Brief Title
Rituximab in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer
Official Title
RITUXIMAB FOR PREVENTION OF ACUTE GRAFT-VERSUS-HOST DISEASE (GVHD) AFTER UNRELATED DONOR ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (HCT)
Brief Summary
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
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
Number of Participants With Grades II-IV Acute GVHD
Secondary Outcome
Event-free Survival
Condition
Accelerated Phase Chronic Myelogenous Leukemia
Intervention
rituximab
Study Arms / Comparison Groups
Treatment (Rituximab and allogeneic HCT transplant)
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
20
Start Date
December 2009
Completion Date
July 2014
Primary Completion Date
October 8, 2012
Eligibility Criteria
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
Gender
All
Ages
19 Years - 75 Years
Accepts Healthy Volunteers
No
Contacts
Robert Bociek, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01044745
Organization ID
083-09
Secondary IDs
NCI-2009-01552
Responsible Party
Principal Investigator
Study Sponsor
University of Nebraska
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Robert Bociek, Principal Investigator, University of Nebraska
Verification Date
February 2019