This trial is active, not recruiting.

Conditions graft versus host disease, systemic scleroderma
Treatments imatinib mesylate, rituximab, laboratory biomarker analysis, questionnaire administration
Phase phase 2
Target CD20
Sponsor Lee, Stephanie
Collaborator National Cancer Institute (NCI)
Start date March 2011
End date December 2014
Trial size 74 participants
Trial identifier NCT01309997, 2343.00, NCI-2011-00098, P30CA015704, RDCRN 6502, U54CA163438


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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model crossover assignment
Masking open label
Primary purpose treatment
Patients receive imatinib mesylate PO QD for 6 months in the absence of progression of sclerosis or unacceptable toxicity.
imatinib mesylate CGP 57148
Given PO
laboratory biomarker analysis
Correlative studies
questionnaire administration
Ancillary studies
Patients receive rituximab IV on days 1, 8, 15, and 22. A second treatment cycle is repeated at 3 months for a total of 8 doses of rituximab in the absence of progression of sclerosis or unacceptable toxicity.
rituximab IDEC-C2B8
Given IV
laboratory biomarker analysis
Correlative studies
questionnaire administration
Ancillary studies

Primary Outcomes

Significant clinical response
time frame: 3 and 6 months

Secondary Outcomes

Proportion of patients achieving a greater than or equal to 50% reduction in the daily corticosteroid dose
time frame: 6 months
Cumulative incidence of treatment failure
time frame: 6 months
Number of patients achieving improvement in cutaneous sclerosis
time frame: 6 months
Correlation of blood and skin biomarker profile with each therapeutic agent and clinical response
time frame: 6 months
Proportion of subjects 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
time frame: 6 months

Eligibility Criteria

Male or female participants at least 2 years old.

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 =< 7 days prior to starting study therapy - All females of childbearing potential must agree to use a form of Food and Drug Administration (FDA) approved contraception from enrollment to one month after study treatment ends - Subject has the ability to understand and willingness to sign a written informed consent document Exclusion Criteria: - Total bilirubin > 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

Additional Information

Official title A Randomized Phase II Study of Imatinib and Rituximab for Cutaneous Sclerosis After Allogeneic Hematopoietic Cell Transplantation
Principal investigator Stephanie Lee
Description PRIMARY OBJECTIVES: I. To determine the best clinical response rate of cutaneous sclerosis (skin and/or fascial thickening) after 6 months of initial therapy with either imatinib (imatinib mesylate) or rituximab. SECONDARY OBJECTIVES: I. To determine the best response at either the 3 or 6 month assessment. II. To determine the response rate at the 3 month assessment. III. To determine the proportion of subjects who are able to taper corticosteroid after 6 months of imatinib or rituximab therapy. IV. To determine the incidence of treatment failure to initial treatment with either imatinib or rituximab. V. To evaluate if the Scleroderma Health Assessment Questionnaire (SHAQ) findings correlate with severity of cutaneous sclerosis clinical findings and response to study treatment. VI. To correlate the detection of antibody against platelet derived growth factor receptor alpha (PDGFR A) with clinical response. VII. To correlate change in B cell relevant parameters from baseline to 6 months or early crossover (antibody levels, skin collagen expression, B cell subsets) with therapeutic agent and best clinical response while on initial treatment. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients receive imatinib mesylate by mouth (PO) once daily (QD) for 6 months in the absence of progression of sclerosis or unacceptable toxicity. Subjects with a significant clinical response will continue to receive study drug for an additional 6 months. ARM II: Patients receive rituximab intravenously (IV) on days 1, 8, 15, and 22 (first cycle). A second cycle of treatment with rituximab is repeated at 3 months for a total of 8 doses of rituximab in the absence of progression of sclerosis or unacceptable toxicity. Patients with progression, treatment intolerance at any time up to 6 months, or no clinical response at 6 months will crossover to the other treatment arm.
Trial information was received from ClinicalTrials.gov and was last updated in August 2015.
Information provided to ClinicalTrials.gov by Fred Hutchinson Cancer Research Center.