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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

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ClinicalTrials.gov Identifier: NCT00119392
Recruitment Status : Completed
First Posted : July 13, 2005
Results First Posted : May 24, 2017
Last Update Posted : June 29, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Ajay Gopal, Fred Hutchinson Cancer Research Center

Tracking Information
First Submitted Date  ICMJE July 12, 2005
First Posted Date  ICMJE July 13, 2005
Results First Submitted Date  ICMJE April 17, 2017
Results First Posted Date  ICMJE May 24, 2017
Last Update Posted Date June 29, 2018
Study Start Date  ICMJE June 2004
Actual Primary Completion Date July 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 17, 2017)
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.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 17, 2017)
  • 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 ]
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Yttrium Y 90 Ibritumomab Tiuxetan, Fludarabine, Radiation Therapy, and Donor Stem Cell Transplant in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Official Title  ICMJE 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
Brief Summary 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
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • 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
Intervention  ICMJE
  • 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
Study Arms  ICMJE Experimental: Treatment (90Y ibritumomab tiuxetan, hematopoietic transplant)
See Detailed Description
Interventions:
  • 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
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: April 17, 2017)
42
Original Enrollment  ICMJE Not Provided
Actual Study Completion Date  ICMJE April 23, 2016
Actual Primary Completion Date July 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00119392
Other Study ID Numbers  ICMJE 1726.00
NCI-2010-01381 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Ajay Gopal, Fred Hutchinson Cancer Research Center
Study Sponsor  ICMJE Fred Hutchinson Cancer Research Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Ajay Gopal Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
PRS Account Fred Hutchinson Cancer Research Center
Verification Date June 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP