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

Myelodysplastic Syndrome (MDS) Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01422486
• Other study ID #: TLK199.2107
• Status: Terminated
• Phase: Phase 2
• First received: August 18, 2011
• Last updated: November 20, 2013
• Start date: October 2011
• Est. completion date: February 2013

Study information

• Verified date: November 2013
• Source: Telik
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 2
• Est. completion date: February 2013
• Est. primary completion date: February 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Myelodysplastic Syndrome (MDS)
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• ezatiostat hydrochloride (Telintra®)
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.

Locations

Country	Name	City	State
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Loyola University	Maywood	Illinois
United States	Vanderbilt University	Nashville	Tennessee
United States	Columbia University	New York	New York
United States	SIU School of Medicine, Simmons Cancer Center	Springfield	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Telik

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hematologic Improvement-Erythroid (HI-E) rate	Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006)	At 8, 16, 24, and 32 weeks of treatment	No
Secondary	RBC Transfusion independence (TI) rate		At 4, 8, 12, 16, 20, 24, 28 & 32 weeks of treatment	No
Secondary	Hematologic Improvement-Neutrophil (HI-N) rate	Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006)	At 8, 16, 24, & 32 weeks of treatment	No
Secondary	Hematologic Improvement-Platelet (HI-P) rate	Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006)	At 8, 16, 24, & 32 weeks of treatment	No
Secondary	Unilineage, bilineage, trilineage, and overall HI response rate		2 years	No
Secondary	Cytogenetic response rate		16 weeks, 48 weeks and at the time of first HI response	No
Secondary	Duration of response		2 years	No
Secondary	Safety of ezatiostat in this MDS population	Recording and grading of AEs using NCI-CTCAE v4.03	At 4, 8, 12, 16, 20, 24, 28 & 32 weeks of treatment	No
Secondary	Evaluation of the relationship between HI-E response, gene expression profiling and response-related variables		2 years	No