Clinical trial NCT01062152: Dose-Ranging Study of Telintra® Tablets + Revlimid® in Patients With Non-Deletion (5q) Low to Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
Official title: Phase 1 Dose-Ranging Study of Ezatiostat Hydrochloride (Telintra®, TLK199 Tablets)in Combination With Lenalidomide (Revlimid®)in Patients With Non-Deletion(5q) Low to Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Myelodysplastic Syndrome
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
Lead sponsor: Telik
Sponsor class: INDUSTRY
First posted: 2010-02-04
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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) \[e.g., azacitadine, decitabine, etc.\]

Primary outcomes:
measure: To establish the maximum tolerated dose (MTD) of ezatiostat in combination with lenalidomide
timeFrame: 2 years
measure: To determine the safety of ezatiostat in combination with lenalidomide
timeFrame: 2 years
Secondary outcomes:
measure: To determine the efficacy of ezatiosate in combination wiht lenalidomide in patients with non-del(5q) low to intermediate-1 risk of MDS
timeFrame: 2 years
measure: Hematologic Improvement-Erythroid (HI-E) rate
timeFrame: 2 years
measure: Hematologic Improvement-Neutrophil (HI-N) rate
timeFrame: 2 years
measure: Hematologic Improvement-Platelet (HI-P) rate
timeFrame: 2 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic
state: Arizona
city: Maywood
country: United States
facility: Loyola University Chicago Cardinal Benardin Cancer Center
state: Illinois
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Rochester
country: United States
facility: University of Rochester Medical Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Houston
country: United States
facility: MDAnderson
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas
state: Texas
Study officials:
affiliation: Telik
name: Gail Brown, M.D.
role: STUDY_DIRECTOR
References:
citation: Raza A, Galili N, Mulford D, Smith SE, Brown GL, Steensma DP, Lyons RM, Boccia R, Sekeres MA, Garcia-Manero G, Mesa RA. Phase 1 dose-ranging study of ezatiostat hydrochloride in combination with lenalidomide in patients with non-deletion (5q) low to intermediate-1 risk myelodysplastic syndrome (MDS). J Hematol Oncol. 2012 Apr 30;5:18. doi: 10.1186/1756-8722-5-18.