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

Recurrent Mantle Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00119392
• Other study ID #: 1726.00
• Secondary ID: NCI-2010-01381
• Status: Completed
• Phase: Phase 2
• Start date: June 2004
• Est. completion date: April 23, 2016

Study information

• Verified date: June 2018
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: April 23, 2016
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• B-cell Chronic Lymphocytic Leukemia
• Burkitt Lymphoma
• Leukemia, Lymphocytic, Chronic, B-Cell
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, B-Cell, Marginal Zone
• Lymphoma, Extranodal NK-T-Cell
• Lymphoma, Follicular
• Lymphoma, Large B-Cell, Diffuse
• Lymphoma, Large-Cell, Immunoblastic
• Lymphoma, Mantle-Cell
• Lymphoma, Non-Hodgkin
• Lymphomatoid Granulomatosis
• Nodal Marginal Zone B-cell Lymphoma
• Plasmablastic Lymphoma
• Precursor Cell Lymphoblastic Leukemia-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
• Waldenstrom Macroglobulinemia
• Waldenström Macroglobulinemia

Intervention

Biological:
• rituximab
Given IV

Drug:
• cyclosporine
Given orally
• fludarabine phosphate
Given IV
• mycophenolate mofetil
Given orally

Radiation:
• yttrium Y 90 ibritumomab tiuxetan
Given IV

Procedure:
• peripheral blood stem cell transplantation
Undergo transplantation
• allogeneic hematopoietic stem cell transplantation
Undergo transplantation

Radiation:
• total-body irradiation
Undergo TBI

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treatment Related Mortality (TRM)	Cumulative incidence rate of treatment related mortality with relapse as a competing risk, assessed at 30 months.	At day +100
Secondary	Overall and Progression-free Survival	Kaplan-Meier estimates for overall survival (OS) and progression free survival (PFS) assessed at two years.	Up to 8 years
Secondary	Response Rates		Up to 8 years
Secondary	Engraftment and Hematopoietic Toxicity	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.	At day +100
Secondary	Incidence and Severity of Acute Graft-versus-host Disease (GVHD) and Chronic GVHD.		At day +84