Brief Title
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
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 Phase
Phase 2
Study Type
Interventional
Primary Outcome
Treatment Related Mortality (TRM)
Secondary Outcome
Overall and Progression-free Survival
Condition
B-cell Chronic Lymphocytic Leukemia
Intervention
rituximab
Study Arms / Comparison Groups
Treatment (90Y ibritumomab tiuxetan, hematopoietic transplant)
Description: See Detailed Description
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Estimated Enrollment
42
Start Date
June 2004
Completion Date
April 23, 2016
Primary Completion Date
July 2009
Eligibility 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Ajay Gopal, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00119392
Organization ID
1726.00
Secondary IDs
NCI-2010-01381
Responsible Party
Principal Investigator
Study Sponsor
Fred Hutchinson Cancer Center
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Ajay Gopal, Principal Investigator, Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
Verification Date
June 2018