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

David Miklos

Status and phase

Completed

Phase 1

Conditions

Graft vs Host Disease

Treatments

Drug: Imatinib

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00760981

IRB-14821

14821 (Other Identifier)

BMT195 (Other Identifier)

Details and patient eligibility

About

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

Enrollment

15 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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.