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

• ClinicalTrials.gov Identifier: NCT01422486
• Recruitment Status: Terminated
• First Posted: August 24, 2011
• Last Update Posted: November 25, 2013
• Sponsor: Telik
• Information provided by (Responsible Party): Telik

Tracking Information

• First Submitted Date: August 18, 2011
• First Posted Date: August 24, 2011
• Last Update Posted Date: November 25, 2013
• Study Start Date: October 2011
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 20, 2013)

Hematologic Improvement-Erythroid (HI-E) rate [ Time Frame: At 8, 16, 24, and 32 weeks of treatment ]

Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006)

Original Primary Outcome Measures (submitted: August 22, 2011)

Hematologic Improvement-Erythroid (HI-E) rate [ Time Frame: Every 8 weeks ]

Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006)

Current Secondary Outcome Measures (submitted: October 24, 2011)

• RBC Transfusion independence (TI) rate [ Time Frame: At 4, 8, 12, 16, 20, 24, 28 & 32 weeks of treatment ]
• Hematologic Improvement-Neutrophil (HI-N) rate [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 2 years ]
• Cytogenetic response rate [ Time Frame: 16 weeks, 48 weeks and at the time of first HI response ]
• Duration of response [ Time Frame: 2 years ]
• Safety of ezatiostat in this MDS population [ Time Frame: 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 [ Time Frame: 2 years ]

Original Secondary Outcome Measures (submitted: August 22, 2011)

• RBC Transfusion independence (TI) rate [ Time Frame: Every 4 weeks ]
• Hematologic Improvement-Neutrophil (HI-N) rate [ Time Frame: Every 8 weeks ]
  Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006)
• Hematologic Improvement-Platelet (HI-P) rate [ Time Frame: Every 8 weeks ]
  Hematologic Improvement response will be assessed per the IWG MDS response criteria (2006)
• Unilineage, bilineage, trilineage, and overall HI response rate [ Time Frame: 2 years ]
• Cytogenetic response rate [ Time Frame: 16 weeks, 48 weeks and at the time of first HI response ]
• Duration of response [ Time Frame: 2 years ]
• Safety of ezatiostat in this MDS population [ Time Frame: Every 4 weeks ]
  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 [ Time Frame: 2 years ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Myelodysplastic Syndrome (MDS)

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.

Other Names:

• Telintra
• Telinta Tablets
• Oral Telintra
• ezatiostat
• ezatiostat hydrochloride
• oral ezatiostat

Study Arms

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.

Intervention: Drug: ezatiostat hydrochloride (Telintra®)

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: November 20, 2013): 2
• Original Estimated Enrollment (submitted: August 22, 2011): 130
• Actual Study Completion Date: February 2013
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01422486
• Other Study ID Numbers: TLK199.2107
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Telik
• Original Responsible Party: Same as current
• Current Study Sponsor: Telik
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Gail L Brown, MD; Telik

• PRS Account: Telik
• Verification Date: November 2013