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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
R. Gregory Bociek, MD, University of Nebraska
ClinicalTrials.gov Identifier:
NCT01044745
First received: January 7, 2010
Last updated: May 28, 2014
Last verified: May 2014
  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. 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


Condition Intervention Phase
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
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:


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 ]
    Determined with death as a competing risk. Defined and staged using the 1994 consensus conference modifications of the Glucksberg criteria.


Secondary Outcome Measures:
  • Event-free survival [ Time Frame: From the date of transplant with relapse/progression or death as censored events, up to 100 days ] [ Designated as safety issue: No ]
    Estimated using Kaplan-Meier estimator.

  • Overall survival [ Time Frame: From the date of transplant with death from any cause as a censored event, up to 100 days ] [ Designated as safety issue: No ]
    Estimated using Kaplan-Meier estimator.

  • Transplant-related mortality (TRM) defined as any mortality after transplantation except mortality from relapsed disease [ Time Frame: At day 100 ] [ Designated as safety issue: No ]
    Reported as a simple percentage.


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

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.

  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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Nebraska
University of Nebraska Medical Center
Omaha, Nebraska, United States, 68198-7830
Sponsors and Collaborators
University of Nebraska
Investigators
Principal Investigator: Robert Bociek University of Nebraska
  More Information

No publications provided

Responsible Party: R. Gregory Bociek, MD, Principal Investigator, University of Nebraska
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: May 28, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Follicular
Burkitt Lymphoma
Lymphoma, Large-Cell, Immunoblastic
Leukemia, T-Cell
Leukemia-Lymphoma, Adult T-Cell
Leukemia, Myeloid
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Myeloid, Acute
Lymphomatoid Granulomatosis
Waldenstrom Macroglobulinemia
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Mantle-Cell
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Lymphoma, Large B-Cell, Diffuse
Mycoses
Graft vs Host Disease
Mycosis Fungoides
Leukemia
Lymphoma, T-Cell
Sezary Syndrome
Lymphoma, T-Cell, Cutaneous
Myelodysplastic Syndromes
Preleukemia
Lymphoma, Extranodal NK-T-Cell
Blast Crisis
Leukemia, Myeloid, Accelerated Phase

ClinicalTrials.gov processed this record on September 16, 2014