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

Study Overview
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Brief Summary
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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.

Official Title
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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)

Conditions
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Myelodysplastic Syndrome

Intervention / Treatment
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* Drug: Ezatiostat Hydrochloride
* Drug: Lenalidomide (Revlimid®)


Participation Criteria
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Eligibility Criteria
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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.]

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Revlimid® in Combination with Telintra ®<br>Lenalidomide (Revlimid®) followed by Telintra® until MDS progression or lack of efficacy. | Drug: Ezatiostat Hydrochloride<br>* 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.<br>Drug: Lenalidomide (Revlimid®)<br>* 10 mg orally per day in one AM dose x 21 days with one week off therapy in a 4-week cycle.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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