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Vorinostat and Low Dose Cytarabine for High Risk Myelodysplasia (GFMVOR2007)

This study has been completed.
Sponsor:
Collaborator:
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier:
NCT00776503
First received: October 20, 2008
Last updated: March 19, 2014
Last verified: November 2011
  Purpose

The purpose of this study is to determine the maximum tolerated duration and schedule of oral VORINOSTAT in addition to low dose cytarabine in the treatment of Intermediate-2 and High risk myelodysplastic syndromes.


Condition Intervention Phase
Myelodysplastic Syndromes
Drug: VORINOSTAT
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Vorinostat in Combination With Low Dose Ara-C for Patients With Intermediate-2 or High Risk Myelodysplastic Syndromes

Resource links provided by NLM:


Further study details as provided by Groupe Francophone des Myelodysplasies:

Primary Outcome Measures:
  • To determine the Maximum tolerated dose of the association [ Time Frame: After 1 cycle of treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To determine the clinical activity of this association [ Time Frame: after 3 cycles of treatment ] [ Designated as safety issue: No ]

Enrollment: 52
Study Start Date: May 2008
Study Completion Date: November 2011
Primary Completion Date: November 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: B
Cytarabine 10mg/m2 day 1-14 Vorinostat 400mg/d day 1-(7 or 10 or 14)
Drug: VORINOSTAT
vorinostat; 400mg once daily; increasing duration (7-10-14 days)
Other Names:
  • SAHA
  • ZOLINZA
Experimental: A
Cytarabine 10mg/m2 day 1-14 Vorinostat 400mg/d day 15-(21 or 24 or 28)
Drug: VORINOSTAT
vorinostat; 400mg once daily; increasing duration (7-10-14 days)
Other Names:
  • SAHA
  • ZOLINZA

Detailed Description:

This is a multi-center, open-label, non-randomized, Phase I/II study. Patients will be treated either with arm A or B dosing schedules which contain increasing durations of exposure to vorinostat. LD Ara-C will be administered once daily, subcutaneously(SC), at 10 mg/m² in Cycle 1 and escalated to 20 mg/m² daily in Cycle 2 and above for 14 out of 28 days. Oral vorinostat will be administered as 400 mg, once daily either sequentially(Arm A) or concurrently (Arm B) with LD Ara-C in Dose Level #1 for 7 days, Dose Level #2 for 10 days, or Dose Level #3 for 14 days out of each 28-day cycle. Patients who do not have disease progression and who continue to meet eligibility criteria may receive up to 3 additional 28-day cycles of treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must meet all of the following criteria to participate in the study:

    1. Patient has MDS including the following FAB sub-types: refractory anemia with blast excess (RAEB) ,transformed refractory anemia with blast excess (RAEB-t) and non proliferative Chronic MyeloMonocytic Leukemias (WBC below 13G/l).
    2. Patient has a IPSS score > 1. 5 (INT-2 and high risk categories).
    3. Patient must have been previously treated with demethylating agents (including Azacitidine and Decitabine) and :

      1. failed to respond or
      2. progress after treatment.
    4. Patient is male or female, and ≥ 18 years of age on day of signing informed consent.
    5. Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (See Appendix 6.1).
    6. Patient has recovered from toxicities due to prior therapy (less than grade 2) except for cytopenia
    7. Patient must have adequate organ function as indicated by the following laboratory values: serum creatinine <2mg/dl; total bilirubin <2,5ULN; AST<2,5ULN, ALT<2,5ULN, PAL<5ULN
    8. Patient is known to not be refractory to platelet transfusions.
    9. Female patient of childbearing potential has a negative serum pregnancy test (β-hCG) within 72 hours prior to receiving the first dose of vorinostat and or Ara-C . Female patient is not actively breastfeeding at the time of study entry.
    10. 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 becoming pregnant throughout the study, starting with Visit 1.
    11. Male patient agrees to use an adequate method of contraception for the duration of the study. Men should be advised not to father a child while receiving vorinostat and for 1 month post study.
    12. Patient is available for periodic blood sampling, study related assessments, and appropriate clinical management at the treating institution for the duration of the study.
    13. Patient has the ability to understand and willingness to sign an informed consent form indicating the investigational nature of the study.
    14. Patient is able to swallow capsules.

Exclusion Criteria:

  1. Patient had prior treatment with an HDAC inhibitor (e.g., depsipeptide or NSC-630176, MS 275, LAQ-824, 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.
  2. Patient has been previously treated with low dose (20 mg/m2 SC daily) Ara-C for MDS within 3 months of beginning this study.
  3. Patient has active and uncontrolled infection
  4. Patient has uncontrolled intercurrent illness or circumstances that could limit compliance with the study, including but not limited to the following: symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, pancreatitis, or psychiatric or social conditions that may interfere with patient compliance.
  5. 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.
  6. Patient has known human immunodeficiency virus (HIV) infection or HIV-related malignancy.
  7. Patient has clinically active hepatitis B or hepatitis C infection.
  8. Patient has a known allergy or hypersensitivity to any component of vorinostat or Ara-C.
  9. 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.
  10. Patient has received growth factors such as epoetin alfa (EPO) or granulocyte colony-stimulating factor (G-CSF) or has received non cytotoxic agents (including low dose oral chemotherapy) in the 30 days before inclusion. In case of previous cytotoxic treatment, an interval of 3 months is required.
  11. Patient is on any systemic steroids that have not been stabilized to the equivalent of ≤ 10 mg/day prednisone during the 4 weeks prior to the start of the study drugs
  12. Patients with clinical evidence of CNS leukemia.
  13. Patient has a history of GI surgery or other procedures that might interfere with the absorption or swallowing of the study drugs.
  14. Patient is unable to take and/or tolerate oral medications on a continuous basis.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00776503

Locations
France
Hôpital de la Durance
Avignon, France, 84902
Hopital Avicenne
Bobigny, France, 93009
CH René Dubos
Cergy-pontoise, France, 95303
Hematology Dpt, Hôpital Sud Francilien
Corbeil-essonnes, France, 91100
CHU Grenoble
Grenoble, France, 38043
Hôpital Edouard Heriot, dpt Hématologie Clinique
Lyon, France, 69437
Hematology Dpt, Institut Paoli Calmettes
Marseille, France, 13009
Hematology Dpt, Hopital de l'Hotel Dieu
Nantes, France, 44093
Hematology Dpt, Hopital Cochin
Paris, France, 75679
Hematology Dpt, Hopital Saint Louis
Paris, France, 75475
Centre Henri Bequerel
Rouen, France, 76038
Centre René Huguenin
Saint Cloud, France, 92210
Hematology Dpt, Hopital Haute Pierre
Strasbourg, France, 67098
Hematology Dpt, Hopital Purpan
Toulouse, France, 40031
Sponsors and Collaborators
Groupe Francophone des Myelodysplasies
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Thomas PREBET, MD Groupe Francophone des Myelodysplasies
Study Director: Norbert VEY, MD Groupe Francophone des Myelodysplasies
  More Information

No publications provided by Groupe Francophone des Myelodysplasies

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Groupe Francophone des Myelodysplasies
ClinicalTrials.gov Identifier: NCT00776503     History of Changes
Other Study ID Numbers: GFM VOR 2007-01
Study First Received: October 20, 2008
Last Updated: March 19, 2014
Health Authority: France: ANSM agence nationale de sécurité du médicament et des produits de santé

Keywords provided by Groupe Francophone des Myelodysplasies:
Epigenetic
Myelodysplasia
Cytarabine

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Pathologic Processes
Precancerous Conditions
Cytarabine
Vorinostat
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Histone Deacetylase Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014