Myelodysplastic Syndrome
Conditions
Keywords
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
Brief summary
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.
Interventions
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.
10 mg orally per day in one AM dose x 21 days with one week off therapy in a 4-week cycle.
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
* 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) \[e.g., azacitadine, decitabine, etc.\]
Design outcomes
Primary
| Measure | 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
| Measure | Time frame |
|---|---|
| Hematologic Improvement-Neutrophil (HI-N) rate | 2 years |
| Hematologic Improvement-Platelet (HI-P) rate | 2 years |
| 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 |
Countries
United States
Outcome results
None listed