Rituximab in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer - Full Text View

Sponsor:	University of Nebraska
Collaborator:	National Cancer Institute (NCI)
Information provided by:	University of Nebraska
ClinicalTrials.gov Identifier:	NCT01044745

Purpose

RATIONALE: 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.

PURPOSE: 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

Condition	Intervention	Phase
Leukemia, Myeloid, Accelerated Phase Adult Acute Lymphoblastic Leukemia in Remission Adult Acute Myeloid Leukemia in Remission Adult Nasal Type Extranodal NK/T-cell Lymphoma Blast Phase Contiguous Stage II Adult Burkitt's 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 Mucosa-Associated Lymphoid Tissue Lymphoma Graft Versus Host Disease Monocytoid B-cell Lymphoma Noncontiguous Stage II Adult Burkitt's 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's 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 Adult T-cell Lymphoma/Leukaemia Recurrent Cutaneous T-cell Lymphoma Recurrent Recurrent Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Mantle Cell Lymphoma Recurrent Recurrent Marginal Zone Lymphoma Mycosis Fungoides/Sezary Syndrome Recurrent B-cell Small Lymphocytic Lymphoma Recurrent Chronic Lymphocytic Leukaemia Refractory Chronic Myelogenous Leukemia in Relapse Secondary Myelodysplastic Syndromes Splenic Marginal Zone B-Cell Lymphoma Stage I Adult Burkitt's 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 Adult T-cell Lymphoma/Leukaemia Stage I Chronic Lymphocytic Leukaemia Stage 1 Cutaneous T-cell Lymphoma Stage I Stage I Grade 1 Follicular Lymphoma Stage I Grade 2 Follicular Lymphoma Stage I Grade 3 Follicular Lymphoma Mantle Cell Lymphoma Stage I Stage I Marginal Zone Lymphoma Mycosis Fungoides/Sezary Syndrome Stage I B-cell Small Lymphocytic Lymphoma Stage I Adult T-cell Lymphoma/Leukaemia Stage II Chronic Lymphocytic Leukaemia Stage 2 Cutaneous T-cell Lymphoma Stage II Mycosis Fungoides/Sezary Syndrome Stage II Stage III Adult Burkitt's 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 Adult T-cell Lymphoma/Leukaemia Stage III Chronic Lymphocytic Leukaemia Stage 3 Cutaneous T-cell Lymphoma Stage III Stage III Grade 1 Follicular Lymphoma Stage III Grade 2 Follicular Lymphoma Stage III Grade 3 Follicular Lymphoma Mantle Cell Lymphoma Stage III Stage III Marginal Zone Lymphoma Mycosis Fungoides/Sezary Syndrome Stage III B-cell Small Lymphocytic Lymphoma Stage III Stage IV Adult Burkitt's 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 Adult T-cell Lymphoma/Leukaemia Stage IV Chronic Lymphocytic Leukaemia Stage 4 Cutaneous T-cell Lymphoma Stage IV Stage IV Grade 1 Follicular Lymphoma Stage IV Grade 2 Follicular Lymphoma Stage IV Grade 3 Follicular Lymphoma Mantle Cell Lymphoma Stage IV Stage IV Marginal Zone Lymphoma Mycosis Fungoides/Sezary Syndrome Stage IV B-cell Small Lymphocytic Lymphoma Stage IV Untreated Adult Acute Lymphoblastic Leukemia Untreated Adult Acute Myeloid Leukemia Waldenstrom Macroglobulinemia	Drug: rituximab Drug: mycophenolate mofetil Drug: tacrolimus Drug: anti-thymocyte globulin Procedure: allogeneic hematopoietic stem cell transplantation Other: laboratory biomarker analysis Biological: graft versus host disease prophylaxis/therapy Drug: cyclophosphamide Drug: fludarabine phosphate Drug: busulfan Radiation: total-body irradiation Biological: graft-versus-tumor induction therapy Biological: immunosuppressive therapy	Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	RITUXIMAB FOR PREVENTION OF ACUTE GRAFT-VERSUS-HOST DISEASE (GVHD) AFTER UNRELATED DONOR ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION (HCT)

Resource links provided by NLM:

Genetics Home Reference related topics: aceruloplasminemia familial acute myeloid leukemia with mutated CEBPA hemophilia

MedlinePlus related topics: Acute Lymphocytic Leukemia Acute Myeloid Leukemia Cancer Chronic Lymphocytic Leukemia Chronic Myeloid Leukemia Fungal Infections Leukemia Lymphoma Myelodysplastic Syndromes

Drug Information available for: Cyclophosphamide Busulfan Fludarabine Fludarabine phosphate Tacrolimus Mycophenolate mofetil hydrochloride Mycophenolate mofetil Rituximab Antilymphocyte Serum

U.S. FDA Resources

Further study details as provided by University of Nebraska:

Primary Outcome Measures:

Incidence of grades II-IV acute GVHD [ Time Frame: At day 100 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Event-free survival [ Time Frame: After matched unrelated donor allogeneic HCT ] [ Designated as safety issue: No ]
Overall survival [ Time Frame: After matched unrelated donor allogeneic HCT ] [ Designated as safety issue: No ]
Transplant-related mortality (TRM) [ Time Frame: At day 100 ] [ Designated as safety issue: No ]

Estimated Enrollment:	50
Study Start Date:	December 2009
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.	Drug: rituximab Given IV Other Names: IDEC-C2B8 IDEC-C2B8 monoclonal antibody Mabthera MOAB IDEC-C2B8 Rituxan Drug: mycophenolate mofetil Given IV or PO Other Names: Cellcept MMF Drug: tacrolimus Given IV Other Names: FK 506 Prograf Drug: anti-thymocyte globulin Given IV Other Names: ATG ATGAM lymphocyte immune globulin Thymoglobulin Procedure: allogeneic hematopoietic stem cell transplantation Stem cell transplant Other: laboratory biomarker analysis Correlative studies 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: CPM CTX Cytoxan Endoxan Endoxana Drug: fludarabine phosphate Given IV Other Names: 2-F-ara-AMP Beneflur Fludara Drug: busulfan Given IV Other Names: BSF BU Misulfan Mitosan Myeloleukon Radiation: total-body irradiation Undergo TBI Other Name: TBI 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 Name: immunosuppression

Arms

Assigned Interventions

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.

Drug: rituximab

Given IV

Other Names:

IDEC-C2B8
IDEC-C2B8 monoclonal antibody
Mabthera
MOAB IDEC-C2B8
Rituxan

Drug: mycophenolate mofetil

Given IV or PO

Other Names:

Cellcept
MMF

Drug: tacrolimus

Given IV

Other Names:

FK 506
Prograf

Drug: anti-thymocyte globulin

Given IV

Other Names:

ATG
ATGAM
lymphocyte immune globulin
Thymoglobulin

Procedure: allogeneic hematopoietic stem cell transplantation

Stem cell transplant

Other: laboratory biomarker analysis

Correlative studies

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:

CPM
CTX
Cytoxan
Endoxan
Endoxana

Drug: fludarabine phosphate

Given IV

Other Names:

2-F-ara-AMP
Beneflur
Fludara

Drug: busulfan

Given IV

Other Names:

BSF
BU
Misulfan
Mitosan
Myeloleukon

Radiation: total-body irradiation

Undergo TBI

Other Name: TBI

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 Name: immunosuppression

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 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.

Eligibility

Ages Eligible for Study:	19 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01044745

Contacts

Contact: Mary Mailliard, RN BSN OCN	402-559-5582	mjmailli@unmc.edu
Contact: Marsha Ketcham, RN OCN	402-559-5286	mketcham@unmc.edu

Locations

United States, Nebraska
UNMC Eppley Cancer Center at the University of Nebraska Medical Center	Recruiting
Omaha, Nebraska, United States, 68198-6805
Contact: Robert G. Bociek 402-559-5388 rgbociek@unmc.edu
Principal Investigator: Robert G. Bociek

Sponsors and Collaborators

University of Nebraska

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Robert Bociek

University of Nebraska

More Information

No publications provided

Responsible Party:	Bociek, Robert, UNMC Eppley Cancer Center at the University of Nebraska Medical Center
ClinicalTrials.gov Identifier:	NCT01044745 History of Changes
Other Study ID Numbers:	083-09, NCI-2009-01552, P30CA036727
Study First Received:	January 7, 2010
Last Updated:	March 23, 2011
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:

Blast Crisis
Burkitt Lymphoma
Graft vs Host Disease
Leukemia
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Leukemia, Myeloid
Leukemia, Myeloid, Accelerated Phase
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Leukemia-Lymphoma, Adult T-Cell
Lymphoma
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse

Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Waldenstrom Macroglobulinemia
Mycoses
Mycosis Fungoides
Myelodysplastic Syndromes
Preleukemia
Sezary Syndrome
Lymphoma, B-Cell
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, T-Cell
Lymphoma, T-Cell, Cutaneous
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Mantle-Cell

ClinicalTrials.gov processed this record on May 24, 2012