Study of Temozolomide in Previously Untreated Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Participants With Low O6-Methylguanine Methyltransferase (MGMT) Expression (P05052)

NCT00687323 | Completed Phase 2 Results DMC

• 2 other identifiers: P05052MK-7365-240
• Study Type: interventional
• Target: 47
• Locations: 0 countries
• Sites: N/A

Brief Summary

The primary objective of this study is to evaluate the safety, tolerability, and efficacy of temozolomide in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) participants who are not candidates for standard induction therapy and exhibit low MGMT expression.

Conditions

Leukemia, Acute Myeloid; Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Clinical Response at the End of Temozolomide Induction

  Complete Response (CR): \< 5% blasts in normocellular bone marrow (BM); Absolute Neutrophil Count (ANC) \> 1.0 x 10\^9/L, platelets \> 100 x 10\^9/L, and no extramedullary disease. CR with incomplete platelet recovery (CRp): All the criteria of CR but with platelets \< 100 x 10\^9/L but ≥ 50 x 10\^9/L and platelet transfusion independent. Morphologic leukemia-free state (MLFS): complete clearance of blasts from marrow and blood, but criteria for CR or CRp not met. Partial response (PR): decrease ≥ 50% BM blasts. Minimal Response (MR): decrease ≥ 25% but \<50% BM blasts.

  at the end of each cycle (approximately 4 weeks post start of cycle), up to a maximum 63 weeks

Secondary Outcomes (10)

• Duration of Response in Participants Achieving Complete Response (CR) and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide

  Up to 1 year after treatment ends (up to 115 weeks)

• Relapse-free Survival in Participants Achieving CR or CRp and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide

  Start of treatment until disease progression [up to 1 year after treatment ends (up to 115 weeks)]

• Overall Survival (OS) in Participants Achieving CR or CRp and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide

  Start of treatment until death or end of study [up to 1 year after treatment ends (up to 115 weeks)]

• Number of Previously Untreated Participants With Low O6-Methylguanine Methyltransferase (MGMT) Expression

  Baseline

• MGMT Expression in Leukemic Blasts at the Time of Relapse

  Up to 1 year after treatment ends (up to 115 weeks)

Study Arms (1)

Temozolomide

EXPERIMENTAL

Temozolomide capsules orally, once daily: 1 induction cycle (200 mg/m\^2/day for 7 days in 1 28 day cycle), 1 consolidation cycle (200 mg/m\^2/day for 7 days in 1 28 day cycle), then 200 mg/m\^2/day for 7 days each 28-day cycle or for 5 days each 28-day cycle (12 cycle maximum). Alternatively participants could have received 100 mg/m\^2/day for 21 days of each 28-day cycle (12 cycle maximum).

Drug: temozolomide

Interventions

temozolomide DRUG

Also known as: Temodol, SCH 052365, MK-7365

Temozolomide

Eligibility Criteria

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

You may qualify if:

• Confirmed diagnosis of acute myeloid leukemia (AML), any subtype except acute promyelocytic leukemia (APL), by the World Health Organization (WHO) criteria, or high risk MDS with blasts between 10 and 20% in the bone marrow.
• No prior AML chemotherapy except hydroxyurea.
• Leukemic blast count \<30x10\^9/L at the start of therapy. Prior cytoreduction with hydroxyurea (maximum 14 days) is permitted.
• Participant is not a candidate for aggressive induction based on at least one of the following: adverse-risk cytogenetics (complete or partial deletion of 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; participant's refusal of standard induction therapy.
• Confirmed low MGMT expression (MGMT: beta-actin ≤0.2), as evaluated by Western blot, or weak MGMT expression defined as \> 0.2 and ≤2.5 if promoter is methylated, upon Sponsor approval.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
• 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).

You may not qualify if:

• 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 human immunodeficiency virus (HIV) infection.
• Any medical condition that may interfere with protocol evaluation or oral medication intake.
• Prior chemotherapy other than hydroxyurea.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Related Publications (1)

• Brandwein JM, Yang L, Schimmer AD, Schuh AC, Gupta V, Wells RA, Alibhai SM, Xu W, Minden MD. A phase II study of temozolomide therapy for poor-risk patients aged >or=60 years with acute myeloid leukemia: low levels of MGMT predict for response. Leukemia. 2007 Apr;21(4):821-4. doi: 10.1038/sj.leu.2404545. Epub 2007 Jan 25. No abstract available.

  PMID: 17252015 RESULT

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Myelodysplastic Syndromes

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 27, 2008
• First Posted: May 30, 2008
• Study Start: July 30, 2007
• Primary Completion: May 9, 2011
• Study Completion: December 23, 2012
• Last Updated: June 7, 2017
• Results First Posted: July 18, 2012

Record last verified: 2017-05

Data Sharing

• IPD Sharing: Will share