Phase 2
N=72
Imatinib and Rituximab in Treating Cutaneous Sclerosis in Patients With Chronic Graft-Versus-Host Disease
Graft Versus Host Disease · Systemic Scleroderma
Bottom Line
View on ClinicalTrials.gov: NCT01309997 ↗Enrolled (actual)
72
Serious AEs
56.1%
Results posted
Jun 2016
Primary outcome: Primary: Significant Clinical Response — 9; 10 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- imatinib mesylate (Drug); rituximab (Biological)
- Age
- Pediatric, Adult, Older Adult · 2+ yrs
- Sex
- All
- Sponsor
- Lee, Stephanie
- Primary completion
- Dec 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Significant Clinical Response |
9; 10 | — |
| SECONDARY Patients Who Were Able to Taper Corticosteroids |
7; 9 | — |
| SECONDARY Cumulative Incidence of Treatment Failure |
24; 26 | — |
| SECONDARY Number of Patients Achieving Improvement in Cutaneous Sclerosis |
2; 9 | — |
| SECONDARY Baseline Histopathologic Score in the Two Treatment Arms |
2; 2 | — |
| SECONDARY Patients With Any Percentage Decline in Any Grade of Sclerosis Without Increase in Percentage of Higher Grades of Sclerosis in Other Areas on the Vienna Skin Scale |
14; 9 | — |
| SECONDARY Percentage of CD27+ B Cells in Responders (SCR) and Non-responders |
10; 4.3; 14.2; 17.1 | 0.01 sig |
Summary
This randomized phase II trial is evaluating how well imatinib mesylate works compared to rituximab in treating cutaneous sclerosis in patients with chronic graft- versus-host disease (GVHD). Both imatinib and rituximab have been reported to decrease skin thickening and improve skin and joint flexibility in people with cutaneous sclerosis due to chronic GVHD.
Eligibility Criteria
Inclusion Criteria
- Diagnosis within the past 18 months of cutaneous sclerosis after hematopoietic cell transplant (HCT) with sclerotic skin, morphea, myofascial involvement or joint contractures; must have a score of 2 or greater on the Vienna skin scale in any area, or a range-of-motion (ROM) score of 5 or less at the shoulder, elbow or wrist, or 3 or less at the ankle
- No medication added for the treatment of graft versus host disease (GVHD) within the past 4 weeks
- Receiving corticosteroids at a dose greater than required for treatment of adrenal insufficiency, unless the physician documents why steroids are contraindicated
- Age 2-99 years
- Karnofsky performance status >= 60% at enrollment
- All females of childbearing potential must have a negative serum or urine pregnancy test = 1.5x upper limit of normal (ULN)
- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 x ULN
- Renal insufficiency (serum creatinine > 2.0 mg/dl)
- Platelets < 30, 000/ul or absolute neutrophil count < 1500/ul
- Known hypersensitivity to rituximab or other anti-B cell antibodies
- Known imatinib intolerance or allergy
- Evidence of any active viral, bacterial, or fungal infection that is progressive despite appropriate treatment
- Hepatitis B surface antigen positive
- Hepatitis B core antibody positive, unless hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is undetectable
- Hepatitis C antibody positive, unless hepatitis C virus (HCV) ribonucleic acid (RNA) is undetectable
- Pregnant, lactating, or planning a pregnancy while in the study
- Distal leg skin score 3 or higher as the only manifestation of sclerosis
- Prior treatment of chronic GVHD with imatinib, rituximab, or any other monoclonal B-cell antibody (e.g. ofatumumab)
- Receipt of imatinib within the previous 6 months for any indication
- Receipt of any monoclonal B-cell antibody (e.g. rituximab, ofatumumab) within the previous 12 months for any indication
- Treatment with anti-B-cell cellular therapy (e.g. chimeric antigen-receptor-engineered cells) at any time after transplant
- Current treatment with extracorporeal photopheresis (ECP) at the time of enrollment
- History of psychiatric disorder that would interfere with normal participation in this study
- Inability or unwillingness of subject and/or parent guardian to provide informed consent or comply with study protocol
- Use of non-FDA approved drugs within 4 weeks of participation
- Patient with any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with the study requirements
- Patients with uncontrolled substance abuse
Data sourced from ClinicalTrials.gov (NCT01309997). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.