Rituximab for the Primary Treatment of Denovo Extensive Chronic Graft Versus Host Disease (GVHD)

March 22, 2016 updated by: Northside Hospital, Inc.

Phase II Trial Evaluating the Safety and Efficacy of Rituximab as Primary Treatment for Extensive Chronic Graft Versus Host Disease

Rituximab is an attractive agent to bring to the upfront treatment of chronic graft-versus-host disease (cGVHD) due to its favorable toxicity profile, its proven efficacy in the treatment of steroid-refractory cGVHD, and its ability to serve as a steroid sparing agent in other autoimmune diseases. The investigators hope to demonstrate that Rituximab has significant activity in cGVHD when utilized early in the course of the process. In addition, the investigators hope to show that the early use of Rituximab may allow for the earlier discontinuation of immunosuppression while obviating the need for long courses of systemic corticosteroids, which should translate into reduced treatment-related morbidity and mortality associated with cGVHD.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Although allogeneic hematopoietic stem cell transplantation (HSCT) remains an important curative therapy for many patients with hematological malignancies, treatment-related morbidity and mortality continue to be a major challenge. Chronic GVHD remains a major complication following allogeneic HSCT, with more than half of patients being affected. Although cGVHD has been associated with decreased relapse risk due to the well documented graft-versus-malignancy effect, it is also associated with significant adverse consequences in terms of morbidity, mortality, quality-of-life, and treatment costs associated with HSCT.

Rituximab has been investigated in a small number of patients with refractory cGVHD using the standard regimen of 375 mg/m2/week for 4 weeks. Ratanatharathorn et al. documented a sustained response in four of eight patients with steroid-refractory cGVHD with diffuse or localized sclerodermatous manifestations. Similarly, Canninga-vanDijk et al. and Okamoto et al. observed cases with clinical, laboratory and histological improvement after Rituximab treatment. Cutler et al. reported the results of their phase I-II study with Rituximab in 21 patients with steroid-refractory cGVHD. Treatment was well tolerated, and toxicity limited to infectious events, without any hematological toxicities and only a significant reduction in circulating immunoglobulins documented after therapy. Objective responses were documented in 70% of patients (including 10% complete response) primarily for those with skin and musculoskeletal involvement, allowing tapering, and in some cases withdrawing, of previous immunosuppressant therapy. A correlation between clinical response and decrease in the titre of antibodies against Y chromosome-encoded minor HLA antigens was shown. The results of these preliminary studies highlight the potential therapeutic activity of Rituximab on some cGVHD manifestations and a particularly high efficacy for skin involvement, including scleroderma. Recently, Zaja et al. confirmed the activity of Rituximab in refractory cGVHD in a larger series of 38 patients. Treatment was generally well tolerated and nearly 60% and 50% of patients had a clinical improvement of their skin and mouth manifestations, respectively. The median time-to-response was nearly 2 months and in some cases responses were durable. Responses were also detectable in some patients with eye, liver, lung, gut and joint involvement, allowing reduction and/or suspension of previous baseline immunosuppressive therapy in a significant number of patients

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • 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
    • Georgia
      • Atlanta, Georgia, United States, 30342
        • Northside Hospital

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

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • First episode of extensive chronic GvHD, without residual or concurrent acute GvHD.
  • Age 18 - 75
  • Any primary diagnosis requiring treatment by allogeneic HSCT
  • Recipient of an allogeneic stem cell transplant (bone marrow, peripheral blood stem cell, or cord blood) from a related or unrelated donor, minimum 80 days ago
  • Conditioning regimen: Myeloablative or non-myeloablative
  • Patient gives written informed consent

Exclusion Criteria:

  • Creatinine > 2.0 mg/dl
  • Uncontrolled, active infection
  • Recurrent or progressive malignancy
  • Anticipated life expectancy of less than 1 year
  • Pregnant or breast feeding
  • Contraindications to administration of the study intervention or known inability of the patient to tolerate the study intervention
  • Patients with perceived fixed, irreversible defects (pulmonary involvement, contractures, etc.) which would not be expected to improve with the study intervention
  • Residual or concurrent acute GVHD

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: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rituxan
All patients receive Rituximab 375 mg/m2/dose x 4 weekly doses on days 1, 8, 15 and 22 and then at 3, 6, 9 and 12 months.
Drug: Rituximab
Rituximab 375 mg/m2/dose x 4 weekly doses on days 1, 8, 15 and 22 and then at 3, 6, 9 and 12 months.
Other Names:
  • Rituxan

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Rate of Complete Response of cGVHD to Treatment.
Time Frame: 2 years
2 years
Rate of Overall Response of cGVHD to Treatment
Time Frame: 2 years
2 years
Rate of Partial Response of cGVHD to Treatment
Time Frame: 2 years
2 years

Secondary Outcome Measures

Outcome Measure
Time Frame
Requirement for Systemic Corticosteroid Use
Time Frame: 2 years
2 years
Time to Immunosuppression Withdrawal
Time Frame: 2 years
2 years
Incidence of Overall Survival
Time Frame: 2 years
2 years
Duration of Systemic Corticosteroid Use
Time Frame: 2 years
2 years
Incidence of Disease-free Survival
Time Frame: 2 years
2 years
Incidence of Non-relapse Mortality
Time Frame: 2 years
2 years

Collaborators and Investigators

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

Sponsor

Northside Hospital, Inc.

Collaborators

Blood and Marrow Transplant Group of Georgia

Investigators

  • Principal Investigator: Scott R Solomon, MD, Blood and Marrow Transplant Group of Georgia

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

April 1, 2011

Primary Completion (Actual)

January 1, 2014

Study Completion (Actual)

July 1, 2015

Study Registration Dates

First Submitted

July 12, 2010

First Submitted That Met QC Criteria

July 12, 2010

First Posted (Estimate)

July 13, 2010

Study Record Updates

Last Update Posted (Estimate)

April 20, 2016

Last Update Submitted That Met QC Criteria

March 22, 2016

Last Verified

January 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NSH 893

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

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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