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Phase 2 Temozolomide Plus Vorinostat in Relapse/Refractory Acute Myeloid Leukemia (AML)

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ClinicalTrials.gov Identifier: NCT01550224
Recruitment Status : Completed
First Posted : March 9, 2012
Last Update Posted : May 21, 2018
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Bruno C. Medeiros, Stanford University

Brief Summary:
The purpose of the study is to first determine if temozolomide plus vorinostat in combination can control relapsed or refractory acute myeloid leukemia (AML) and determine if this combination can be safely taken. The study will look at the side effects of the Temozolomide plus Vorinostat in combination and whether the treatment schedule is tolerated.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia With 11q23-abnormality in Relapse Drug: Temozolomide Drug: Vorinostat Phase 2

Detailed Description:
The primary endpoint of the study is to determine the clinical efficacy as determined by the rate of morphological complete remission, of 2 different treatment regimens of temozolomide and vorinostat administered to 2 distinct groups of participants patients with AML and poor prognostic features. Participants will be allocated to treatment on the basis of O6-methylguanine DNA methyltransferase (MGMT) promoter methylation status.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 23 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 2 Study of Temozolomide Plus Vorinostat in Patients With Relapse/Refractory Acute Myeloid Leukemia (AML)
Actual Study Start Date : May 1, 2013
Actual Primary Completion Date : November 17, 2014
Actual Study Completion Date : November 17, 2014


Arm Intervention/treatment
Active Comparator: Group 1 - Methylated MGMT promoter
Participants with methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have no expression of MGMT protein, will be assigned into Group 1, and will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Drug: Temozolomide

An alkylating agent administered:

Group 2: 100 mg/m²/day for 14 days Both groups: 200 mg/m²/day for 7days

Other Names:
  • Temodar
  • Temodal
  • Temcad
  • TMZ

Drug: Vorinostat
A synthetic hydroxamic acid derivative with antineoplastic activity administered at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
Other Name: Zolinza

Active Comparator: Group 2 - Non-Methylated MGMT promoter
Participants with non-methylated O6-methylguanine DNA methyltransferase (MGMT) promoter, ie, expected to have expression MGMT protein, will be assigned to into Group 2, and will initially receive daily, low doses (protracted dose schedule) of temozolomide (100 mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, participants will receive vorinostat 500 mg orally 3 times daily for 3 days, followed by conventional doses of temozolomide (200 mg/m2 for 7 days).
Drug: Temozolomide

An alkylating agent administered:

Group 2: 100 mg/m²/day for 14 days Both groups: 200 mg/m²/day for 7days

Other Names:
  • Temodar
  • Temodal
  • Temcad
  • TMZ

Drug: Vorinostat
A synthetic hydroxamic acid derivative with antineoplastic activity administered at 500 mg orally 3 times daily for 3 days prior to Temozolomide 200 mg/m²/day.
Other Name: Zolinza




Primary Outcome Measures :
  1. Complete Remission [ Time Frame: 36 months ]
    This study evaluates the clinical efficacy of temozolomide + vorinostat, as assessed by the rate of morphological complete remission (mCR) at 36 months. mCR is defined as the morphologic leukemia-free state (< 5% blasts in bone marrow sample that has marrow spicules; ≥ 200 nucleated cells; no blasts with Auer rods; no persistence of extramedullary disease) plus absolute neutrophil count (ANC) > 1,000/µL and platelets ≥ 100,000/µL.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01550224


Locations
United States, California
Stanford University Medical Center
Stanford, California, United States, 94305
Sponsors and Collaborators
Stanford University
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Bruno Carneiro de Medeiros, MD Stanford University

Responsible Party: Bruno C. Medeiros, Associate Professor of Medicine (Hematology), Stanford University
ClinicalTrials.gov Identifier: NCT01550224     History of Changes
Other Study ID Numbers: IRB-22794
HEMAML0017 ( Other Identifier: OnCore )
First Posted: March 9, 2012    Key Record Dates
Last Update Posted: May 21, 2018
Last Verified: May 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Recurrence
Neoplasms by Histologic Type
Neoplasms
Disease Attributes
Pathologic Processes
Temozolomide
Dacarbazine
Vorinostat
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Histone Deacetylase Inhibitors
Enzyme Inhibitors