Dose-Ranging Study of Telintra® Tablets + Revlimid® in Patients With Non-Deletion (5q) Low to Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

Myelodysplastic Syndrome Clinical Trial

Official title:

Phase 1 Dose-Ranging Study of Ezatiostat Hydrochloride (Telintra®, TLK199 Tablets)in Combination With Lenalidomide (Revlimid®)in Patients With Non-Deletion(5q) Low to Intermediate-1 Risk Myelodysplastic Syndrome (MDS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01062152
• Other study ID #: TLK199.1104
• Status: Completed
• Phase: Phase 1
• First received: February 2, 2010
• Last updated: June 4, 2013
• Start date: November 2009
• Est. completion date: March 2013

Study information

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

Clinical Trial Summary

This is an open label, multicenter Phase 1 dose escalation study evaluating five doses of ezatiostat in combination with lenalidomide in patients with non-del(5q) low to intermediate 1 risk MDS. The HI-E, HI-N, HI-P rates [by International Working Group (IWG) 2006 criteria] and safety of each treatment group will be evaluated to select the optimal dose of ezatiostat in combination with lenalidomide for future studies.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 19
• Est. completion date: March 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologic diagnosis of primary or de novo MDS using WHO classification

• Non-del(5q) low or Intermediate-1risk MDS

• ECOG performance status of 0-1

• Documented significant cytopenia for at least 2 months

• Must have discontinued growth factors (EPO, G-CSF, GM-CSF) for at least 21 days prior to study entry

• All study participants must be registered into the mandatory RevAssist® program and be willing and able to comply with the requirements of RevAssist®

• Females of childbearing potential should have two negative serum pregnancy tests with a sensitivity of at least 50 mIU/mL. The first test should be performed within 10-14 days, and the second test within 24 hours of prescribing lenalidomide (prescriptions must be filled within seven days)

Exclusion Criteria:

• Known hypersensitivity to Telintra™ (intravenous or oral)

• Known prior therapy with or hypersensitivity to thalidomide or lenalidomide

• Prior allogenic bone marrow transplant for MDS

• History or prior malignancy

• Except for treated carcinoma of uterine cervix, basal cell or squamous cell skin cancer, or other cancers (e.g. breast, prostate) for which patient has been disease-free for at least 3 years.

• MDS evolving from:

• A pre-existing myeloproliferative disorder

• An autoimmune disease

• Secondary to prior treatment with radiation or chemotherapy

• History of MDS IPSS score>1.0

• Pregnant or lactating women

• Leptomeningeal or leukemic meningitis

• Prior treatment with DNA methyltransferase inhibitors (DMTI) [e.g., azacitadine, decitabine, etc.]

Study Design

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

Related Conditions & MeSH terms

• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Ezatiostat Hydrochloride
Starting dose 2000 mg orally in divided doses twice daily (1000 mg in AM & 1000 mg in PM) x 21 days with one week off therapy in a 4-week cycle.
• Lenalidomide (Revlimid®)
10 mg orally per day in one AM dose x 21 days with one week off therapy in a 4-week cycle.

Locations

Country	Name	City	State
United States	Center for Cancer and Blood Disorders	Bethesda	Maryland
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Cleveland Clinic	Cleveland	Ohio
United States	MDAnderson	Houston	Texas
United States	Loyola University Chicago Cardinal Benardin Cancer Center	Maywood	Illinois
United States	Columbia University Medical Center	New York	New York
United States	Mayo Clinic	Phoenix	Arizona
United States	University of Rochester Medical Center	Rochester	New York
United States	Cancer Care Centers of South Texas	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Telik

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To establish the maximum tolerated dose (MTD) of ezatiostat in combination with lenalidomide		2 years	No
Primary	To determine the safety of ezatiostat in combination with lenalidomide		2 years	No
Secondary	To determine the efficacy of ezatiosate in combination wiht lenalidomide in patients with non-del(5q) low to intermediate-1 risk of MDS		2 years	No
Secondary	Hematologic Improvement-Erythroid (HI-E) rate		2 years	No
Secondary	Hematologic Improvement-Neutrophil (HI-N) rate		2 years	No
Secondary	Hematologic Improvement-Platelet (HI-P) rate		2 years	No