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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01161628
Recruitment Status : Completed
First Posted : July 13, 2010
Results First Posted : February 24, 2016
Last Update Posted : April 20, 2016
Blood and Marrow Transplant Group of Georgia
Information provided by (Responsible Party):
Northside Hospital, Inc.

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Chronic Graft-versus-host Disease Drug: Rituximab Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Trial Evaluating the Safety and Efficacy of Rituximab as Primary Treatment for Extensive Chronic Graft Versus Host Disease
Study Start Date : April 2011
Actual Primary Completion Date : January 2014
Actual Study Completion Date : July 2015

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 Name: Rituxan

Primary Outcome Measures :
  1. Rate of Complete Response of cGVHD to Treatment. [ Time Frame: 2 years ]
  2. Rate of Overall Response of cGVHD to Treatment [ Time Frame: 2 years ]
  3. Rate of Partial Response of cGVHD to Treatment [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Requirement for Systemic Corticosteroid Use [ Time Frame: 2 years ]
  2. Time to Immunosuppression Withdrawal [ Time Frame: 2 years ]
  3. Incidence of Overall Survival [ Time Frame: 2 years ]
  4. Duration of Systemic Corticosteroid Use [ Time Frame: 2 years ]
  5. Incidence of Disease-free Survival [ Time Frame: 2 years ]
  6. Incidence of Non-relapse Mortality [ Time Frame: 2 years ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01161628

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United States, Georgia
Northside Hospital
Atlanta, Georgia, United States, 30342
Sponsors and Collaborators
Northside Hospital, Inc.
Blood and Marrow Transplant Group of Georgia
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Principal Investigator: Scott R Solomon, MD Blood and Marrow Transplant Group of Georgia

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Responsible Party: Northside Hospital, Inc. Identifier: NCT01161628    
Other Study ID Numbers: NSH 893
First Posted: July 13, 2010    Key Record Dates
Results First Posted: February 24, 2016
Last Update Posted: April 20, 2016
Last Verified: January 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Keywords provided by Northside Hospital, Inc.:
Chronic Graft versus Host Disease
allogeneic stem cell transplant
Additional relevant MeSH terms:
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Graft vs Host Disease
Immune System Diseases
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents