Imatinib and Rituximab in Treating Cutaneous Sclerosis in Patients With Chronic Graft-Versus-Host Disease

May 10, 2016 updated by: Lee, Stephanie

A Randomized Phase II Study of Imatinib and Rituximab for Cutaneous Sclerosis After Allogeneic Hematopoietic Cell Transplantation

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
72

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Arizona
      • Scottsdale, Arizona, United States, 85259
        • Mayo Clinic in Arizona
    • California
      • Stanford, California, United States, 94305
        • Stanford University Hospitals and Clinics
    • Florida
      • Tampa, Florida, United States, 33612
        • H. Lee Moffitt Cancer Center and Research Institute
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New York
      • Buffalo, New York, United States, 14263
        • Roswell Park Cancer Institute
      • New York, New York, United States, 10065
        • Weill Cornell Medical College
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt-Ingram Cancer Center
    • Washington
      • Seattle, Washington, United States, 98109
        • Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
    • Wisconsin
      • Milwaukee, Wisconsin, United States, 53226
        • Froedtert and the Medical College of Wisconsin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

2 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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:
  • Gleevec
  • CGP 57148
  • Glivec
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:
  • Rituxan
  • Mabthera
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • MOAB IDEC-C2B8

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Significant Clinical Response
Time Frame: 6 months
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Patients Who Were Able to Taper Corticosteroids
Time Frame: 6 months
Patients who achieved a greater than or equal to 50% reduction in the daily corticosteroid dose at 6mo compared to baseline
6 months
Cumulative Incidence of Treatment Failure
Time Frame: 6 months
Defined as discontinuation of randomized treatment due to chronic GVHD progression or treatment intolerance or no significant clinical response in sclerosis.
6 months
Number of Patients Achieving Improvement in Cutaneous Sclerosis
Time Frame: 6 months
Assessed by decrease of >= 0.2 units (where 0 is best and 3.0 is worst ) in the Scleroderma Health Assessment Questionnaire (SHAQ).
6 months
Baseline Histopathologic Score in the Two Treatment Arms
Time Frame: Enrollment

Instrument: Nash dermal fibrosis grade. Measures extent of sclerosis in skin biopsies by histologic examination. Scale ranges from grade 0-5. Nash grade 5 is most severe fibrosis (0 is better outcome, 5 is worse outcome). No subscales are used in Nash grade. Please see table 1 in the reference for grading of dermal fibrosis.

Nash RA, McSweeney PA, Crofford LJ, Abidi M, Chen CS, Godwin JD, et al. High-dose immunosuppressive therapy and autologous hematopoietic cell transplantation for severe systemic sclerosis: long-term follow-up of the US multicenter pilot study. Blood 2007;110:1388-96.
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
Time Frame: 6 months
Maximum of 10 body areas. Each area can be graded 0 (best) to 4 (worst). Each of those grades requires a percentage of involvement. Improvement is measured by reduction of involvement in any grade and any body area.
6 months
Percentage of CD27+ B Cells in Responders (SCR) and Non-responders
Time Frame: 6 months
%CD27+ B cells
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Lee, Stephanie

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Cancer Institute (NCI)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Stephanie Lee, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 1, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2014

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2015

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 1, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 4, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 7, 2011

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 15, 2016

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 10, 2016

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2343.00 (Other Identifier: Fred Hutchinson Cancer Research Center)
  • P30CA015704 (U.S. NIH Grant/Contract)
  • U54CA163438 (U.S. NIH Grant/Contract)
  • NCI-2011-00098 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
  • RDCRN 6502 (Other Identifier: Rare Diseases Clinical Research Network II)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

De-identified patient data and samples may be available with the appropriate approvals. Contact the PI for information.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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