Progression-free survival for a modified low-dose temozolomide maintenance regimen (100 mg/m^2/day for 21 days every 28 days) in patients who achieve partial response. [ Time Frame: End of Study (December 2011) ] [ Designated as safety issue: No ]
Quality of life of patients receiving a long-term temozolomide maintenance regimen. [ Time Frame: End of Study (December 2011) ] [ Designated as safety issue: No ]
Correlation between MGMT expression by Western blot and by direct immunohistochemistry. This will evaluate whether the latter assay could potentially serve as a useful screening tool for MGMT expression in AML. [ Time Frame: End of Study (December 2011) ] [ Designated as safety issue: No ]
Correlation between responses to temozolomide and expression of the mismatched repair gene MLH1. This will evaluate whether this gene may be a mediator of drug resistance to temozolomide in low MGMT-expressing AML. [ Time Frame: End of Study (December 2011) ] [ Designated as safety issue: No ]

Estimated Enrollment:	44
Study Start Date:	July 2007
Estimated Study Completion Date:	June 2010
Estimated Primary Completion Date:	June 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Single Arm: Experimental It is the only arm of the study. All subjects will receive an initial induction cycle of temozolomide. Treatment will then continue unchanged, vary, or end for each subject depending on the subject's clinical response to the initial induction cycle.	Drug: Temozolomide All subjects will receive 1 initial induction cycle of temozolomide and clinical response will be evaluated after. Subjects who achieve complete response (CR) will receive 1 cycle of consolidation therapy, followed by a reduced dose-intensity maintenance regimen for a max of 12 cycles. Subjects who achieve partial response (PR) will receive a 2nd induction cycle. Those who achieve CR will receive 1 cycle of consolidation therapy followed by the reduced dose-intensity maintenance regimen for a max of 12 cycles. Subjects who don't achieve CR after the 2nd induction will receive temozolomide at 100 mg/m^2/day for 21 days every 28 days until disease progression. Subjects who don't achieve CR or PR with 1 cycle of induction therapy will be classified as no response and withdrawn from study. Subjects who achieve CR or PR and then show evidence of disease progression will also be withdrawn from study. Caps containing 5 mg, 20 mg, 100 mg, or 200 mg of temozolomide will be used in this study.

Arms

Assigned Interventions

Single Arm: Experimental

It is the only arm of the study. All subjects will receive an initial induction cycle of temozolomide. Treatment will then continue unchanged, vary, or end for each subject depending on the subject's clinical response to the initial induction cycle.

Drug: Temozolomide

All subjects will receive 1 initial induction cycle of temozolomide and clinical response will be evaluated after. Subjects who achieve complete response (CR) will receive 1 cycle of consolidation therapy, followed by a reduced dose-intensity maintenance regimen for a max of 12 cycles. Subjects who achieve partial response (PR) will receive a 2nd induction cycle. Those who achieve CR will receive 1 cycle of consolidation therapy followed by the reduced dose-intensity maintenance regimen for a max of 12 cycles. Subjects who don't achieve CR after the 2nd induction will receive temozolomide at 100 mg/m^2/day for 21 days every 28 days until disease progression. Subjects who don't achieve CR or PR with 1 cycle of induction therapy will be classified as no response and withdrawn from study. Subjects who achieve CR or PR and then show evidence of disease progression will also be withdrawn from study. Caps containing 5 mg, 20 mg, 100 mg, or 200 mg of temozolomide will be used in this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Only the patients who meet all these criteria can be enrolled in the study:

Adult patients >18 years.
Confirmed diagnosis of acute myeloid leukemia (AML) or any subtype except acute promyelocytic leukemia (APL), by the World Health Organization (WHO) criteria.
No prior AML chemotherapy except hydroxyurea.
Leukemic blast count <30x10^9/L at the start of therapy. Prior cytoreduction with hydroxyurea (maximum 1 week) is permitted.
Patient is not a candidate for aggressive induction chemotherapy based on at least one of the following:
- adverse-risk cytogenetics (complete or partial deletion of chromosome 5 or 7, complex [>3] cytogenetic abnormalities, inv3, 11q23 abnormalities);
- secondary AML (antecedent hematologic disorder or therapy-related AML);
- comorbid medical illnesses precluding standard induction therapy;
- patient's refusal of standard induction therapy.
Confirmed low MGMT expression (MGMT: beta-actin <0.2), as evaluated by Western blot.
ECOG performance status of 0, 1, or 2.
Patients must sign a study-specific informed consent form.
Use of medically approved contraception in fertile males and females.
Negative urine or serum pregnancy test for women of childbearing potential (72 hours prior to Baseline).

Exclusion Criteria:

Patients will not be enrolled if any of the following criteria apply:

Serum bilirubin >2 times the upper limit of normal (ULN), or serum aspartate aminotransferase / alanine aminotransferase >5 times ULN.
Serum creatinine >200 umol/L.
History of other malignancies within 1 year prior to study entry, with the exception of localized nonmelanomatous skin cancer or cervical cancer in situ.
Presence of active uncontrolled infection.
Known HIV infection.
Any medical condition that may interfere with protocol evaluation or oral medication intake.
Prior chemotherapy other than hydroxyurea.
History of noncompliance with other therapies.
Any condition that may potentially hamper compliance with study protocol and follow-up schedule.
Any patient who is not a suitable candidate for temozolomide according to the clinician's best judgment.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00687323

Contacts

Contact: SP Clinical Trial Registry Call Center

1-888-772-8734

Locations

Canada
Investigational Site 4	Recruiting
Montreal, Canada, H1T2M4

Sponsors and Collaborators

Schering-Plough

More Information

Responsible Party:	Schering-Plough ( Head, Clinical Trials Registry & Results Disclosure Group )
Study ID Numbers:	P05052
Study First Received:	May 27, 2008
Last Updated:	January 14, 2009
ClinicalTrials.gov Identifier:	NCT00687323
Health Authority:	Canada: Health Canada

Study placed in the following topic categories:

Leukemia
Acute myelogenous leukemia
Leukemia, Myeloid

Leukemia, Myeloid, Acute
Temozolomide
Acute myelocytic leukemia

Additional relevant MeSH terms:

Neoplasms
Neoplasms by Histologic Type
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009