Phase 2 Study of Telintra® in Deletion 5q Myelodysplastic Syndrome

Phase 2

Terminated

• Conditions: Myelodysplastic Syndrome (MDS)
• Interventions: Drug: ezatiostat hydrochloride (Telintra®)

• Registration Number: NCT01422486
• Lead Sponsor: Telik

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.

Study Timeline

• Study First Submitted: 2011-08-18
• Study First Submitted QC: 2011-08-22
• Study First Posted: 2011-08-24
• Study Start: 2011-10
• Primary Completion: 2013-02
• Study Completion: 2013-02
• Status Verified: 2013-11
• Last Update Submitted: 2013-11-20
• Last Update Posted: 2013-11-25

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 2

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
ezatiostat hydrochloride (Telintra®)	ezatiostat hydrochloride (Telintra®)	Patients received ezatiostat at a starting dose of 2000 mg total daily dose in divided doses (1000 mg PO b.i.d.) 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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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
Cytogenetic response rate	16 weeks, 48 weeks and at the time of first HI response
Duration of response	2 years
RBC Transfusion independence (TI) rate	At 4, 8, 12, 16, 20, 24, 28 & 32 weeks of treatment
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)
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

Trial Locations

Locations (5)

SIU School of Medicine, Simmons Cancer Center; 🇺🇸 Springfield, Illinois, United States

Columbia University; 🇺🇸 New York, New York, United States

Loyola University; 🇺🇸 Maywood, Illinois, United States

Center for Cancer and Blood Disorders; 🇺🇸 Bethesda, Maryland, United States

Vanderbilt University; 🇺🇸 Nashville, Tennessee, United States