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

Sponsor

Telik (Industry)

Overall Status

Terminated

CT.gov ID

NCT01422486

Collaborator

(none)

Enrollment

Locations

Arm

16.1

Duration (Months)

0.4

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome (MDS)	Drug: ezatiostat hydrochloride (Telintra®)	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

2 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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 Start Date :

Oct 1, 2011

Actual Primary Completion Date :

Feb 1, 2013

Actual Study Completion Date :

Feb 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	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. Other Names: Telintra Telinta Tablets Oral Telintra ezatiostat ezatiostat hydrochloride oral ezatiostat

Arm

Intervention/Treatment

Experimental: 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.

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.

Other Names:

Telintra

Telinta Tablets

Oral Telintra

ezatiostat

ezatiostat hydrochloride

oral ezatiostat

Outcome Measures

Primary Outcome Measures

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

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)
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]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Loyola University	Maywood	Illinois	United States	60153
2	SIU School of Medicine, Simmons Cancer Center	Springfield	Illinois	United States	62794-9677
3	Center for Cancer and Blood Disorders	Bethesda	Maryland	United States	20817
4	Columbia University	New York	New York	United States	10032
5	Vanderbilt University	Nashville	Tennessee	United States	37232