Overview

This trial is active, not recruiting.

Conditions accelerated phase chronic myelogenous leukemia, adult acute lymphoblastic leukemia in remission, adult acute myeloid leukemia in remission, adult nasal type extranodal nk/t-cell lymphoma, blastic phase chronic myelogenous leukemia, contiguous stage ii adult burkitt lymphoma, contiguous stage ii adult diffuse large cell lymphoma, contiguous stage ii adult diffuse mixed cell lymphoma, contiguous stage ii adult diffuse small cleaved cell lymphoma, contiguous stage ii adult immunoblastic large cell lymphoma, contiguous stage ii adult lymphoblastic lymphoma, contiguous stage ii grade 1 follicular lymphoma, contiguous stage ii grade 2 follicular lymphoma, contiguous stage ii grade 3 follicular lymphoma, contiguous stage ii mantle cell lymphoma, contiguous stage ii marginal zone lymphoma, contiguous stage ii small lymphocytic lymphoma, de novo myelodysplastic syndromes, extranodal marginal zone b-cell lymphoma of mucosa-associated lymphoid tissue, graft versus host disease, nodal marginal zone b-cell lymphoma, noncontiguous stage ii adult burkitt lymphoma, noncontiguous stage ii adult diffuse large cell lymphoma, noncontiguous stage ii adult diffuse mixed cell lymphoma, noncontiguous stage ii adult diffuse small cleaved cell lymphoma, noncontiguous stage ii adult immunoblastic large cell lymphoma, noncontiguous stage ii adult lymphoblastic lymphoma, noncontiguous stage ii grade 1 follicular lymphoma, noncontiguous stage ii grade 2 follicular lymphoma, noncontiguous stage ii grade 3 follicular lymphoma, noncontiguous stage ii mantle cell lymphoma, noncontiguous stage ii marginal zone lymphoma, noncontiguous stage ii small lymphocytic lymphoma, previously treated myelodysplastic syndromes, recurrent adult acute lymphoblastic leukemia, recurrent adult acute myeloid leukemia, recurrent adult burkitt lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult grade iii lymphomatoid granulomatosis, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult t-cell leukemia/lymphoma, recurrent cutaneous t-cell non-hodgkin lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent mycosis fungoides/sezary syndrome, recurrent small lymphocytic lymphoma, refractory chronic lymphocytic leukemia, relapsing chronic myelogenous leukemia, secondary myelodysplastic syndromes, splenic marginal zone lymphoma, stage i adult burkitt lymphoma, stage i adult diffuse large cell lymphoma, stage i adult diffuse mixed cell lymphoma, stage i adult diffuse small cleaved cell lymphoma, stage i adult immunoblastic large cell lymphoma, stage i adult lymphoblastic lymphoma, stage i adult t-cell leukemia/lymphoma, stage i chronic lymphocytic leukemia, stage i cutaneous t-cell non-hodgkin lymphoma, stage i grade 1 follicular lymphoma, stage i grade 2 follicular lymphoma, stage i grade 3 follicular lymphoma, stage i mantle cell lymphoma, stage i marginal zone lymphoma, stage i mycosis fungoides/sezary syndrome, stage i small lymphocytic lymphoma, stage ii adult t-cell leukemia/lymphoma, stage ii chronic lymphocytic leukemia, stage ii cutaneous t-cell non-hodgkin lymphoma, stage ii mycosis fungoides/sezary syndrome, stage iii adult burkitt lymphoma, stage iii adult diffuse large cell lymphoma, stage iii adult diffuse mixed cell lymphoma, stage iii adult diffuse small cleaved cell lymphoma, stage iii adult immunoblastic large cell lymphoma, stage iii adult lymphoblastic lymphoma, stage iii adult t-cell leukemia/lymphoma, stage iii chronic lymphocytic leukemia, stage iii cutaneous t-cell non-hodgkin lymphoma, stage iii grade 1 follicular lymphoma, stage iii grade 2 follicular lymphoma, stage iii grade 3 follicular lymphoma, stage iii mantle cell lymphoma, stage iii marginal zone lymphoma, stage iii mycosis fungoides/sezary syndrome, stage iii small lymphocytic lymphoma, stage iv adult burkitt lymphoma, stage iv adult diffuse large cell lymphoma, stage iv adult diffuse mixed cell lymphoma, stage iv adult diffuse small cleaved cell lymphoma, stage iv adult immunoblastic large cell lymphoma, stage iv adult lymphoblastic lymphoma, stage iv adult t-cell leukemia/lymphoma, stage iv chronic lymphocytic leukemia, stage iv cutaneous t-cell non-hodgkin lymphoma, stage iv grade 1 follicular lymphoma, stage iv grade 2 follicular lymphoma, stage iv grade 3 follicular lymphoma, stage iv mantle cell lymphoma, stage iv marginal zone lymphoma, stage iv mycosis fungoides/sezary syndrome, stage iv small lymphocytic lymphoma, untreated adult acute lymphoblastic leukemia, untreated adult acute myeloid leukemia, waldenström macroglobulinemia
Treatments rituximab, mycophenolate mofetil, tacrolimus, anti-thymocyte globulin, allogeneic hematopoietic stem cell transplantation, laboratory biomarker analysis, graft versus host disease prophylaxis/therapy, cyclophosphamide, fludarabine phosphate, busulfan, total-body irradiation, graft-versus-tumor induction therapy, immunosuppressive therapy
Phase phase 2
Target CD20
Sponsor University of Nebraska
Collaborator National Cancer Institute (NCI)
Start date December 2009
End date December 2014
Trial size 50 participants
Trial identifier NCT01044745, 083-09, NCI-2009-01552, P30CA036727

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

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
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.
rituximab IDEC-C2B8
Given IV
mycophenolate mofetil Cellcept
Given IV or PO
tacrolimus FK 506
Given IV
anti-thymocyte globulin ATG
Given IV
allogeneic hematopoietic stem cell transplantation
Stem cell transplant
laboratory biomarker analysis
Correlative studies
graft versus host disease prophylaxis/therapy prophylaxis/therapy, graft versus host disease
Undergo graft versus host disease prophylaxis/therapy
cyclophosphamide CPM
Given PO or IV
fludarabine phosphate 2-F-ara-AMP
Given IV
busulfan BSF
Given IV
total-body irradiation TBI
Undergo TBI
graft-versus-tumor induction therapy graft versus host disease induction
Undergo graft-versus-tumor induction therapy
immunosuppressive therapy immunosuppression
Undergo immunosuppressive therapy

Primary Outcomes

Measure
Incidence of grades II-IV acute GVHD
time frame: At day 100

Secondary Outcomes

Measure
Event-free survival
time frame: From the date of transplant with relapse/progression or death as censored events, up to 100 days
Overall survival
time frame: From the date of transplant with death from any cause as a censored event, up to 100 days
Transplant-related mortality (TRM) defined as any mortality after transplantation except mortality from relapsed disease
time frame: At day 100

Eligibility Criteria

Male or female participants from 19 years up to 75 years old.

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

Additional Information

Official title RITUXIMAB FOR PREVENTION OF ACUTE GRAFT-VERSUS-HOST DISEASE (GVHD) AFTER UNRELATED DONOR ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (HCT)
Principal investigator Robert Bociek
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.
Trial information was received from ClinicalTrials.gov and was last updated in May 2014.
Information provided to ClinicalTrials.gov by University of Nebraska.