Imatinib and Rituximab in Treating Cutaneous Sclerosis in Patients With Chronic Graft-Versus-Host Disease
A Randomized Phase II Study of Imatinib and Rituximab for Cutaneous Sclerosis After Allogeneic Hematopoietic Cell Transplantation
5 other identifiers
interventional
72
1 country
10
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Mar 2011
Longer than P75 for phase_2
10 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 1, 2011
CompletedStudy Start
First participant enrolled
March 1, 2011
CompletedFirst Posted
Study publicly available on registry
March 7, 2011
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2015
CompletedResults Posted
Study results publicly available
June 15, 2016
CompletedJune 15, 2016
May 1, 2016
3.8 years
March 1, 2011
September 21, 2015
May 10, 2016
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Significant Clinical Response
Assessed by decline in an affected area's skin score as measured with the Vienna Skin Scale (from 4 \[worst\] to 2, 3 to 1, or 2 to 0 \[best\]) 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 where 1 is worst and 7 is best) or of the ankles by one point (in a 1 to 4 scale where 1 is worst and 4 is best) without a concurrent worsening in another area.
6 months
Secondary Outcomes (6)
Patients Who Were Able to Taper Corticosteroids
6 months
Cumulative Incidence of Treatment Failure
6 months
Number of Patients Achieving Improvement in Cutaneous Sclerosis
6 months
Baseline Histopathologic Score in the Two Treatment Arms
Enrollment
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
6 months
- +1 more secondary outcomes
Study Arms (2)
Arm I (enzyme inhibitor)
EXPERIMENTALPatients receive imatinib mesylate PO QD for 6 months in the absence of progression of sclerosis or unacceptable toxicity.
Arm II (monoclonal antibody)
EXPERIMENTALPatients 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.
Interventions
Given IV
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
- +7 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Lee, Stephanielead
- National Cancer Institute (NCI)collaborator
Study Sites (10)
Mayo Clinic in Arizona
Scottsdale, Arizona, 85259, United States
Stanford University Hospitals and Clinics
Stanford, California, 94305, United States
H. Lee Moffitt Cancer Center and Research Institute
Tampa, Florida, 33612, United States
Washington University School of Medicine
St Louis, Missouri, 63110, United States
Roswell Park Cancer Institute
Buffalo, New York, 14263, United States
Weill Cornell Medical College
New York, New York, 10065, United States
University of North Carolina
Chapel Hill, North Carolina, 27599, United States
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232, United States
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, 98109, United States
Froedtert and the Medical College of Wisconsin
Milwaukee, Wisconsin, 53226, United States
Related Publications (1)
Arai S, Pidala J, Pusic I, Chai X, Jaglowski S, Khera N, Palmer J, Chen GL, Jagasia MH, Mayer SA, Wood WA, Green M, Hyun TS, Inamoto Y, Storer BE, Miklos DB, Shulman HM, Martin PJ, Sarantopoulos S, Lee SJ, Flowers ME. A Randomized Phase II Crossover Study of Imatinib or Rituximab for Cutaneous Sclerosis after Hematopoietic Cell Transplantation. Clin Cancer Res. 2016 Jan 15;22(2):319-27. doi: 10.1158/1078-0432.CCR-15-1443. Epub 2015 Sep 16.
PMID: 26378033RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Stephanie J. Lee MD MPH
- Organization
- FHCRC
Study Officials
- PRINCIPAL INVESTIGATOR
Stephanie Lee
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Principal Investigator
Study Record Dates
First Submitted
March 1, 2011
First Posted
March 7, 2011
Study Start
March 1, 2011
Primary Completion
December 1, 2014
Study Completion
December 1, 2015
Last Updated
June 15, 2016
Results First Posted
June 15, 2016
Record last verified: 2016-05
Data Sharing
- IPD Sharing
- Will share
De-identified patient data and samples may be available with the appropriate approvals. Contact the PI for information.