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

Graft vs Host Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00760981
• Other study ID #: IRB-14821
• Secondary ID: 14821BMT195
• Status: Completed
• Phase: Phase 1
• Start date: September 2008
• Est. completion date: April 2012

Study information

• Verified date: April 2020
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: April 2012
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

INCLUSION CRITERIA

• Chronic graft-vs-host disease (cGVHD) requiring systemic therapy occurring > 100 days after hematopoietic cell transplant 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.

• At least one of the following manifestations:

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 < 50,000/uL).

5. Abnormal liver function testing defined as alkaline phosphatase, AST, ALT, or total bilirubin > upper limit of normal (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).

• 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.

• Life expectancy = 6 months.

• Ability to understand and willingness to sign a written informed consent document.

• Karnofsky performance status = 3 50% (Appendix B).

• At least 18 years of age.

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

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

• Total bilirubin < 1.5X ULN.

• Aspartate transaminase (AST) < 2.5 x ULN.

• Alanine aminotransferase (ALT) < 2.5 x ULN.

• Alkaline phosphatase < 2.5 x ULN.

• Absolute neutrophil count (ANC) > 500/uL (growth factor supplementation is allowed).

• Hematocrit > 26% (transfusion support is allowed).

• Platelet count > 20,000/uL.

EXCLUSION CRITERIA

• Received another investigational agent = 30 days before starting the study drug.

• Ongoing intercurrent illness such as an infection not responsive to antibiotics, antiviral medicines, or antifungal medicines.

• Progressive malignant disease.

• Secondary malignancy that has not been effectively treated within the past 5 years (except localized basal cell or squamous cell carcinoma).

• Imatinib intolerance or allergy.

• Participant is breast-feeding.

• Not willing to comply with treatment or response evaluation.

• Received an allogeneic cell product [including donor lymphocyte infusion (DLI) or hematopoietic cell boost] = 100 days before starting study drug.

• Steroid and/or immunosuppressant dose has changed = 30 days before starting study drug.

Related Conditions & MeSH terms

• Graft vs Host Disease

Intervention

Drug:
• Imatinib
The single cohort for this study will receive 2 dose levels of imatinib, 200 mg orally daily followed by 400 mg orally daily.

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center (FHCRC)	Seattle	Washington
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
David Miklos	Novartis

Country where clinical trial is conducted

United States, 

References & Publications (1)

Chen GL, Arai S, Flowers ME, Otani JM, Qiu J, Cheng EC, McMillan A, Johnston LJ, Shizuru JA, Miklos DB. A phase 1 study of imatinib for corticosteroid-dependent/refractory chronic graft-versus-host disease: response does not correlate with anti-PDGFRA ant — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The frequency of adverse events graded according to the CTCAE will be the primary endpoint		Subjects will be monitored at 1, 4, 8, 16, and 24 weeks.