Rituximab in Preventing Acute Graft-Versus-Host Disease in a Donor Stem Cell Transplant for Hematologic Cancer

August 23, 2023 updated by: University of Nebraska

Rituximab For Prevention Of Acute Graft-Versus-Host Disease (GVHD) After Unrelated Donor Allogeneic Hematopoietic Cell Transplantation (HCT)

This phase II trial is studying how well rituximab works in preventing acute graft-versus-host disease (GVHD) in patients undergoing a donor stem cell transplant for hematologic cancer. Giving chemotherapy and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving a monoclonal antibody, rituximab, together with anti-thymocyte globulin, tacrolimus, and mycophenolate mofetil before and after the transplant may stop this from happening

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

PRIMARY OBJECTIVES:

I. To determine the incidence of grade II-IV acute GVHD at day 100 after matched unrelated donor allogeneic hematopoietic cell transplantation (HCT) when incorporating rituximab in the conditioning regimen.

SECONDARY OBJECTIVES:

I. To determine the day 100 transplant related mortality after matched unrelated donor allogeneic HCT when incorporating rituximab in the conditioning regimen.

II. To determine overall survival (OS) and disease-free survival (DFS) after matched unrelated donor allogeneic HCT when incorporating rituximab in the conditioning regimen.

III. To determine the cumulative incidence of infectious complications at day 100 after matched unrelated donor HCT when incorporating rituximab in the conditioning regimen.

IV. To determine the effect of rituximab addition to the conditioning regimen on recovery of T regulatory (T-reg) cells, and to determine the effect of T-cell, including T-reg, number in the stem cell product and at day 30 on the incidence of grade II-IV acute GVHD (aGVHD) and the cumulative infectious complications at day 100.

V. To determine the effect of rituximab addition to the conditioning regimen on antigen presenting myeloid cell recovery, and to determine the effect of dendritic cell subset DC1, DC2 and myeloid-derived suppressor cells (MDSC), number in the stem cell graft and at day +30 on the incidence of acute GVHD grade II-IV and the cumulative incidence of infectious complications at day 100.

OUTLINE:

CONDITIONING REGIMEN: Patients receive one of the following conditioning regimens as per the transplant physician: cyclophosphamide and total-body irradiation (TBI); targeted busulfan and fludarabine; reduced-dose busulfan and fludarabine; or fludarabine and TBI.

GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive rituximab intravenously (IV) on days -6, 1, 8, and 15 and anti-thymocyte globulin IV over 6-8 hours on days -3 to -1. Patients also receive tacrolimus IV continuously and then orally (PO) beginning on day -1 and continuing until day 150 followed by a taper until day 180 and mycophenolate mofetil PO or IV twice daily on days -1 to 60.

TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day 0.

Patients are followed up periodically for 100 days after transplant.

Study Type

Interventional

Enrollment (Actual)

20

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
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center

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

19 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Diagnosis of acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myelogenous leukemia (CML) in accelerated phase or blast crisis, chronic lymphocytic leukemia (CLL), Non-Hodgkin lymphoma (NHL), myelodysplastic syndromes (MDS) (intermediate-2 or high-risk disease by International Pelvic Pain Society [IPPS])
  • Patients with AML, ALL, or MDS scheduled for myeloablative conditioning should have =< 10% blasts in bone marrow or peripheral blood at the start of conditioning
  • Patients with AML, ALL, or CML scheduled for reduced intensity conditioning or non-myeloablative conditioning should be in complete morphologic remission at the start of conditioning (residual disease by flow cytometry or cytogenetics and/or incomplete recovery of neutrophil or platelet count are acceptable)
  • Patients with CLL or NHL scheduled for reduced intensity or non-myeloablative conditioning should have no evidence of bulky disease (> 50% bone marrow involvement or masses > 10 cm) at the start of conditioning
  • Fulfills all pulmonary, cardiac, renal, and hepatic criteria for standard-of-care matched unrelated donor (MUD) allogeneic HCT
  • Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months after stem cell transplantation
  • Adequately matched unrelated donor available
  • Written informed consent; written informed consent of the unrelated donor is required to participate in the optional studies

Exclusion Criteria:

  • Patient or donor infected with human immunodeficiency virus (HIV)
  • Patient or donor with history of hepatitis B or C and/or positive serology consistent with previous hepatitis B or C infection (patients and/or donor who received Hepatitis B vaccination are acceptable)
  • Patient or donor with active hepatitis B or C and/or detectable viral ribonucleic acid (RNA)
  • More than 20,000 circulating CD20+ cells/uL
  • Treatment with rituximab for any reason in the 12 months preceding HCT
  • Patient scheduled for cord blood transplantation
  • Presence of active uncontrolled infection at start of conditioning
  • Presence of active central nervous system (CNS) disease (history of adequately treated CNS disease is acceptable)
  • Presence of uncontrolled psychiatric disorder
  • Patient unable to give informed consent
  • Unrelated donor products received from the Deutsche Knochenmarkspenderdatei (DKMS) Registry are not eligible for the optional study

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: Treatment (Rituximab and allogeneic HCT transplant)

CONDITIONING REGIMEN: Patients receive one of the following conditioning regimens as per the transplant physician: cyclophosphamide and TBI; targeted busulfan and fludarabine; reduced-dose busulfan and fludarabine; or fludarabine and TBI.

GRAFT-VERSUS-HOST DISEASE PROPHYLAXIS: Patients receive rituximab IV on days -6, 1, 8, and 15 and anti-thymocyte globulin IV over 6-8 hours on days -3 to -1. Patients also receive tacrolimus IV continuously and then PO beginning on day -1 and continuing until day 150 followed by a taper until day 180 and mycophenolate mofetil PO or IV twice daily on days -1 to 60.

TRANSPLANTATION: Patients undergo allogeneic hematopoietic stem cell transplantation on day 0.
Other: laboratory biomarker analysis
Correlative studies
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Radiation: total-body irradiation
Undergo TBI
Other Names:
  • TBI
Drug: mycophenolate mofetil
Given IV or PO
Other Names:
  • Cellcept
  • MMF
Drug: busulfan
Given IV
Other Names:
  • BSF
  • BU
  • Misulfan
  • Mitosan
  • Myeloleukon
Drug: anti-thymocyte globulin
Given IV
Other Names:
  • ATGAM
  • ATG
  • Thymoglobulin
  • lymphocyte immune globulin
Drug: rituximab
Given IV
Other Names:
  • Rituxan
  • Mabthera
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • MOAB IDEC-C2B8
Drug: tacrolimus
Given IV
Other Names:
  • Prograf
  • FK 506
Procedure: allogeneic hematopoietic stem cell transplantation
Stem cell transplant
Biological: graft versus host disease prophylaxis/therapy
Undergo graft versus host disease prophylaxis/therapy
Other Names:
  • prophylaxis/therapy, graft versus host disease
  • prophylaxis/therapy, GVHD
Drug: cyclophosphamide
Given PO or IV
Other Names:
  • Cytoxan
  • Endoxan
  • CPM
  • CTX
  • Endoxana
Biological: graft-versus-tumor induction therapy
Undergo graft-versus-tumor induction therapy
Other Names:
  • graft versus host disease induction
  • graft versus tumor induction
Biological: immunosuppressive therapy
Undergo immunosuppressive therapy
Other Names:
  • immunosuppression

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Participants With Grades II-IV Acute GVHD
Time Frame: At day 100
Determined with death as a competing risk. Defined and staged using the 1994 consensus conference modifications of the Glucksberg criteria.
At day 100

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free Survival
Time Frame: From the date of transplant with relapse/progression or death as censored events, up to 2 years
Estimated using Kaplan-Meier estimator.
From the date of transplant with relapse/progression or death as censored events, up to 2 years
Overall Survival
Time Frame: From the date of transplant with death from any cause as a censored event, up to 2 years
Estimated using Kaplan-Meier estimator.
From the date of transplant with death from any cause as a censored event, up to 2 years
Transplant-related Mortality (TRM)
Time Frame: At day 100
Transplant-related mortality (TRM) defined as any mortality after transplantation except mortality from relapsed disease - Reported as a simple percentage.
At day 100

Collaborators and Investigators

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

Sponsor

University of Nebraska

Collaborators

National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Robert Bociek, MD, University of Nebraska

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 (Actual)

December 10, 2009

Primary Completion (Actual)

December 19, 2012

Study Completion (Actual)

October 10, 2017

Study Registration Dates

First Submitted

January 7, 2010

First Submitted That Met QC Criteria

January 7, 2010

First Posted (Estimated)

January 8, 2010

Study Record Updates

Last Update Posted (Estimated)

September 6, 2023

Last Update Submitted That Met QC Criteria

August 23, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0083-09-FB
  • P30CA036727 (U.S. NIH Grant/Contract)
  • NCI-2009-01552 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

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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