Myelodysplastic Syndrome (MDS)
Conditions
Keywords
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, GST P1-1 inhibitor, Apoptosis, Differentiation, Enzyme inhibitor, non-del (5q), non-deletion 5q
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).
Interventions
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.
Sponsors
Telik
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic Improvement-Erythroid (HI-E) rate | At 8 weeks of treatment | Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic Improvement-Neutrophil (HI-N) rate | At 8, 16, 24, & 32 weeks of treatment | Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006) |
| Hematologic Improvement-Platelet (HI-P) rate | At 8, 16, 24, & 32 weeks of treatment | Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006) |
| Unilineage, bilineage, trilineage, and overall HI response rate | 2 years | — |
| RBC Transfusion independence (TI) rate | At 4, 8, 12, 16, 20, 24, 28 & 32 weeks of treatment | — |
| Duration of response | 2 years | — |
| Safety of ezatiostat in this MDS population | At 4, 8, 12, 16, 20, 24, 28 & 32 weeks of treatment | Recording and grading of AEs using NCI-CTCAE v4.03 |
| Evaluation of the relationship between HI-E response, gene expression profiling and response-related variables | 2 years | — |
| Cytogenetic response rate | 16 weeks, 48 weeks and at the time of first HI response | — |
Countries
United States
Outcome results
None listed