A Pilot Study of Imatinib Mesylate in Steroid Refractory Chronic Graft Versus Host Disease

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2010 by Stanford University.
Recruitment status was  Active, not recruiting
Sponsor:
Collaborator:
Novartis
Information provided by:
Stanford University
ClinicalTrials.gov Identifier:
NCT00760981
First received: September 25, 2008
Last updated: February 17, 2010
Last verified: February 2010
  Purpose

To determine if subjects with steroid refractory cGVHD can tolerate imatinib mesylate and whether their cGVHD responds to imatinib mesylate.


Condition Intervention Phase
Graft vs Host Disease
Drug: Imatinib
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Imatinib Mesylate in Steroid Refractory Chronic Graft Versus Host Disease

Resource links provided by NLM:


Further study details as provided by Stanford University:

Primary Outcome Measures:
  • The frequency of adverse events graded according to the CTCAE will be the primary endpoint [ Time Frame: Subjects will be monitored at 1, 4, 8, 16, and 24 weeks. ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 15
Study Start Date: September 2008
Estimated Study Completion Date: December 2009
Estimated Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:A. Subject has cGVHD requiring systemic therapy occurring >100 days after hematopoietic cell transplant diagnosed with at least one diagnostic feature from Appendix A.

B. Subject has active cGVHD with either:

  1. Persistent steroid dependence defined as the inability to taper steroid treatment to less than 0.25 mg/kg/d prednisone or its equivalent for at least 3 months
  2. Progression of cGVHD signs and symptoms on steroid therapy equivalent to prednisone 0.5 mg/kg/d for at least 1 month.

C. Subject has at least one of the following manifestations with which to follow progression of disease or response to imatinib:

  1. Skin changes (rash, sclerosis, fasciitis, or ulceration)
  2. Abnormal eye wetness <= 5 mm as measured by Schirmer's test
  3. Oral mucosal changes (erythema, lichenoid changes, ulcers, or mucoceles)
  4. Thrombocytopenia (platelets <150,000/uL).
  5. Abnormal liver function testing (alkaline phosphatase, AST, ALT, or total bilirubin > ULN).
  6. Bronchiolitis obliterans (diagnosed by a > 5% annual decline in FEV1 with the lowest post-transplant FEV1/FVC < 0.8 and an appropriate CT scan or lung biopsy, see Appendix A for details)

D. Subject may have previously any received immunosuppressive therapies for cGVHD. Continuing treatment with steroids and any one or none of the following is allowed: cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, or extracorporeal photopheresis.

E. Subject has been on a fixed dose of steroids or a fixed dose of steroids and one other immunosuppressant (cyclosporine, tacrolimus, sirolimus, mycophenolate mofetil, or extracorporeal photopheresis) for >= 30 days before starting imatinib.

F. Subject has a life expectancy >= 6 months.

G. Subject has the ability to understand and willingness to sign a written informed consent document.

H. Subject has a Karnofsky performance status^3 50% (Appendix B).

I. Subject is ³ 18 years of age.

J. If a female with reproductive potential (defined as having at least 1 menstrual period in the past 12 months), the subject must have a negative pregnancy test performed <= 7 days before starting study drug.

K. If a female with reproductive potential, the subject agrees to use contraception for the duration of the trial.

L. Subject has a total bilirubin < 1.5X ULN.

M. Subject has an aspartate transaminase (AST), alanine aminotransferase (ALT), and alkaline phosphatase < 2.5X ULN.

N. Subject has an absolute neutrophil count > 500/uL (growth factor supplementation is allowed).

O. Subject has a hematocrit > 26% (transfusion support is allowed).

P. Subject has a platelet count > 20,000/uL.

Exclusion Criteria:A. Subject has received another investigational agent <= 30 days before starting the study drug.

B. Subject has an on-going, intercurrent illness such as an infection not responsive to antibiotics, antiviral medicines, or antifungal medicines.

C. Subject has progressive malignant disease.

D. Subject has a secondary malignancy that has not been effectively treated within the past 5 years (except localized basal cell or squamous cell carcinoma).

E. Subject has imatinib intolerance or allergy.

F. Subject is breast-feeding.

G. Subject is not willing to comply with treatment or response evaluation.

H. Subject has received an allogeneic cell product (including DLI or hematopoietic cell boost) <= 100 days before starting study drug.

I. The subject's steroid and/or immunosuppressant dose has changed <= 30 days before starting study drug.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00760981

Locations
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
United States, Washington
Fred Hutchinson Cancer Research Center (FHCRC)
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Stanford University
Novartis
Investigators
Principal Investigator: David Miklos Stanford University
  More Information

No publications provided by Stanford University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: David Miklos, Stanford University School of Medicine
ClinicalTrials.gov Identifier: NCT00760981     History of Changes
Other Study ID Numbers: SU-07112008-1254, BMT195
Study First Received: September 25, 2008
Last Updated: February 17, 2010
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Imatinib
Antineoplastic Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protein Kinase Inhibitors
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014