Study of Temozolomide in Previously Untreated Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Participants With Low O6-Methylguanine Methyltransferase (MGMT) Expression (P05052 AM2) (TALL)
This study has been completed.
Sponsor:
Merck
Information provided by (Responsible Party):
Merck
ClinicalTrials.gov Identifier:
NCT00687323
First received: May 27, 2008
Last updated: January 15, 2013
Last verified: January 2013
- Full Text View
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Purpose
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.
| Condition | Intervention | Phase |
|---|---|---|
|
Leukemia, Acute Myeloid Myelodysplastic Syndrome |
Drug: temozolomide |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase II Study of Temozolomide in Previously Untreated Acute Myeloid Leukemia (AML)/Myelodysplastic Syndrome (MDS) Subjects Unsuitable for Standard Induction Therapy Exhibiting Low MGMT Expression |
Resource links provided by NLM:
Further study details as provided by Merck:
Primary Outcome Measures:
- Clinical Response at the End of Temozolomide Induction [ Time Frame: at the end of each cycle (approximately 4 weeks post start of cycle), up to a maximum 63 weeks ] [ Designated as safety issue: No ]
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.
Secondary Outcome Measures:
- Duration of Response in Participants Achieving Complete Response (CR) and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide [ Time Frame: Up to 1 year after treatment ends ] [ Designated as safety issue: No ]
- Relapse-free Survival in Participants Achieving CR and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide [ Time Frame: Up to 1 year after treatment ends ] [ Designated as safety issue: No ]
- Overall Survival in Participants Achieving CR and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide [ Time Frame: Up to 1 year after treatment ends ] [ Designated as safety issue: No ]
- Frequency of Low MGMT Expression in Previously Untreated Participants [ Time Frame: Baseline ] [ Designated as safety issue: No ]
- MGMT of Leukemic Blasts at the Time of Relapse [ Time Frame: Up to 1 year after treatment ends ] [ Designated as safety issue: No ]
- Number of Participants With CR Experiencing Clinical or Laboratory Adverse Events (AEs) [ Time Frame: From first dose to 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]
- Number of Participants With PR Experiencing Clinical or Laboratory Adverse Events (AEs) [ Time Frame: From first dose to 30 days after last dose of study drug ] [ Designated as safety issue: Yes ]
- Progression-free Survival for Participants Achieving PR Who Are on a Modified Low Dose Temozolomide Maintenance Regimen [ Time Frame: Up to 1 year after treatment ends ] [ Designated as safety issue: No ]
- Quality of Life in Participants Receiving Long Term Temozolomide Therapy [ Time Frame: From first dose to post-study visit ] [ Designated as safety issue: No ]
| Enrollment: | 47 |
| Study Start Date: | July 2007 |
| Study Completion Date: | December 2012 |
| Primary Completion Date: | May 2011 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Experimental: Temozolomide |
Drug: temozolomide
temozolomide capsules (250 mg, 100 mg, 20 mg and 5 mg), orally, once daily, at a dose of 200 mg/m^2/day for 7 days each 28-day cycle or for 5 days each 28-day cycle; or 100 mg/m^2/day for 21 days of each 28-day cycle; 12 cycles maximum.
Other Names:
|
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Criteria
Inclusion Criteria:
- 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).
Exclusion Criteria:
- 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.
Contacts and Locations
No Contacts or Locations Provided
More Information
No publications provided
| Responsible Party: | Merck |
| ClinicalTrials.gov Identifier: | NCT00687323 History of Changes |
| Other Study ID Numbers: | P05052 |
| Study First Received: | May 27, 2008 |
| Results First Received: | May 4, 2012 |
| Last Updated: | January 15, 2013 |
| Health Authority: | Canada: Health Canada |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Myeloid, Acute Leukemia, Myeloid Myelodysplastic Syndromes Preleukemia Acute Disease Neoplasms by Histologic Type Neoplasms Bone Marrow Diseases Hematologic Diseases Precancerous Conditions |
Disease Attributes Pathologic Processes Temozolomide Dacarbazine Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Pharmacologic Actions Antineoplastic Agents Therapeutic Uses |
ClinicalTrials.gov processed this record on June 18, 2013