Vorinostat and Low Dose Cytarabine for High Risk Myelodysplasia

NCT00776503 | Completed Phase 1 DMC

• 1 other identifier: GFM VOR 2007-01
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 14

Brief Summary

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.

Conditions

Myelodysplastic Syndromes

Keywords

Epigenetic; Myelodysplasia; Cytarabine

Outcome Measures

Primary Outcomes (1)

• To determine the Maximum tolerated dose of the association

  After 1 cycle of treatment

Secondary Outcomes (1)

• To determine the clinical activity of this association

  after 3 cycles of treatment

Study Arms (2)

B

EXPERIMENTAL

Cytarabine 10mg/m2 day 1-14 Vorinostat 400mg/d day 1-(7 or 10 or 14)

Drug: VORINOSTAT

A

EXPERIMENTAL

Cytarabine 10mg/m2 day 1-14 Vorinostat 400mg/d day 15-(21 or 24 or 28)

Drug: VORINOSTAT

Interventions

VORINOSTAT DRUG

vorinostat; 400mg once daily; increasing duration (7-10-14 days)

Also known as: SAHA, ZOLINZA

A; B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all of the following criteria to participate in the study:
• 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).
• Patient has a IPSS score \> 1. 5 (INT-2 and high risk categories).
• Patient must have been previously treated with demethylating agents (including Azacitidine and Decitabine) and :
• failed to respond or
• progress after treatment.
• Patient is male or female, and ≥ 18 years of age on day of signing informed consent.
• Patient has an Eastern Cooperative Oncology Group (ECOG) performance status ≤2 (See Appendix 6.1).
• Patient has recovered from toxicities due to prior therapy (less than grade 2) except for cytopenia
• 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
• Patient is known to not be refractory to platelet transfusions.
• 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.
• 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.
• 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.
• Patient is available for periodic blood sampling, study related assessments, and appropriate clinical management at the treating institution for the duration of the study.

You may not qualify if:

• 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.
• Patient has been previously treated with low dose (20 mg/m2 SC daily) Ara-C for MDS within 3 months of beginning this study.
• Patient has active and uncontrolled infection
• 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.
• 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.
• Patient has known human immunodeficiency virus (HIV) infection or HIV-related malignancy.
• Patient has clinically active hepatitis B or hepatitis C infection.
• Patient has a known allergy or hypersensitivity to any component of vorinostat or Ara-C.
• 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 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
• Patients with clinical evidence of CNS leukemia.
• Patient has a history of GI surgery or other procedures that might interfere with the absorption or swallowing of the study drugs.
• Patient is unable to take and/or tolerate oral medications on a continuous basis.

Sponsors & Collaborators

• Groupe Francophone des Myelodysplasies: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (14)

Hôpital de la Durance

Avignon, 84902, France

Location

Hopital Avicenne

Bobigny, 93009, France

Location

CH René Dubos

Cergy-Pontoise, 95303, France

Location

Hematology Dpt, Hôpital Sud Francilien

Corbeil-Essonnes, 91100, France

Location

CHU Grenoble

Grenoble, 38043, France

Location

Hôpital Edouard Heriot, dpt Hématologie Clinique

Lyon, 69437, France

Location

Hematology Dpt, Institut Paoli Calmettes

Marseille, 13009, France

Location

Hematology Dpt, Hopital de l'Hotel Dieu

Nantes, 44093, France

Location

Hematology Dpt, Hopital Saint Louis

Paris, 75475, France

Location

Hematology Dpt, Hopital Cochin

Paris, 75679, France

Location

Centre Henri Bequerel

Rouen, 76038, France

Location

Centre René Huguenin

Saint-Cloud, 92210, France

Location

Hematology Dpt, Hopital Haute Pierre

Strasbourg, 67098, France

Location

Hematology Dpt, Hopital Purpan

Toulouse, 40031, France

Location

Related Publications (1)

• Prebet T, Braun T, Beyne-Rauzy O, Dreyfus F, Stammatoullas A, Wattel E, Ame S, Raffoux E, Delaunay J, Charbonnier A, Ades L, Fenaux P, Vey N. Combination of vorinostat and low dose cytarabine for patients with azacitidine-refractory/relapsed high risk myelodysplastic syndromes. Leuk Res. 2014 Jan;38(1):29-33. doi: 10.1016/j.leukres.2013.07.023. Epub 2013 Aug 13.

  PMID: 23953882 DERIVED

MeSH Terms

Conditions

Myelodysplastic Syndromes; Anemia, Refractory, with Excess of Blasts

Interventions

Vorinostat

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Anemia, Refractory; Anemia

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Study Officials

• Thomas PREBET, MD

  Groupe Francophone des Myelodysplasies

  PRINCIPAL INVESTIGATOR

• Norbert VEY, MD

  Groupe Francophone des Myelodysplasies

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 20, 2008
• First Posted: October 21, 2008
• Study Start: May 1, 2008
• Primary Completion: November 1, 2011
• Study Completion: November 1, 2011
• Last Updated: March 20, 2014

Record last verified: 2011-11

Locations

FR (14)