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

NCT ID: NCT00760981

Last Updated: 2020-04-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-30
• Study Completion Date: 2012-04-30

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Imatinib

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

Group Type: EXPERIMENTAL

Imatinib

Intervention Type: DRUG

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

Interventions

Imatinib

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

Intervention Type: DRUG

Other Intervention Names

Gleevec

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis

INDUSTRY

Sponsor Role: collaborator

David Miklos

OTHER

Sponsor Role: lead

Responsible Party

David Miklos

Assistant Professor of Medicine

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

David Miklos, MD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

Stanford University School of Medicine

Stanford, California, United States

Fred Hutchinson Cancer Research Center (FHCRC)

Seattle, Washington, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 21828142 (View on PubMed)

Other Identifiers

14821

Identifier Type: OTHER

Identifier Source: secondary_id

BMT195

Identifier Type: OTHER

Identifier Source: secondary_id

IRB-14821

Identifier Type: -

Identifier Source: org_study_id