Clinical trial · Interventional

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

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

NCT00687323CI-TRIAL-00028016TALLcompletedPhase 2Results postedClinicalTrials.gov clinicaltrialsPublishedExplore in graph →

Summary

Brief summary (as posted)

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

Conditions (2)

Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.

Condition (as posted)	Mapped entity	Match	Confidence
Leukemia, Acute Myeloid	Acute Myeloid Leukemia	CURATED_BROADER	0.80
Myelodysplastic Syndrome	Myelodysplastic Syndrome	CURATED_BROADER	0.80

Interventions

Interventions (1)

Intervention	Type	Mapped drug	Match
temozolomide	Drug	Temozolomide	ALIAS

Design

Arms and outcomes

Arms (1)

type
EXPERIMENTAL
label
Temozolomide
description
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).
interventionNames
1. Drug: temozolomide

Primary outcomes (1)

measure
Clinical Response at the End of Temozolomide Induction
timeFrame
at the end of each cycle (approximately 4 weeks post start of cycle), up to a maximum 63 weeks
description
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.

Eligibility

Eligibility (as posted)

Sex: All
Minimum age: 18 Years

Show eligibility criteria text

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.

References

Publications (1)

RESULTBrandwein 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