Myelodysplastic Syndrome (MDS)
Conditions
Keywords
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
Brief summary
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
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.
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
NA
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic Improvement-Erythroid (HI-E) rate | At 8, 16, 24, and 32 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