Phase 2 Study of Telintra® in Deletion 5q Myelodysplastic Syndrome

Study Overview
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Brief Summary
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Study TLK199.2107 is a multicenter, single arm, open-label Phase 2 study of oral ezatiostat (Telintra®) in patients with lenalidomide (Revlimid®) refractory or resistant, red blood cell (RBC) transfusion-dependent, Low to Intermediate-1 IPSS risk, del5q Myelodysplastic Syndrome (MDS).

Detailed Description
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Study TLK199.2107 is a multicenter, single arm, open-label Phase 2 study of oral ezatiostat (Telintra®) in patients with lenalidomide (Revlimid®) refractory or resistant, red blood cell (RBC) transfusion-dependent, Low to Intermediate-1 IPSS risk, del5q Myelodysplastic Syndrome (MDS). Independence from red blood cell transfusions, improvement in the levels of red blood cells, white blood cells, and platelets, and the response of the bone marrow were evaluated. Patients received a starting dose of 2000 mg total daily dose in divided doses (1000 mg orally twice daily for three weeks (21 days) on therapy followed by a one-week (7 days) off therapy rest period in four-week (28 days) treatment cycles. Patients continued treatment until documentation of lack of MDS response, MDS progression, unacceptable toxicity, or patient withdrawal from the study.

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

Conditions
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Myelodysplastic Syndrome (MDS)

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary or de Novo MDS Low or Intermediate-1 IPSS risk MDS Deletion of the 5q chromosome [del(5q) MDS] Refractory or resistant to lenalidomide (Revlimid) 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: 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 steroid use (such as tapered dosing for an acute non-MDS condition) History of hepatitis B or C, or HIV

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ezatiostat hydrochloride (Telintra®)<br>Patients received ezatiostat at a starting dose of 2000 mg total daily dose in divided doses (1000 mg PO b.i.d.) for three weeks (21 days) on therapy followed by a one-week (7 days) off therapy rest period in four-week (28 days) treatment cycles. | Drug: ezatiostat hydrochloride (Telintra®)<br>* 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.<br>* Other names: oral ezatiostat;|

What is the study measuring?
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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, 16, 24, and 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
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Keywords Provided by Centre Hospitalier Valida
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Hematology, MDS, Myelodysplastic Syndrome, Low risk MDS, Intermediate-1 risk MDS, Int-1 risk MDS, Transfusion dependence, Lenalidomide refractory, Revlimid refractory, Lenalidomide resistant, Revlimid resistant, Telintra, ezatiostat, ezatiostat hydrochloride, TLK199, Glutathione, Glutathione analog, Glutathione Transferase, Glutathione Transferase P1-1 inhibitor, GST P1-1 inhibitor, Apoptosis, Differentiation, Enzyme inhibitor