Rituximab for Prevention of Chronic GVHD

February 3, 2014 updated by: Corey S. Cutler, MD, MPH, Dana-Farber Cancer Institute

A Phase II Trial of Prophylactic Rituximab Therapy for Prevention of Chronic Graft-vs.-Host Disease After Allogeneic Stem Cell Transplantation

The purpose of this trial is to determine if administration of rituximab after allogeneic stem cell transplantation can reduce the incidence of chronic GVHD. Chronic GVHD is a medical condition that can occur after bone marrow or stem cells are transplanted form one individual to another. After the transplant, the donor immune system may recognize the recipient body as foreign and may attempt to "reject" the body. Rituximab is a drug that interferes with the immune system function by specifically targeting B cells and killing them.

Study Overview

Status

Completed

Conditions

Hematological Malignancies

Intervention / Treatment

Detailed Description

Study Design: The study is designed as a Phase II, open label trial of Rituximab as chronic GVHD prophylaxis after HLA-matched, related or unrelated peripheral blood stem cell transplantation after ablative or non-ablative conditioning.

Primary Objective: To determine the incidence of clinically extensive chronic GVHD at one and two years after allogeneic stem cell transplantation after a single dose of Rituximab administered at 100 days, 6 months, 9 months and 1 year from transplantation as chronic GVHD prophylaxis.

Secondary Objectives: To determine the incidence of adverse hematological events, the incidence of infectious complications, the rate of malignant relapse, and the effects on donor hematopoietic chimerism after Rituximab administration.

Eligibility Criteria: Eligible patients will be 18 years of age or greater and will have undergone a non-myeloablative or fully ablative transplantation from an HLA-matched (6/6 loci) or single antigen/allele mismatched (5/6) donor approximately 100 days ago. Adequate performance status and organ function will be confirmed prior to enrollment. No ongoing infection or acute GVHD will be present at the time of enrollment. Evidence of sustained donor chimerism will be confirmed prior to study entry.

Treatment Description: Chronic GVHD prophylaxis will consist of Rituximab 375 mg/m2 administered 100 days, 6, 9 and 12 months after transplantation.

Accrual Objective: 68 patients will be accrued over 12 months.

Study Duration: Patients will be evaluated for two years after the time of transplantation for evaluation of the primary and secondary endpoints. Subjects will be followed longitudinally after completion of the study period for determination of clinical status.

Study Type

Interventional

Enrollment (Actual)

Phase

Phase 2
Phase 1

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
- Massachusetts
  - Boston, Massachusetts, United States, 02115
    - Dana-Farber Cancer Institute

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

Genders Eligible for Study

All

Description

Inclusion Criteria:

Patients who have undergone either ablative or non-myeloablative allogeneic stem cell transplantation
Peripheral blood stem cells must have been used as the stem cell source
Patients must have received transplantation from donors who are identical at 6 HLA loci, or mismatched at no more than 1 locus.
Patients who have undergone a non-myeloablative stem cell transplant must have > 80% donor hematopoiesis within 30 days of study enrollment
18 years of age or older
Performance Status 0-2
Life expectancy of > 100 days
Subjects with CLL are eligible, if there is no more than 20% residual leukemia in the bone marrow at the time of study entry

Exclusion Criteria:

Evidence of relapsed or residual malignancy within 30 days of trial entry
Highly aggressive B cell malignancy, such as Burkitt's lymphoma or Burkitt's-like lymphoma
Allogeneic stem cell transplantation using a single or multiple umbilical cord blood units or using bone marrow
Evidence of any active uncontrolled infection, or evidence of natural exposure to Hepatitis B, Hepatitis C or HIV
Evidence of ongoing gastrointestinal or hepatic acute GVHD, or evidence of greater than ongoing Stage I cutaneous acute GVHD
GVHD with chronic features diagnosed prior to day +100 or prior to enrollment
Participation in a clinical trial evaluating another preventative strategy for chronic GVHD, or ongoing participation in a clinical trial for therapy of acute GVHD
No Donor Lymphocyte Infusion (DLI) prior to day 100 and not plans for a DLI in the upcoming 30 days
Heart failure uncontrolled by medications
Pregnancy or lactation

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: Prevention
Allocation: Non-Randomized
Interventional Model: Single Group Assignment
Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Incidence of Clinician-diagnosed Chronic GVHD at One and Two Years Time Frame: by 1 and 2 years after peripheral blood stem cell (PBSC) infusion	by 1 and 2 years after peripheral blood stem cell (PBSC) infusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Grade 3 or Higher Infectious Complications Time Frame: by 1 and 2 years after peripheral blood stem cell (PBSC) infusion		by 1 and 2 years after peripheral blood stem cell (PBSC) infusion
Incidence of Relapse or Progression of Disease Time Frame: by 4 years after peripheral blood stem cell (PBSC) infusion	Percentage of participants with relapsed disease by year 4 post transplant.	by 4 years after peripheral blood stem cell (PBSC) infusion
Incidence of Adverse Hematological Events Time Frame: by 18 months after peripheral blood stem (PBSC) infusion	White blood cell decrease, neutrophil cell count decrease, or platelet cell decrease considered possibly or probably related to therapy with rituximab.	by 18 months after peripheral blood stem (PBSC) infusion

Collaborators and Investigators

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

Sponsor

Dana-Farber Cancer Institute

Collaborators

Genentech, Inc.

Biogen

Investigators

Principal Investigator: Corey Cutler, Dana-Farber Cancer Institute

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

Cutler C, Kim HT, Bindra B, Sarantopoulos S, Ho VT, Chen YB, Rosenblatt J, McDonough S, Watanaboonyongcharoen P, Armand P, Koreth J, Glotzbecker B, Alyea E, Blazar BR, Soiffer RJ, Ritz J, Antin JH. Rituximab prophylaxis prevents corticosteroid-requiring chronic GVHD after allogeneic peripheral blood stem cell transplantation: results of a phase 2 trial. Blood. 2013 Aug 22;122(8):1510-7. doi: 10.1182/blood-2013-04-495895. Epub 2013 Jul 16.

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

September 1, 2006

Primary Completion (Actual)

August 1, 2012

Study Completion (Actual)