A Randomized Phase II Study of Imatinib and Rituximab for Cutaneous Sclerosis After Allogeneic Hematopoietic Cell Transplantation
2 Years
N/A
Both
Graft Versus Host Disease, Systemic Scleroderma
Trial Information
A Randomized Phase II Study of Imatinib and Rituximab for Cutaneous Sclerosis After Allogeneic Hematopoietic Cell Transplantation
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(PDGFRA) 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.
Inclusion Criteria:
- Cutaneous sclerosis after hematopoietic cell transplant (HCT) diagnosed no more than
18 months before study enrollment with sclerotic skin, morphea, myofascial
involvement or joint contractures with a score of 2 or greater on the Vienna skin
scale in any area, or a score of 5 or less at the shoulder, elbow or wrist, or a
score of 3 or less at the ankle on the range-of-motion (ROM) assessment
- Stable doses of systemic immunosuppressive medications for a minimum of 4 weeks prior
to the date of consent
- 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
- Known hepatitis B surface antigen positive
- Pregnant, lactating, or planning a pregnancy while in the study
- Distal extremity skin score 3 or higher as the only manifestation of sclerosis
- Treatment of chronic GVHD with either Imatinib or Rituximab, or receipt of Imatinib
or Rituximab within the previous 6 months for any other indication
- 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
- Current treatment with sirolimus (patients may stop sirolimus on the day of
enrollment; if randomized to imatinib, they should wait seven days before starting
the study drug)
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Significant clinical response
Outcome Description:
Assessed by decline in an affected area's skin score as measured with the Vienna Skin Scale (from 4 to 2, 3 to 1, or 2 to 0) without a concurrent increase of two or more points in another area OR by an increase in the range of motion of the shoulders, elbows or wrists by two points (in a 1-7 scale) or of the ankles by one point (in a 1 to 4 scale) without a concurrent worsening in another area.
Outcome Time Frame:
3 and 6 months
Safety Issue:
No
Principal Investigator
Mary Flowers
Investigator Role:
Principal Investigator
Investigator Affiliation:
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Authority:
United States: Food and Drug Administration
Study ID:
2343.00
NCT ID:
NCT01309997
Start Date:
March 2011
Completion Date:
Related Keywords:
- Graft Versus Host Disease
- Systemic Scleroderma
- Imatinib, Rituximab, Chronic Graft-vs-Host Disease
- Scleroderma, Systemic
- Scleroderma, Diffuse
- Graft vs Host Disease
- Sclerosis
Name | Location |
|---|---|
| Roswell Park Cancer Institute | Buffalo, New York 14263 |
| H. Lee Moffitt Cancer Center and Research Institute | Tampa, Florida 33612 |
| Washington University School of Medicine | Saint Louis, Missouri 63110 |
| Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium | Seattle, Washington 98109 |
| Vanderbilt University | Nashville, Tennessee 37232-6305 |
| Froedtert and the Medical College of Wisconsin | Milwaukee, Wisconsin 53226 |
| University of North Carolina at Chapel Hill | Chapel Hill, North Carolina 27599 |
| Weill Cornell Medical College | New York, New York 10021 |
| Stanford University Hospitals and Clinics | Stanford, California 94305 |
| Dana-Farber Harvard Cancer Center | Boston, Massachusetts 02115 |
| Mayo Clinic--Scottsdale | Scottsdale, Arizona 85054 |
| University of Minnesota Medical Center-Fairview-Riverside | Minneapolis, Minnesota 55454-1493 |
