Clinical trial NCT01422486: Phase 2 Study of Telintra® in Deletion 5q Myelodysplastic Syndrome
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Myelodysplastic Syndrome (MDS)
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
Lead sponsor: Telik
Sponsor class: INDUSTRY
First posted: 2011-08-24
Enrollment: 2
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Hematologic Improvement-Erythroid (HI-E) rate
timeFrame: At 8, 16, 24, and 32 weeks of treatment
Secondary outcomes:
measure: RBC Transfusion independence (TI) rate
timeFrame: At 4, 8, 12, 16, 20, 24, 28 & 32 weeks of treatment
measure: Hematologic Improvement-Neutrophil (HI-N) rate
timeFrame: At 8, 16, 24, & 32 weeks of treatment
measure: Hematologic Improvement-Platelet (HI-P) rate
timeFrame: At 8, 16, 24, & 32 weeks of treatment
measure: Unilineage, bilineage, trilineage, and overall HI response rate
timeFrame: 2 years
measure: Cytogenetic response rate
timeFrame: 16 weeks, 48 weeks and at the time of first HI response
measure: Duration of response
timeFrame: 2 years
measure: Safety of ezatiostat in this MDS population
timeFrame: At 4, 8, 12, 16, 20, 24, 28 & 32 weeks of treatment
measure: Evaluation of the relationship between HI-E response, gene expression profiling and response-related variables
timeFrame: 2 years
Other outcomes:
Locations:
city: Maywood
country: United States
facility: Loyola University
state: Illinois
city: Springfield
country: United States
facility: SIU School of Medicine, Simmons Cancer Center
state: Illinois
city: Bethesda
country: United States
facility: Center for Cancer and Blood Disorders
state: Maryland
city: New York
country: United States
facility: Columbia University
state: New York
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
Study officials:
affiliation: Telik
name: Gail L Brown, MD
role: STUDY_DIRECTOR
References: