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

NCT00760981 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: IRB-1482114821BMT195
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Graft vs Host Disease

Outcome Measures

Primary Outcomes (1)

• 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.

Study Arms (1)

Imatinib

EXPERIMENTAL

200 mg orally daily and 400 mg orally daily for 4 weeks.

Drug: Imatinib

Interventions

Imatinib DRUG

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

Also known as: Gleevec

Imatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Chronic graft-vs-host disease (cGVHD) requiring systemic therapy occurring \> 100 days after hematopoietic cell transplant with either:
• 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.
• 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:
• Skin changes (rash, sclerosis, fasciitis, or ulceration).
• Abnormal eye wetness ≤ 5 mm as measured by Schirmer's test.
• Oral mucosal changes (erythema, lichenoid changes, ulcers, or mucoceles).
• Thrombocytopenia (platelets \< 50,000/uL).
• Abnormal liver function testing defined as alkaline phosphatase, AST, ALT, or total bilirubin \> upper limit of normal (ULN).
• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• David Miklos: lead
• Novartis: collaborator

Study Sites (2)

Stanford University School of Medicine

Stanford, California, 94305, United States

Location

Fred Hutchinson Cancer Research Center (FHCRC)

Seattle, Washington, 98109, United States

Location

Related 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 antibodies. Blood. 2011 Oct 13;118(15):4070-8. doi: 10.1182/blood-2011-03-341693. Epub 2011 Aug 9.

  PMID: 21828142 RESULT

MeSH Terms

Conditions

Graft vs Host Disease

Interventions

Imatinib Mesylate

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Study Officials

• David Miklos, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: September 25, 2008
• First Posted: September 26, 2008
• Study Start: September 1, 2008
• Primary Completion: April 1, 2012
• Study Completion: April 1, 2012
• Last Updated: April 15, 2020

Record last verified: 2020-04

Locations

US (2)