Dose-Ranging Study of Telintra® Tablets + Revlimid® in Patients With Non-Deletion (5q) Low to Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Telik
ClinicalTrials.gov Identifier:
NCT01062152
First received: February 2, 2010
Last updated: June 4, 2013
Last verified: June 2013
  Purpose

This is an open label, multicenter Phase 1 dose escalation study evaluating five doses of ezatiostat in combination with lenalidomide in patients with non-del(5q) low to intermediate 1 risk MDS. The HI-E, HI-N, HI-P rates [by International Working Group (IWG) 2006 criteria] and safety of each treatment group will be evaluated to select the optimal dose of ezatiostat in combination with lenalidomide for future studies.


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: Ezatiostat Hydrochloride
Drug: Lenalidomide (Revlimid®)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 1 Dose-Ranging Study of Ezatiostat Hydrochloride (Telintra®, TLK199 Tablets)in Combination With Lenalidomide (Revlimid®)in Patients With Non-Deletion(5q) Low to Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

Resource links provided by NLM:


Further study details as provided by Telik:

Primary Outcome Measures:
  • To establish the maximum tolerated dose (MTD) of ezatiostat in combination with lenalidomide [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To determine the safety of ezatiostat in combination with lenalidomide [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the efficacy of ezatiosate in combination wiht lenalidomide in patients with non-del(5q) low to intermediate-1 risk of MDS [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Hematologic Improvement-Erythroid (HI-E) rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Hematologic Improvement-Neutrophil (HI-N) rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • Hematologic Improvement-Platelet (HI-P) rate [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 19
Study Start Date: November 2009
Study Completion Date: March 2013
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Revlimid® in Combination with Telintra ®
Lenalidomide (Revlimid®) followed by Telintra® until MDS progression or lack of efficacy.
Drug: Ezatiostat Hydrochloride
Starting dose 2000 mg orally in divided doses twice daily (1000 mg in AM & 1000 mg in PM) x 21 days with one week off therapy in a 4-week cycle.
Drug: Lenalidomide (Revlimid®)
10 mg orally per day in one AM dose x 21 days with one week off therapy in a 4-week cycle.

  Eligibility

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

Inclusion Criteria:

  • Histologic diagnosis of primary or de novo MDS using WHO classification
  • Non-del(5q) low or Intermediate-1risk MDS
  • ECOG performance status of 0-1
  • Documented significant cytopenia for at least 2 months
  • Must have discontinued growth factors (EPO, G-CSF, GM-CSF) for at least 21 days prior to study entry
  • All study participants must be registered into the mandatory RevAssist® program and be willing and able to comply with the requirements of RevAssist®
  • Females of childbearing potential should have two negative serum pregnancy tests with a sensitivity of at least 50 mIU/mL. The first test should be performed within 10-14 days, and the second test within 24 hours of prescribing lenalidomide (prescriptions must be filled within seven days)

Exclusion Criteria:

  • Known hypersensitivity to Telintra™ (intravenous or oral)
  • Known prior therapy with or hypersensitivity to thalidomide or lenalidomide
  • Prior allogenic bone marrow transplant for MDS
  • History or prior malignancy

    • Except for treated carcinoma of uterine cervix, basal cell or squamous cell skin cancer, or other cancers (e.g. breast, prostate) for which patient has been disease-free for at least 3 years.
  • MDS evolving from:

    • A pre-existing myeloproliferative disorder
    • An autoimmune disease
    • Secondary to prior treatment with radiation or chemotherapy
  • History of MDS IPSS score>1.0
  • Pregnant or lactating women
  • Leptomeningeal or leukemic meningitis
  • Prior treatment with DNA methyltransferase inhibitors (DMTI) [e.g., azacitadine, decitabine, etc.]
  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: NCT01062152

Locations
United States, Arizona
Mayo Clinic
Phoenix, Arizona, United States, 85054
United States, Illinois
Loyola University Chicago Cardinal Benardin Cancer Center
Maywood, Illinois, United States, 60153
United States, Maryland
Center for Cancer and Blood Disorders
Bethesda, Maryland, United States, 20817
United States, Massachusetts
Dana Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, New York
Columbia University Medical Center
New York, New York, United States, 10032
University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
United States, Texas
MDAnderson
Houston, Texas, United States, 77030
Cancer Care Centers of South Texas
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Telik
Investigators
Study Director: Gail Brown, M.D. Telik
  More Information

No publications provided by Telik

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Telik
ClinicalTrials.gov Identifier: NCT01062152     History of Changes
Other Study ID Numbers: TLK199.1104
Study First Received: February 2, 2010
Last Updated: June 4, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Telik:
Hematology
MDS
Myelodysplastic Syndrome
Low risk MDS
Patients with non-deletion(5q)
Non-deletion 5q
Non del(5q)
Revlimid
lenalidomide
Telintra
ezatiostat hydrochloride
ezatiostat
TLK199
Glutathione
Glutathione analog
Glutathione Transferase
Glutathione Transferase inhibitor
Glutathione Transferase P1-1 inhibitor
GSTp1-1 inhibitor
Apoptosis
Differentiation
Enzyme inhibitor

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Lenalidomide
Thalidomide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors

ClinicalTrials.gov processed this record on July 24, 2014