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

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)

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.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Ezatiostat Hydrochloride; Drug: Lenalidomide (Revlimid®)

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • Illinois
    • Maywood, Illinois, United States, 60153
      • Loyola University Chicago Cardinal Benardin Cancer Center
  • Maryland
    • Bethesda, Maryland, United States, 20817
      • Center for Cancer and Blood Disorders
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Dana Farber Cancer Institute
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Texas
    • Houston, Texas, United States, 77030
      • MDAnderson
    • San Antonio, Texas, United States, 78229
      • Cancer Care Centers of South Texas

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.]

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To establish the maximum tolerated dose (MTD) of ezatiostat in combination with lenalidomide	2 years
To determine the safety of ezatiostat in combination with lenalidomide	2 years

Secondary Outcome Measures

Outcome Measure	Time Frame
To determine the efficacy of ezatiosate in combination wiht lenalidomide in patients with non-del(5q) low to intermediate-1 risk of MDS	2 years
Hematologic Improvement-Erythroid (HI-E) rate	2 years
Hematologic Improvement-Neutrophil (HI-N) rate	2 years
Hematologic Improvement-Platelet (HI-P) rate	2 years

Collaborators and Investigators

• Sponsor: Telik
• Investigators: Study Director: Gail Brown, M.D., Telik

Publications and helpful links

General Publications

• Raza A, Galili N, Mulford D, Smith SE, Brown GL, Steensma DP, Lyons RM, Boccia R, Sekeres MA, Garcia-Manero G, Mesa RA. Phase 1 dose-ranging study of ezatiostat hydrochloride in combination with lenalidomide in patients with non-deletion (5q) low to intermediate-1 risk myelodysplastic syndrome (MDS). J Hematol Oncol. 2012 Apr 30;5:18. doi: 10.1186/1756-8722-5-18.

Study record dates

Study Major Dates

• Study Start: November 1, 2009
• Primary Completion (Actual): November 1, 2012
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: February 2, 2010
• First Submitted That Met QC Criteria: February 3, 2010
• First Posted (Estimate): February 4, 2010

Study Record Updates

• Last Update Posted (Estimate): June 6, 2013
• Last Update Submitted That Met QC Criteria: June 4, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: lenalidomide; MDS; Hematology; Myelodysplastic Syndrome; Revlimid; Glutathione; Apoptosis; Differentiation; Telintra; ezatiostat hydrochloride; ezatiostat; TLK199; Glutathione analog; Glutathione Transferase; Glutathione Transferase inhibitor; Glutathione Transferase P1-1 inhibitor; GSTp1-1 inhibitor; Enzyme inhibitor; Low risk MDS; Patients with non-deletion(5q); Non-deletion 5q; Non del(5q)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Physiological Effects of Drugs; Antineoplastic Agents; Immunologic Factors; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Lenalidomide
• Other Study ID Numbers: TLK199.1104