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A Pilot Study of Imatinib Mesylate in Steroid Refractory Chronic Graft Versus Host Disease
This study is currently recruiting participants.
Verified by Stanford University, December 2008
Sponsors and Collaborators: Stanford University
Novartis
Information provided by: Stanford University
ClinicalTrials.gov Identifier: NCT00760981
  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 I

Drug Information available for: Imatinib Imatinib mesylate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study
Official Title: A Pilot Study of Imatinib Mesylate in Steroid Refractory Chronic Graft Versus Host Disease

Further study details as provided by Stanford University:

Primary Outcome Measures:
  • Determine the safety and tolerability of imatinib in steroid refractory cGVHD

Secondary Outcome Measures:
  • Determine the overall response rate of steroid refractory cGVHD to imatinib.
  • Determine the treatment failure rate of imatinib for steroid refractory cGVHD.
  • Assess steroid reduction as a surrogate for cGVHD response to imatinib.
  • Evaluate subject reported quality of life outcomes.

Estimated Enrollment: 15
Study Start Date: September 2008
  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.&#xA; 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00760981

Locations
United States, California
Stanford University School of Medicine Recruiting
Stanford, California, United States, 94305
Contact: Joanne Fehling, RN, MSN     650-721-2372     jfehling@stanford.edu    
Contact: Cancer Clinical Trials Office     (650) 498-7061        
Principal Investigator: David Miklos            
Sub-Investigator: Wen-Kai Weng            
Sub-Investigator: Judith Anne Shizuru            
Sub-Investigator: William Hewitt Robinson            
Sub-Investigator: Robert S Negrin            
Sub-Investigator: Robert Lowsky            
Sub-Investigator: Ginna Laport            
Sub-Investigator: Laura Johnston            
Sub-Investigator: David Franklin Fiorentino            
Sub-Investigator: Howard Y. Chang            
Sub-Investigator: Jonathan Eliot Benjamin            
Sub-Investigator: Sally Arai            
Sponsors and Collaborators
Stanford University
Novartis
Investigators
Principal Investigator: David Miklos Stanford University
  More Information

Study ID Numbers: SU-07112008-1254, BMT195, NCT00760981
Study First Received: September 25, 2008
Last Updated: December 19, 2008
ClinicalTrials.gov Identifier: NCT00760981  
Health Authority: United States: Institutional Review Board

Study placed in the following topic categories:
Imatinib
Graft versus host disease
Graft vs Host Disease
Homologous wasting disease

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

ClinicalTrials.gov processed this record on January 14, 2009