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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Blood and Marrow Transplant Group of Georgia
Information provided by (Responsible Party):
Northside Hospital, Inc.
ClinicalTrials.gov Identifier:
NCT01161628
First received: July 12, 2010
Last updated: April 28, 2014
Last verified: April 2014
  Purpose

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 Intervention Phase
Chronic Graft-versus-host Disease
Drug: Rituximab
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Northside Hospital, Inc.:

Primary Outcome Measures:
  • To estimate the rate of complete, partial and overall response of cGVHD to treatment. [ Time Frame: 2 years ] [ Designated as safety issue: Yes ]
    We will evaluate patients at 1, 2, 3, 6, 9, 12, 18 and 24 months from the start of treatment.


Secondary Outcome Measures:
  • To estimate the requirement for and duration of systemic corticosteroids [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Steroids can be added to the treatment regimen if cGVHD progresses after 2 weeks of therapy and shows no improvement after 5 weeks. It a patient responds to steroids, they will be tapered every 4 days and should be discontinued in </= 4 weeks.

  • Estimate the time to immunosuppression withdrawal [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    We will evaluate patients at 1, 2, 3, 6, 9, 12, 18 and 24 months from the start of treatment. Steroids can be added to the treatment regimen if cGVHD progresses after 2 weeks of therapy and shows no improvement after 5 weeks. It a patient responds to steroids, they will be tapered every 4 days and should be discontinued in </= 4 weeks.

  • Estimate incidence of non-relapse mortality, disease-free and overall survival [ Time Frame: 2 years ] [ Designated as safety issue: No ]
    Patients will be evaluated at 1, 2, 3, 6, 9, 12, 18 and 24 months after the start of treatment.


Estimated Enrollment: 25
Study Start Date: April 2011
Estimated Study Completion Date: January 2016
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Rituxan
all patients will receive Rituxan for the treatment of newly diagnosed chronic GVHD
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

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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT01161628

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

Publications:

Responsible Party: Northside Hospital, Inc.
ClinicalTrials.gov Identifier: NCT01161628     History of Changes
Other Study ID Numbers: NSH 893
Study First Received: July 12, 2010
Last Updated: April 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Northside Hospital, Inc.:
Chronic Graft versus Host Disease
allogeneic stem cell transplant

Additional relevant MeSH terms:
Graft vs Host Disease
Immune System Diseases
Rituximab
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 26, 2014