Trial record 1 of 42 for:    cutaneous sclerosis
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Imatinib and Rituximab in Treating Cutaneous Sclerosis in Patients With Chronic Graft-Versus-Host Disease

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Lee, Stephanie, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier:
NCT01309997
First received: March 1, 2011
Last updated: July 29, 2014
Last verified: July 2014
  Purpose

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.


Condition Intervention Phase
Graft Versus Host Disease
Systemic Scleroderma
Drug: imatinib mesylate
Biological: rituximab
Other: laboratory biomarker analysis
Other: questionnaire administration
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized Phase II Study of Imatinib and Rituximab for Cutaneous Sclerosis After Allogeneic Hematopoietic Cell Transplantation

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Significant clinical response [ Time Frame: 3 and 6 months ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Proportion of patients achieving a greater than or equal to 50% reduction in the daily corticosteroid dose [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Cumulative incidence of treatment failure [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Defined as discontinuation of randomized treatment due to chronic GVHD progression or treatment intolerance or no significant clinical response in sclerosis.

  • Number of patients achieving improvement in cutaneous sclerosis [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Assessed by decrease of >= 0.2 units in the Scleroderma Health Assessment Questionnaire (SHAQ).

  • Correlation of blood and skin biomarker profile with each therapeutic agent and clinical response [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

Estimated Enrollment: 74
Study Start Date: March 2011
Estimated Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (enzyme inhibitor)
Patients receive imatinib mesylate PO QD for 6 months in the absence of progression of sclerosis or unacceptable toxicity.
Drug: imatinib mesylate
Given PO
Other Names:
  • CGP 57148
  • Gleevec
  • Glivec
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies
Experimental: Arm II (monoclonal antibody)
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.
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Other: laboratory biomarker analysis
Correlative studies
Other: questionnaire administration
Ancillary studies

Detailed 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.

  Eligibility

Ages Eligible for Study:   2 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 =< 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01309997

Locations
United States, Arizona
Mayo Clinic in Arizona
Scottsdale, Arizona, United States, 85259
United States, California
Stanford University Hospitals and Clinics
Stanford, California, United States, 94305
United States, Florida
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, United States, 33612
United States, Missouri
Washington University School of Medicine
Saint Louis, Missouri, United States, 63110
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10065
Weill Cornell Medical College
New York, New York, United States, 10065
United States, North Carolina
University of North Carolina
Chapel Hill, North Carolina, United States, 27599
United States, Ohio
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center
Cleveland, Ohio, United States, 44195
United States, Tennessee
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, United States, 37232
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
United States, Wisconsin
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, United States, 53226
Sponsors and Collaborators
Lee, Stephanie
Investigators
Principal Investigator: Stephanie Lee Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Lee, Stephanie, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
ClinicalTrials.gov Identifier: NCT01309997     History of Changes
Other Study ID Numbers: 2343.00, NCI-2011-00098, RDCRN 6502, RDCRN 6502, 2343.00, U54CA163438, P30CA015704
Study First Received: March 1, 2011
Last Updated: July 29, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Fred Hutchinson Cancer Research Center:
Imatinib
Rituximab
Chronic Graft-vs-Host Disease

Additional relevant MeSH terms:
Graft vs Host Disease
Scleroderma, Systemic
Scleroderma, Diffuse
Immune System Diseases
Connective Tissue Diseases
Skin Diseases
Rituximab
Imatinib
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on September 16, 2014