search
Back to results

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

Primary Purpose

Myelodysplastic Syndrome

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Ezatiostat Hydrochloride
Lenalidomide (Revlimid®)
Sponsored by
Telik
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome focused on measuring Hematology, MDS, Myelodysplastic Syndrome, Low risk MDS, Patients with non-deletion(5q), Non-deletion 5q, Non del(5q), Revlimid, lenalidomide, Telintra, ezatiostat hydrochloride, ezatiostat, TLK199, Glutathione, Glutathione analog, Glutathione Transferase, Glutathione Transferase inhibitor, Glutathione Transferase P1-1 inhibitor, GSTp1-1 inhibitor, Apoptosis, Differentiation, Enzyme inhibitor

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.]

Sites / Locations

  • Mayo Clinic
  • Loyola University Chicago Cardinal Benardin Cancer Center
  • Center for Cancer and Blood Disorders
  • Dana Farber Cancer Institute
  • Columbia University Medical Center
  • University of Rochester Medical Center
  • Cleveland Clinic
  • MDAnderson
  • Cancer Care Centers of South Texas

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Revlimid® in Combination with Telintra ®

Arm Description

Lenalidomide (Revlimid®) followed by Telintra® until MDS progression or lack of efficacy.

Outcomes

Primary Outcome Measures

To establish the maximum tolerated dose (MTD) of ezatiostat in combination with lenalidomide
To determine the safety of ezatiostat in combination with lenalidomide

Secondary Outcome Measures

To determine the efficacy of ezatiosate in combination wiht lenalidomide in patients with non-del(5q) low to intermediate-1 risk of MDS
Hematologic Improvement-Erythroid (HI-E) rate
Hematologic Improvement-Neutrophil (HI-N) rate
Hematologic Improvement-Platelet (HI-P) rate

Full Information

First Posted
February 2, 2010
Last Updated
June 4, 2013
Sponsor
Telik
search

1. Study Identification

Unique Protocol Identification Number
NCT01062152
Brief Title
Dose-Ranging Study of Telintra® Tablets + Revlimid® in Patients With Non-Deletion (5q) Low to Intermediate-1 Risk Myelodysplastic Syndrome (MDS)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
November 2009 (undefined)
Primary Completion Date
November 2012 (Actual)
Study Completion Date
March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Telik

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndrome
Keywords
Hematology, MDS, Myelodysplastic Syndrome, Low risk MDS, Patients with non-deletion(5q), Non-deletion 5q, Non del(5q), Revlimid, lenalidomide, Telintra, ezatiostat hydrochloride, ezatiostat, TLK199, Glutathione, Glutathione analog, Glutathione Transferase, Glutathione Transferase inhibitor, Glutathione Transferase P1-1 inhibitor, GSTp1-1 inhibitor, Apoptosis, Differentiation, Enzyme inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Revlimid® in Combination with Telintra ®
Arm Type
Experimental
Arm Description
Lenalidomide (Revlimid®) followed by Telintra® until MDS progression or lack of efficacy.
Intervention Type
Drug
Intervention Name(s)
Ezatiostat Hydrochloride
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide (Revlimid®)
Intervention Description
10 mg orally per day in one AM dose x 21 days with one week off therapy in a 4-week cycle.
Primary Outcome Measure Information:
Title
To establish the maximum tolerated dose (MTD) of ezatiostat in combination with lenalidomide
Time Frame
2 years
Title
To determine the safety of ezatiostat in combination with lenalidomide
Time Frame
2 years
Secondary Outcome Measure Information:
Title
To determine the efficacy of ezatiosate in combination wiht lenalidomide in patients with non-del(5q) low to intermediate-1 risk of MDS
Time Frame
2 years
Title
Hematologic Improvement-Erythroid (HI-E) rate
Time Frame
2 years
Title
Hematologic Improvement-Neutrophil (HI-N) rate
Time Frame
2 years
Title
Hematologic Improvement-Platelet (HI-P) rate
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.]
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gail Brown, M.D.
Organizational Affiliation
Telik
Official's Role
Study Director
Facility Information:
Facility Name
Mayo Clinic
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85054
Country
United States
Facility Name
Loyola University Chicago Cardinal Benardin Cancer Center
City
Maywood
State/Province
Illinois
ZIP/Postal Code
60153
Country
United States
Facility Name
Center for Cancer and Blood Disorders
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Columbia University Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
University of Rochester Medical Center
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
MDAnderson
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Cancer Care Centers of South Texas
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
22546242
Citation
Raza A, Galili N, Mulford D, Smith SE, Brown GL, Steensma DP, Lyons RM, Boccia R, Sekeres MA, Garcia-Manero G, Mesa RA. Phase 1 dose-ranging study of ezatiostat hydrochloride in combination with lenalidomide in patients with non-deletion (5q) low to intermediate-1 risk myelodysplastic syndrome (MDS). J Hematol Oncol. 2012 Apr 30;5:18. doi: 10.1186/1756-8722-5-18.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs