Study of (Telintra®) in Non-Del(5q) Myelodysplastic Syndrome

Study Overview
=================
Brief Summary
-----------------
This is a multicenter, single arm open label Phase 2b Study of oral ezatiostat (Telintra®) in Patients who are RBC tranfusion dependent, Low to INT-1 IPSS risk, non-del (5q) Myelodysplastic Syndrome (MDS).

Official Title
-----------------
Phase 2b Study of Oral Ezatiostat Hydrochloride (Telintra®) in Patients With Low to Intermediate-1 Risk, Non-Deletion 5q Myelodysplastic Syndrome

Conditions
-----------------
Myelodysplastic Syndrome (MDS)

Intervention / Treatment
-----------------
* Drug: ezatiostat hydrochloride (Telintra®)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Primary or de Novo MDS Low to Intermediate-1 IPSS risk of MDS ECOG performance score of 0 or 1 Documentation of significant anemia with or without additional cytopenia Adequate kidney and liver function Patients must have discontinued hematopoietic growth factors at least 3 weeks prior to study entry Exclusion Criteria: Deletion of the 5q chromosome [del(5q) MDS] Prior allogenic bone marrow transplant for MDS Known sensitivity to ezatiostat (injection or oral tablets) Prior treatment with hypomethylating agent (HMA) (e.g., azacitadine, decitabine) History of MDS IPSS risk score of greater than 1.0 Pregnant or lactating women Any severe concurrent disease, infection or comorbidity that, in the judgement of the investigator, would make the patient inappropriate for study entry Oral steroids greater than 10 mg per day. Exceptions: those prescribed for other conditions (such as new adrenal failure, asthma, arthritis) or brief sterioid use (such as tapered dosing for an acute non-MDS condition) History of hepatitis B or C, or HIV

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: ezatiostat hydrochloride (Telintra®)|Three weeks of treatment with ezatiostat at 2000 mg per day in divided doses followed by a one week rest period in four-week treatment cycles.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematologic Improvement-Erythroid (HI-E) rate | Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006) | At 8 weeks of treatment | 
| Hematologic Improvement-Erythroid (HI-E) rate | Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006) | At 16 weeks of treatment | 
| Hematologic Improvement-Erythroid (HI-E) rate | Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006) | At 24 weeks of treatment | 
| Hematologic Improvement-Erythroid (HI-E) rate | Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006) | At 32 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RBC Transfusion independence (TI) rate |  | At 4, 8, 12, 16, 20, 24, 28 & 32 weeks of treatment | 
| Hematologic Improvement-Neutrophil (HI-N) rate | Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006) | At 8, 16, 24, & 32 weeks of treatment | 
| Hematologic Improvement-Platelet (HI-P) rate | Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006) | At 8, 16, 24, & 32 weeks of treatment | 
| Unilineage, bilineage, trilineage, and overall HI response rate |  | 2 years | 
| Cytogenetic response rate |  | 16 weeks, 48 weeks and at the time of first HI response | 
| Duration of response |  | 2 years | 
| Safety of ezatiostat in this MDS population | Recording and grading of AEs using NCI-CTCAE v4.03 | At 4, 8, 12, 16, 20, 24, 28 & 32 weeks of treatment | 
| Evaluation of the relationship between HI-E response, gene expression profiling and response-related variables |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
GST P1-1 inhibitor, Hematology, MDS, Myelodysplastic Syndrome, Low risk MDS, Int-1 risk MDS, Transfusion dependence, Telintra, ezatiostat, ezatiostat hydrochloride, TLK199, Glutathione, Glutathione analog, Glutathione Transferase, Glutathione Transferase P1-1 inhibitor, Apoptosis, Differentiation, Enzyme inhibitor, non-del (5q), non-deletion 5q