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Yttrium Y 90 Ibritumomab Tiuxetan, Fludarabine, Radiation Therapy, and Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00119392
First Posted: July 13, 2005
Last Update Posted: May 24, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Ajay Gopal, Fred Hutchinson Cancer Research Center
  Purpose
Monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can block find cancer cells and either kill them or carry cancer-killing substances to them without harming normal cells. Giving monoclonal antibodies, low doses of chemotherapy, such as fludarabine phosphate, and low dose total-body radiation therapy before a donor peripheral stem cell transplant helps stop the growth of cancer cells and also stops 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 cyclosporine or mycophenolate mofetil after the transplant may stop this from happening

Condition Intervention Phase
B-cell Chronic Lymphocytic Leukemia Nodal Marginal Zone B-cell Lymphoma 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 Grade 1 Follicular Lymphoma Recurrent Grade 2 Follicular Lymphoma Recurrent Grade 3 Follicular Lymphoma Recurrent Mantle Cell Lymphoma Recurrent Marginal Zone Lymphoma Recurrent Small Lymphocytic Lymphoma Splenic Marginal Zone Lymphoma Waldenström Macroglobulinemia Biological: rituximab Drug: cyclosporine Drug: fludarabine phosphate Drug: mycophenolate mofetil Radiation: yttrium Y 90 ibritumomab tiuxetan Procedure: peripheral blood stem cell transplantation Procedure: allogeneic hematopoietic stem cell transplantation Radiation: total-body irradiation Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Trial Evaluating the Safety and Efficacy of Non-myeloablative 90Y-Ibritumomab Tiuxetan (Anti-CD20) Antibody With Fludarabine, Low-Dose Total Body Irradiation (TBI) and HLA Matched Allogeneic Transplantation for Relapsed B-cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Ajay Gopal, Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Treatment Related Mortality (TRM) [ Time Frame: At day +100 ]
    Cumulative incidence rate of treatment related mortality with relapse as a competing risk, assessed at 30 months.


Secondary Outcome Measures:
  • Overall and Progression-free Survival [ Time Frame: Up to 8 years ]
    Kaplan-Meier estimates for overall survival (OS) and progression free survival (PFS) assessed at two years.

  • Response Rates [ Time Frame: Up to 8 years ]
  • Engraftment and Hematopoietic Toxicity [ Time Frame: At day +100 ]
    Median number of days after transplantation to a neutrophil count less than 500 neutrophils per microliter and a platelet count less than 50,000 platelets per microliter.

  • Incidence and Severity of Acute Graft-versus-host Disease (GVHD) and Chronic GVHD. [ Time Frame: At day +84 ]

Enrollment: 42
Study Start Date: June 2004
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (90Y ibritumomab tiuxetan, hematopoietic transplant)
See Detailed Description
Biological: rituximab
Given IV
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Drug: cyclosporine
Given orally
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Drug: mycophenolate mofetil
Given orally
Other Names:
  • Cellcept
  • MMF
Radiation: yttrium Y 90 ibritumomab tiuxetan
Given IV
Other Names:
  • 90Y ibritumomab tiuxetan
  • IDEC Y2B8
  • Y90 Zevalin
  • Y90-labeled ibritumomab tiuxetan
Procedure: peripheral blood stem cell transplantation
Undergo transplantation
Other Names:
  • PBPC transplantation
  • PBSC transplantation
  • peripheral blood progenitor cell transplantation
  • transplantation, peripheral blood stem cell
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo transplantation
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the feasibility, safety, and potential efficacy of treating patients with B-Cell non-Hodgkin lymphoma (NHL) with 90Y-ibritumomab tiuxetan, combined with HLA-matched related or unrelated donor hematopoietic cell transplantation.

OUTLINE: Patients receive rituximab intravenously (IV) followed by, no more than 4 hours later, indium In 111 ibritumomab tiuxetan (for imaging) IV over 10 minutes on day -21. Patients undergo gamma camera imaging on day -19. Patients receive rituximab IV followed by, no more than 4 hours later, yttrium Y 90 ibritumomab tiuxetan IV over 10 minutes on day -14. Patients also receive fludarabine phosphate IV over 30-60 minutes on days -7 to -5 and undergo low-dose total-body irradiation (TBI) on day 0. After TBI, patients undergo allogeneic peripheral blood stem cell transplantation (PBSCT) on day 0. Patients who undergo PBSCT from a related donor receive oral cyclosporine twice daily on days -3 to 56 followed by a taper to day 180 in the absence of graft-versus-host disease (GVHD). These patients also receive oral mycophenolate mofetil twice daily on days 0 to 27. Patients who undergo PBSCT from an unrelated donor receive oral cyclosporine twice daily on days -3 to 100 followed by a taper over 11 weeks in the absence of GVHD. These patients also receive oral mycophenolate mofetil three times daily on days 0 to 40 followed by a taper to day 96.

After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months, and then annually thereafter.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have a histologically confirmed diagnosis of a lymphoid malignancy expressing the cluster of differentiation (CD)20 antigen and have failed at least one prior standard systemic therapy
  • Patients must have evidence of persistent lymphoma by physical examination, radiographic studies, bone marrow evaluation, flow cytometry, or polymerase chain reaction (PCR)
  • Creatinine < 2.0
  • Bilirubin < 1.5 mg/dL
  • Patients must have an expected survival of > 60 days and must be free of major infection including human immunodeficiency virus (HIV)
  • Patients must have an HLA-identical related or unrelated donor
  • DONOR: Donor eligibility includes both HLA-matched relatives or HLA matched, unrelated volunteer donors; related donors should be matched by molecular methods at the intermediate resolution level at HLA-A, B, C, and DRB1 according to FHCRC Standard Practice Guidelines and to the allele level at DQB1; unrelated donors should be identified using matching criteria that follows the FHCRC Standard Practice Guidelines limiting the study to eligible donors that are allele matched for HLA-A, B, C, DRB1, and DQB1 (Grade1), and accepting up to one allele mismatch as per Standard Practice Grade 2.1 for HLA-A, B, or C
  • Donor must consent to granulocyte colony-stimulating factor (G-CSF) (filgrastim) administration and leukapheresis
  • Donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian)

Exclusion Criteria:

  • Systemic anti-lymphoma therapy given in the previous 30 days
  • Patients who have experienced progressive disease within 3 months of prior Bexxar or Zevalin
  • Inability to understand or give an informed consent
  • Central nervous system lymphoma
  • Pregnancy
  • Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
  • Southwest Oncology Group (SWOG)/Eastern Cooperative Oncology Group (ECOG) performance score > 2
  • Eligible for radioimmunotherapy-based autologous transplant trial
  • Medical condition that would contraindicate allogeneic transplantation
  • Evidence of Human Anti-Mouse Antibody (HAMA) for patients with prior exposure to therapeutic murine antibodies
  • Eligible for other therapeutic options that will be more likely to have a better long-term disease-free survival with lower potential toxicity (e.g., non-transplant therapy, autologous transplants, etc.) than this study
  • Other grave medical conditions considered to represent contraindications to bone marrow transplant (BMT) (e.g. unstable angina, pulmonary dysfunction [diffusing capacity of the lung for carbon monoxide (DLCO) < 30%, total lung capacity (TLC) < 30%, continuous supplemental oxygen], acquired immune deficiency syndrome [AIDS], etc.)
  • DONOR: Identical twin
  • DONOR: Age less than 12 years
  • DONOR: Pregnancy
  • DONOR: Infection with HIV
  • DONOR: Inability to achieve adequate venous access
  • DONOR: Known allergy to G-CSF
  • DONOR: Current serious systemic illness or infection
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00119392


Locations
United States, Washington
Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Ajay Gopal Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ajay Gopal, Principal Investigator, Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT00119392     History of Changes
Other Study ID Numbers: 1726.00
NCI-2010-01381 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Submitted: July 12, 2005
First Posted: July 13, 2005
Results First Submitted: April 17, 2017
Results First Posted: May 24, 2017
Last Update Posted: May 24, 2017
Last Verified: April 2017

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, B-Cell, Marginal Zone
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma, Large B-Cell, Diffuse
Burkitt Lymphoma
Lymphoma, Large-Cell, Immunoblastic
Plasmablastic Lymphoma
Waldenstrom Macroglobulinemia
Lymphomatoid Granulomatosis
Lymphoma, Extranodal NK-T-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia
Leukemia, B-Cell
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms, Plasma Cell