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

NCT00119392 | Completed Phase 2 Results DMC

• 2 other identifiers: 1726.00NCI-2010-01381
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Overall and Progression-free Survival

  Up to 8 years

• Response Rates

  Up to 8 years

• Engraftment and Hematopoietic Toxicity

  At day +100

• Incidence and Severity of Acute Graft-versus-host Disease (GVHD) and Chronic GVHD.

  At day +84

Study Arms (1)

Treatment (90Y ibritumomab tiuxetan, hematopoietic transplant)

EXPERIMENTAL

See Detailed Description

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

Interventions

rituximab BIOLOGICAL

Given IV

Also known as: IDEC-C2B8, IDEC-C2B8 monoclonal antibody, Mabthera, MOAB IDEC-C2B8, Rituxan

Treatment (90Y ibritumomab tiuxetan, hematopoietic transplant)

cyclosporine DRUG

Given orally

Also known as: ciclosporin, cyclosporin, cyclosporin A, CYSP, Sandimmune

Treatment (90Y ibritumomab tiuxetan, hematopoietic transplant)

fludarabine phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, Beneflur, Fludara

Treatment (90Y ibritumomab tiuxetan, hematopoietic transplant)

mycophenolate mofetil DRUG

Given orally

Also known as: Cellcept, MMF

Treatment (90Y ibritumomab tiuxetan, hematopoietic transplant)

yttrium Y 90 ibritumomab tiuxetan RADIATION

Given IV

Also known as: 90Y ibritumomab tiuxetan, IDEC Y2B8, Y90 Zevalin, Y90-labeled ibritumomab tiuxetan

Treatment (90Y ibritumomab tiuxetan, hematopoietic transplant)

peripheral blood stem cell transplantation PROCEDURE

Undergo transplantation

Also known as: PBPC transplantation, PBSC transplantation, peripheral blood progenitor cell transplantation, transplantation, peripheral blood stem cell

Treatment (90Y ibritumomab tiuxetan, hematopoietic transplant)

allogeneic hematopoietic stem cell transplantation PROCEDURE

Undergo transplantation

Treatment (90Y ibritumomab tiuxetan, hematopoietic transplant)

total-body irradiation RADIATION

Undergo TBI

Also known as: TBI

Treatment (90Y ibritumomab tiuxetan, hematopoietic transplant)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

Related Publications (2)

• 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.

  PMID: 30454872 DERIVED

• 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.

  PMID: 21508413 DERIVED

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, B-Cell, Marginal Zone; Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Lymphoma, Large-Cell, Immunoblastic; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Waldenstrom Macroglobulinemia

Interventions

Rituximab; Cyclosporine; fludarabine phosphate; Mycophenolic Acid; ibritumomab tiuxetan; Peripheral Blood Stem Cell Transplantation; Whole-Body Irradiation

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma, B-Cell; Lymphoma; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Radiotherapy; Investigative Techniques

Results Point of Contact

• Title: Ajay Gopal
• Organization: Fred Hutchinson Cancer Research Center

akgopal@fhcrc.org

206-288-2037

Study Officials

• Ajay Gopal

  Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 12, 2005
• First Posted: July 13, 2005
• Study Start: June 1, 2004
• Primary Completion: July 1, 2009
• Study Completion: April 23, 2016
• Last Updated: June 29, 2018
• Results First Posted: May 24, 2017

Record last verified: 2018-06

Locations

US (1)