NCT01062152

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
19

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Nov 2009

Typical duration for phase_1

Geographic Reach
1 country

9 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2009

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

February 2, 2010

Completed
2 days until next milestone

First Posted

Study publicly available on registry

February 4, 2010

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 1, 2012

Completed
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2013

Completed
Last Updated

June 6, 2013

Status Verified

June 1, 2013

Enrollment Period

3 years

First QC Date

February 2, 2010

Last Update Submit

June 4, 2013

Conditions

Keywords

HematologyMDSMyelodysplastic SyndromeLow risk MDSPatients with non-deletion(5q)Non-deletion 5qNon del(5q)RevlimidlenalidomideTelintraezatiostat hydrochlorideezatiostatTLK199GlutathioneGlutathione analogGlutathione TransferaseGlutathione Transferase inhibitorGlutathione Transferase P1-1 inhibitorGSTp1-1 inhibitorApoptosisDifferentiationEnzyme inhibitor

Outcome Measures

Primary Outcomes (2)

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

    2 years

  • To determine the safety of ezatiostat in combination with lenalidomide

    2 years

Secondary Outcomes (4)

  • 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

  • Hematologic Improvement-Erythroid (HI-E) rate

    2 years

  • Hematologic Improvement-Neutrophil (HI-N) rate

    2 years

  • Hematologic Improvement-Platelet (HI-P) rate

    2 years

Study Arms (1)

Revlimid® in Combination with Telintra ®

EXPERIMENTAL

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

Drug: Ezatiostat HydrochlorideDrug: Lenalidomide (Revlimid®)

Interventions

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.

Revlimid® in Combination with Telintra ®

10 mg orally per day in one AM dose x 21 days with one week off therapy in a 4-week cycle.

Revlimid® in Combination with Telintra ®

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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)

You may not qualify if:

  • 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) \[e.g., azacitadine, decitabine, etc.\]

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (9)

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

Loyola University Chicago Cardinal Benardin Cancer Center

Maywood, Illinois, 60153, United States

Location

Center for Cancer and Blood Disorders

Bethesda, Maryland, 20817, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MDAnderson

Houston, Texas, 77030, United States

Location

Cancer Care Centers of South Texas

San Antonio, Texas, 78229, United States

Location

Related Publications (1)

  • 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.

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

gamma-Glu-S-BzCys-PhGly diethyl esterLenalidomide

Condition Hierarchy (Ancestors)

Bone Marrow DiseasesHematologic DiseasesHemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

PhthalimidesPhthalic AcidsAcids, CarbocyclicCarboxylic AcidsOrganic ChemicalsPiperidonesPiperidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIsoindolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Study Officials

  • Gail Brown, M.D.

    Telik

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

February 2, 2010

First Posted

February 4, 2010

Study Start

November 1, 2009

Primary Completion

November 1, 2012

Study Completion

March 1, 2013

Last Updated

June 6, 2013

Record last verified: 2013-06

Locations