Phase 2
N=195
Study of Temozolomide in Previously Untreated Acute Myeloid Leukemia (AML) and Myelodysplastic Syndrome (MDS) Participants With Low O6-Methylguanine Methyltransferase (MGMT) Expression (P05052)
Leukemia, Acute Myeloid · Myelodysplastic Syndrome
Bottom Line
View on ClinicalTrials.gov: NCT00687323 ↗Enrolled (actual)
195
Serious AEs
53.2%
Results posted
Jul 2012
Primary outcome: Primary: Clinical Response at the End of Temozolomide Induction — 10; 2; 4; 8 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- temozolomide (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Merck Sharp & Dohme LLC
- Primary completion
- May 2011
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Clinical Response at the End of Temozolomide Induction |
10; 2; 4; 8; 7 | — |
| SECONDARY Duration of Response in Participants Achieving Complete Response (CR) and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide |
408 | — |
| SECONDARY Relapse-free Survival in Participants Achieving CR or CRp and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide |
10.5 | — |
| SECONDARY Overall Survival (OS) in Participants Achieving CR or CRp and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide |
21.4 | — |
| SECONDARY Number of Previously Untreated Participants With Low O6-Methylguanine Methyltransferase (MGMT) Expression |
81 | — |
| SECONDARY MGMT Expression in Leukemic Blasts at the Time of Relapse |
— | — |
| SECONDARY Number of Participants With CR, PR, or MLFS Who Received Modified Low Dose Maintenance Therapy (100 mg/m^2/Day x21 Days of Each 28 Day Cycle) and Experienced Toxicity |
1 | — |
| SECONDARY Progression-free Survival for Participants Achieving PR, MLSF, or MR |
1.6 | — |
| SECONDARY Quality of Life (QoL) in Participants Receiving Long Term Temozolomide Therapy Assessed by European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-30 |
— | — |
| SECONDARY Quality of Life (QoL) in Participants Receiving Long Term Temozolomide Therapy Assessed by EORTC QLQ-LC13 |
— | — |
| SECONDARY Quality of Life (QoL) in Participants Receiving Long Term Temozolomide Therapy Assessed by Functional Assessment of Cancer Therapy (FACT)-G |
— | — |
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.
Eligibility 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 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.
Data sourced from ClinicalTrials.gov (NCT00687323). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.