Clinical trial NCT00760981: A Pilot Study of Imatinib Mesylate in Steroid Refractory Chronic Graft Versus Host Disease
Official title: A Pilot Study of Imatinib Mesylate in Steroid Refractory Chronic Graft Versus Host Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Graft vs Host Disease
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Novartis
First posted: 2008-09-26
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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


Eligibility 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.

Primary outcomes:
measure: The frequency of adverse events graded according to the CTCAE will be the primary endpoint
timeFrame: Subjects will be monitored at 1, 4, 8, 16, and 24 weeks.
Secondary outcomes:
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Seattle
country: United States
facility: Fred Hutchinson Cancer Research Center (FHCRC)
state: Washington
Study officials:
affiliation: Stanford University
name: David Miklos, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 antibodies. Blood. 2011 Oct 13;118(15):4070-8. doi: 10.1182/blood-2011-03-341693. Epub 2011 Aug 9.