Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00687323
Other study ID # P05052
Secondary ID MK-7365-240
Status Completed
Phase Phase 2
First received May 27, 2008
Last updated February 12, 2015
Start date July 2007
Est. completion date December 2012

Study information

Verified date February 2015
Source Merck Sharp & Dohme Corp.
Contact n/a
Is FDA regulated No
Health authority Canada: Health Canada
Study type Interventional

Clinical Trial 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.


Recruitment information / eligibility

Status Completed
Enrollment 47
Est. completion date December 2012
Est. primary completion date May 2011
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility 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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Intervention

Drug:
temozolomide


Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Merck Sharp & Dohme Corp.

References & 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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary 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 No
Secondary Duration of Response in Participants Achieving Complete Response (CR) and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide 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. Up to 1 year after treatment ends (up to 115 weeks) No
Secondary Relapse-free Survival in Participants Achieving CR or CRp and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide Relapse-free survival was defined as time to disease progression. 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. Start of treatment until disease progression [up to 1 year after treatment ends (up to 115 weeks)] No
Secondary Overall Survival (OS) in Participants Achieving CR or CRp and Proceeding to Reduced Dose-intensity Maintenance Therapy With Temozolomide OS was defined as the time from start of treatment until death or end of study.
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.
Start of treatment until death or end of study [up to 1 year after treatment ends (up to 115 weeks)] No
Secondary Number of Previously Untreated Participants With Low O6-Methylguanine Methyltransferase (MGMT) Expression Low MGMT expression was defined as MGMT/ß-actin ratio < 0.2. MGMT & ß-actin are cancer biomarkers. Baseline No
Secondary MGMT Expression in Leukemic Blasts at the Time of Relapse Low MGMT expression was defined as MGMT/ß-actin ratio of <0.2.
MGMT & ß-actin are cancer biomarkers.
Up to 1 year after treatment ends (up to 115 weeks) No
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 Toxicity was defined as any adverse event experienced by a participant regardless of causal relationship with study treatment. An adverse event (AE) was defined as any untoward medical occurrence in a participant administered a pharmaceutical product, biologic (at any dose), or medical device, which did not necessarily have a causal relationship with the treatment. Adverse events may have included the onset of new illness and/or the exacerbation of preexisting conditions. From first dose to 30 days after last dose of study drug (up to 67 weeks) Yes
Secondary Progression-free Survival for Participants Achieving PR, MLSF, or MR Progression-free survival was defined as time to disease progression. 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. Start of treatment until disease progression [up to 1 year after treatment ends (up to 115 weeks)] No
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 The EORTC QLQ-C30 was a 30-item questionnaire developed to assess the QoL of cancer patients. Scores ranged from 0 -100. For functional and global QoL scales, higher scores meant a better level of function. For symptom-oriented scales, a higher score meant more severe symptoms and a decrease in QoL. Baseline and post-study visit (63 weeks) No
Secondary Quality of Life (QoL) in Participants Receiving Long Term Temozolomide Therapy Assessed by EORTC QLQ-LC13 The EORTC QLQ-LC13 was a 13-item questionnaire developed to supplement the EORTC QLQ-C30 in lung cancer patients. It had a score range 0-100 with higher scores representing an increase in symptoms. Baseline and post-study visit (63 weeks) No
Secondary Quality of Life (QoL) in Participants Receiving Long Term Temozolomide Therapy Assessed by Functional Assessment of Cancer Therapy (FACT)-G The FACT-G was a 27-item questionnaire developed to assess the QoL in patients with chronic illnesses. Scores ranged from 0 to 28. For physical well being, lower scores indicated a better outcome. For functional well being, higher scores indicated a better outcome. For social & emotional well being, whether a high score or a lower one indicated a better outcome depended on the question. Baseline and post-study visit (63 weeks) No
See also
  Status Clinical Trial Phase
Completed NCT04022785 - PLX51107 and Azacitidine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndrome Phase 1
Completed NCT01200355 - Posaconazole Versus Micafungin for Prophylaxis Against Invasive Fungal Infections During Neutropenia in Patients Undergoing Chemotherapy for Acute Myelogenous Leukemia, Acute Lymphocytic Leukemia or Myelodysplastic Syndrome Phase 4
Active, not recruiting NCT02530463 - Nivolumab and/or Ipilimumab With or Without Azacitidine in Treating Patients With Myelodysplastic Syndrome Phase 2
Completed NCT02057185 - Occupational Status and Hematological Disease
Completed NCT01682226 - Cord Blood With T-Cell Depleted Haplo-identical Peripheral Blood Stem Cell Transplantation for Hematological Malignancies Phase 2
Completed NCT02485535 - Selinexor in Treating Patients With Intermediate- and High-Risk Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome After Transplant Phase 1
Completed NCT03941769 - 2018-0674 - IL-7 for T-Cell Recovery Post Haplo and CB Transplant - Phase I/II Phase 1/Phase 2
Completed NCT00001637 - Immunosuppressive Preparation Followed by Blood Cell Transplant for the Treatment of Blood Cancers in Older Adults Phase 2
Recruiting NCT06195891 - Orca-T Following Chemotherapy and Total Marrow and Lymphoid Irradiation for the Treatment of Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia or Myelodysplastic Syndrome Phase 1
Active, not recruiting NCT04188678 - Resiliency in Older Adults Undergoing Bone Marrow Transplant N/A
Completed NCT00987480 - Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine Phase 2
Recruiting NCT02356159 - Study of Palifermin (Kepivance) in Persons Undergoing Unrelated Donor Allogeneic Hematopoietic Cell Transplantation Phase 1/Phase 2
Completed NCT04666025 - SARS-CoV-2 Donor-Recipient Immunity Transfer
Completed NCT02756572 - Early Allogeneic Hematopoietic Cell Transplantation in Treating Patients With Relapsed or Refractory High-Grade Myeloid Neoplasms Phase 2
Terminated NCT02877082 - Tacrolimus, Bortezomib, & Thymoglobulin in Preventing Low Toxicity GVHD in Donor Blood Stem Cell Transplant Patients Phase 2
Completed NCT02543879 - Study of a Novel BET Inhibitor FT-1101 in Patients With Relapsed or Refractory Hematologic Malignancies Phase 1
Completed NCT02188290 - Transplant-Related Mortality in Patients Undergoing a Peripheral Blood Stem Cell Transplantation or an Umbilical Cord Blood Transplantation N/A
Completed NCT02262312 - Iron Overload and Transient Elastography in Patients With Myelodysplastic Syndrome Phase 0
Recruiting NCT02330692 - Cohort Study of New Prognostic Factors With Peripheral Blood and Bone Marrow Evaluation at the Time of Diagnosis and Relapse in Myelodysplastic Syndrome
Completed NCT01684150 - A Phase 1, Open-Label, Dose-Escalation & Expanded Cohort, Continuous IV Infusion, Multi-center Study of the Safety, Tolerability,PK & PD of EPZ-5676 in Treatment Relapsed/Refractory Patients With Leukemias Involving Phase 1