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

NCT ID: NCT00119392

Last Updated: 2018-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-06-30
• Study Completion Date: 2016-04-23

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.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (90Y ibritumomab tiuxetan, hematopoietic transplant)

See Detailed Description

Group Type: EXPERIMENTAL

rituximab

Intervention Type: BIOLOGICAL

Given IV

cyclosporine

Intervention Type: DRUG

Given orally

fludarabine phosphate

Intervention Type: DRUG

Given IV

mycophenolate mofetil

Intervention Type: DRUG

Given orally

yttrium Y 90 ibritumomab tiuxetan

Intervention Type: RADIATION

Given IV

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

Undergo transplantation

allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

Undergo transplantation

total-body irradiation

Intervention Type: RADIATION

Undergo TBI

Interventions

rituximab

Given IV

Intervention Type: BIOLOGICAL

cyclosporine

Given orally

Intervention Type: DRUG

fludarabine phosphate

Given IV

Intervention Type: DRUG

mycophenolate mofetil

Given orally

Intervention Type: DRUG

yttrium Y 90 ibritumomab tiuxetan

Given IV

Intervention Type: RADIATION

peripheral blood stem cell transplantation

Undergo transplantation

Intervention Type: PROCEDURE

allogeneic hematopoietic stem cell transplantation

Undergo transplantation

Intervention Type: PROCEDURE

total-body irradiation

Undergo TBI

Intervention Type: RADIATION

Other Intervention Names

IDEC-C2B8; IDEC-C2B8 monoclonal antibody; Mabthera; MOAB IDEC-C2B8; Rituxan; ciclosporin; cyclosporin; cyclosporin A; CYSP; Sandimmune; 2-F-ara-AMP; Beneflur; Fludara; Cellcept; MMF; 90Y ibritumomab tiuxetan; IDEC Y2B8; Y90 Zevalin; Y90-labeled ibritumomab tiuxetan; PBPC transplantation; PBSC transplantation; peripheral blood progenitor cell transplantation; transplantation, peripheral blood stem cell; TBI

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Ajay Gopal

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ajay Gopal

Role: PRINCIPAL_INVESTIGATOR

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Locations

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, United States

Countries

United States

References

Puronen CE, Cassaday RD, Stevenson PA, Sandmaier BM, Flowers ME, Green DJ, Maloney DG, Storb RF, Press OW, Gopal AK. Long-Term Follow-Up of 90Y-Ibritumomab Tiuxetan, Fludarabine, and Total Body Irradiation-Based Nonmyeloablative Allogeneic Transplant Conditioning for Persistent High-Risk B Cell Lymphoma. Biol Blood Marrow Transplant. 2018 Nov;24(11):2211-2215. doi: 10.1016/j.bbmt.2018.06.033. Epub 2018 Jul 3.

Reference Type: DERIVED

PMID: 30454872 (View on PubMed)

Gopal AK, Guthrie KA, Rajendran J, Pagel JM, Oliveira G, Maloney DG, Matesan MC, Storb RF, Press OW. (9)(0)Y-Ibritumomab tiuxetan, fludarabine, and TBI-based nonmyeloablative allogeneic transplantation conditioning for patients with persistent high-risk B-cell lymphoma. Blood. 2011 Jul 28;118(4):1132-9. doi: 10.1182/blood-2010-12-324392. Epub 2011 Apr 20.

Reference Type: DERIVED

PMID: 21508413 (View on PubMed)

Other Identifiers

NCI-2010-01381

Identifier Type: REGISTRY

Identifier Source: secondary_id

1726.00

Identifier Type: -

Identifier Source: org_study_id