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Phase II Temozolomide + Vorinostat in Patients (>60) w/ Newly Diagnosed or Relapse/Refractory AML

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by Stanford University
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Stanford University
ClinicalTrials.gov Identifier:
NCT01550224
First received: March 7, 2012
Last updated: August 11, 2014
Last verified: August 2014

March 7, 2012
August 11, 2014
May 2013
April 2015   (final data collection date for primary outcome measure)
Rate of morphological complete remission [ Time Frame: 36 months ] [ Designated as safety issue: Yes ]
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 in patients with AML and poor prognostic features.
Same as current
Complete list of historical versions of study NCT01550224 on ClinicalTrials.gov Archive Site
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Phase II Temozolomide + Vorinostat in Patients (>60) w/ Newly Diagnosed or Relapse/Refractory AML
A Phase 2 Study of Temozolomide Plus Vorinostat for Elderly Patients (>60) With Newly Diagnosed Acute Myeloid Leukemia (AML) or Relapse/Refractory AML

The purpose of the study is to first determine if Temozolomide plus Vorinostat in combination can control relapsed or refractory 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.

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 in patients with AML and poor prognostic features.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Acute Myeloid Leukemia With 11q23-abnormality in Relapse
Drug: Temozolomide
100-200 mg/m2/d oral
Other Names:
  • Temodar
  • Temodal
  • Active Comparator: GROUP 1 (Methylated MGMT)
    Patients with methylated MGMT promoter (expected to have no expression of MGMT protein expected) will be stratified into group 1 and will be treated with conventional doses of temozolomide (200mg/m2 for 7 days).
    Intervention: Drug: Temozolomide
  • Active Comparator: GROUP 2 (Non-Methylated MGMT)
    2. Patients where the MGMT promoter is not methylated (expected to have expression MGMT protein expected) will be stratified into group 2. These patients will initially receive daily, low doses (protracted dose schedule) of temozolomide (100mg/m2) for 14 days in an attempt to inactivate MGMT activity. Following the protracted dose schedule, patients will be submitted to a repeat bone marrow biopsy to assess the status of the disease and the effects of low dose temozolomide in acute leukemia blasts, and following three days of vorinostat therapy will receive conventional doses of temozolomide for another 7 days.
    Intervention: Drug: Temozolomide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
45
April 2016
April 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Female patient of childbearing potential has a negative serum pregnancy test beta-hCG within 72 hours prior to receiving the first dose of vorinostat.
  • Female patient is either post menopausal, free from menses for > 2 years, surgically sterilized or willing to use 2 adequate barrier methods of contraception to prevent pregnancy or agrees to abstain from heterosexual activity throughout the study, starting with Visit 1.
  • Male patient agrees to use an adequate method of contraception for the duration of the study and 1 month following coming off study or of study completion.
  • Patient, or the patient's legal representative, has voluntarily agreed to participate by giving written informed consent.
  • Patient is >=18 years of age on day of signing informed consent.
  • Patient is available for periodic blood sampling, study related assessments, and management at the treating institution for the duration of the study.

Exclusion Criteria:

  • Patient who has had chemotherapy, radiotherapy, or biological therapy within 30 days (42 days for nitrosoureas or mitomycin C) prior to initial dosing with study drug(s)or who has not recovered from adverse events due to agents administered more than 30 days earlier, except for hydroxyurea.
  • Patient is currently participating or has participated in a study with an investigational compound or device within 30 days of initial dosing with study drug(s).
  • Patient had prior treatment within the past 30 days with an HDAC inhibitor (e.g., romidepsin (Depsipeptide), NSC-630176, MS 275, LAQ-824, belinostat (PXD-101), LBH589, MGCD0103, CRA024781, etc). Patients who have received compounds with HDAC inhibitor-like activity, such as valproic acid, as anti-tumor therapy should not enroll in this study. Patients who have received such compounds for other indications, e.g. valproic acid for epilepsy, may enroll after a 30-day washout period.
  • Patients may not be receiving any other investigational agents.
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to temozolomide or DTIC or vorinostat.
  • History of gastrointestinal disease or significant bowel resection that could interfere with drug absorption.
  • Uncontrolled intercurrent illness (as defined by the investigators) including, but not limited to, ongoing or active infection (HIV, Hepatitis B or Hepatitis C), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Prior allogeneic stem cell transplantation within 2 months of trial enrollment.

Inability to swallow tablets.

  • Prior radiation up to more than 25% of bone marrow.
  • Pregnancy or lactation (2 negative pregnancy test and two methods of contraception of abstinence required).
  • Prior HDAC inhibitor within 30 days of initiating trial therapy as listed above. Concomitant radiotherapy, chemotherapy, or immunotherapy.

Exclusion Criteria Based on Medical History or Current Medical Status

- Patient has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

Patient is, at the time of signing informed consent, a regular user (including "recreational use") of any illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse.

Patient is pregnant or breast feeding, or expecting to conceive or father children within the projected duration of the study.

Patient with a "currently active" second malignancy, other than nonmelanoma skin cancer and carcinoma in situ of the cervix, should not be enrolled. Patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy, are disease free from prior malignancies for >5 years or are considered by their physician to be at less than 30% risk of relapse.

- Patient has an active infection or has received intravenous antibiotics, antiviral, or antifungal agents within 2 weeks prior to the start of the study drug.

Patient has uncontrolled intercurrent illness or circumstances that could limit compliance with the study, including, but not limited to the following: active infection, acute or chronic graft versus host disease, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric conditions.

Patient has a history or current evidence of any condition, therapy, or lab abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study or is not in the best interest of the patient to participate.

Patient has a history of a gastrointestinal surgery or other procedures that might, in the opinion of the investigator, interfere with the absorption or swallowing of the study drugs.

Both
18 Years and older
No
United States
 
NCT01550224
HEMAML0017, HEMAML0017, 22794
Yes
Stanford University
Stanford University
Merck Sharp & Dohme Corp.
Principal Investigator: Bruno Carneiro de Medeiros, MD Stanford University
Stanford University
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP