High-Dose Y-90-Ibritumomab Tiuxetan Added to Reduced-Intensity Allogeneic Stem Cell Transplant Regimen for Relapsed or Refractory Aggressive B-Cell Lymphoma

NCT01434472 | Terminated Phase 2 Results

• 5 other identifiers: 2398.00NCI-2011-01189P01CA044991P30CA015704RG9213033
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This phase II trial studies the side effects and how well high-dose yttrium-90 (Y-90)-ibritumomab tiuxetan (anti-cluster of differentiation \[CD\]20) followed by fludarabine phosphate, low-dose total body irradiation (TBI), and donor peripheral blood stem cell transplant (PBSCT) work in treating patients with aggressive B-cell lymphoma that has returned after a period of improvement (relapsed) or has not responded to previous treatment (refractory). Radiolabeled monoclonal antibodies, such as Y-90-ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them with less effect on normal cells. Giving chemotherapy, such as fludarabine phosphate, and TBI before a donor PBSCT helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. However, high-dose radiolabeled antibodies also destroy healthy blood cells in the patient's body. When healthy stem cells from a donor are infused into the patient (stem cell transplant), they may help the patient's body replace these blood cells. Giving high-dose Y-90-ibritumomab tiuxetan followed by fludarabine phosphate, TBI, and donor PBSCT may be an effective treatment for patients with B-cell lymphoma.

Conditions

Post-Transplant Lymphoproliferative Disorder; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Burkitt Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Burkitt Lymphoma; Refractory Diffuse Large B-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival

  Based on a one-sample chi-square test with one-sided significance level of five percent. This study will be deemed successful if the 1 year progression-free survival of this highest-risk group of patients is 54% or greater.

  1 year

Secondary Outcomes (6)

• Absolute Neutrophil Count (ANC) Engraftment

  Up to day 100

• Overall Survival

  Up to 2 years post transplant

• Response Rates

  Day 100

• Treatment-related Mortality

  Day 100

• Platelet Engraftment

  Up to day 100

Study Arms (1)

Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)

EXPERIMENTAL

Beginning 24-48 hours prior to therapy infusion, patients receive rituximab IV over 4-6 hours and then receive a therapy-dose of high-dose yttrium Y 90 ibritumomab tiuxetan IV over 30 minutes on day -14 prior to transplant. Patients also receive fludarabine phosphate IV on days -4 to -2 and undergo TBI followed by allogeneic PBSCT on day 0. Patients also receive cyclosporine PO BID on days -3 to 56 with taper to day 180 (related donor) or -3 to 100 with taper over 11 weeks (unrelated donor) and mycophenolate mofetil PO BID on days 0-27 (related donor) or PO TID on days 0-40 with taper to day 96 (unrelated donor).

Procedure: Allogeneic Hematopoietic Stem Cell Transplantation; Drug: Cyclosporine; Drug: Fludarabine Phosphate; Radiation: Indium In-111 Ibritumomab Tiuxetan; Drug: Mycophenolate Mofetil; Other: Pharmacological Study; Biological: Rituximab; Radiation: Total-Body Irradiation; Radiation: Yttrium Y-90 Ibritumomab Tiuxetan; Drug: Fludarabine

Interventions

Allogeneic Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter)

Also known as: allogeneic stem cell transplantation, HSC, HSCT

Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)

Cyclosporine DRUG

Given PO

Also known as: 27-400, Ciclosporin, CsA, Cyclosporin, Cyclosporin A, Gengraf, Neoral, OL 27-400, Sandimmun, Sandimmune, SangCya

Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)

Fludarabine Phosphate DRUG

Given IV

Also known as: 2-F-ara-AMP, 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-, Beneflur, Fludara, SH T 586

Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)

Indium In-111 Ibritumomab Tiuxetan RADIATION

Given IV

Also known as: IDEC In2B8, IDEC-In2B8, In 111 Ibritumomab Tiuxetan, In 111 Zevalin, indium In 111 ibritumomab tiuxetan

Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)

Mycophenolate Mofetil DRUG

Given PO

Also known as: Cellcept, MMF

Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)

Pharmacological Study OTHER

Correlative studies

Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)

Rituximab BIOLOGICAL

Given IV prior to yttrium Y 90 ibritumomab tiuxetan

Also known as: ABP 798, BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, CT-P10, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar ABP 798, Rituximab Biosimilar BI 695500, Rituximab Biosimilar CT-P10, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, Rituximab Biosimilar SAIT101, RTXM83

Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)

Total-Body Irradiation RADIATION

Undergo TBI

Also known as: TOTAL BODY IRRADIATION, Whole-Body Irradiation, TBI, Whole Body Irradiation

Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)

Yttrium Y-90 Ibritumomab Tiuxetan RADIATION

Given IV

Also known as: IDEC-Y2B8, IDEC-Y2B8 monoclonal antibody, Y 90 Ibritumomab Tiuxetan, Y 90 Zevalin, Yttrium Y 90 Ibritumomab Tiuxetan, yttrium Y90 ibritumomab tiuxetan

Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)

Fludarabine DRUG

Given IV

Also known as: 118218, 2-Fluoro-9-beta-arabinofuranosyladenine, 2-Fluorovidarabine, 9-Beta-D-arabinofuranosyl-2-fluoro-9H-purin-6-amine, Fluradosa

Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)

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 aggressive B-cell lymphoma (diffuse large B-cell lymphoma \[DLBCL\], Burkitt lymphoma \[BL\], etc.) expressing the CD20 antigen and have failed at least one prior standard systemic therapy
• Patients must have relapsed after high-dose therapy and autologous transplantation or be ineligible for high-dose therapy and autologous transplantation; patients that have failed autologous transplantation are those with persistent disease \> 30 days after transplant; those ineligible for autologous transplant include those with chemoresistant disease (i.e., patients who have not achieved a partial response or better with their most recent chemotherapy regimen), are expected to have a poor outcome from autologous transplant (e.g., DLBCL relapsing within one year of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone \[R-CHOP\]-like chemotherapy, double hit lymphoma, v-myc myelocytomatosis viral oncogene homolog (avian) positive \[MYC+\] lymphoma, persistent positron emission tomography \[PET\] positivity after chemotherapy), are unable to collect sufficient or tumor-free autologous stem cells per Seattle Cancer Care Alliance (SCCA) standard practice, are unable to tolerate the high-dose autologous conditioning regimens, or who refuse a high-dose autologous transplant regimen
• Creatinine (Cr) \< 2.0
• Bilirubin \< 1.5 mg/dL with the exception of patients thought to have Gilbert's syndrome, who may have a total bilirubin above 1.5 mg/dL
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \< 3 x upper limit of normal (ULN)
• Patients must have an expected survival without treatment of \> 60 days and must be free of major infection including human immunodeficiency virus (HIV)
• Patients must have an HLA-identical related or HLA-matched unrelated donor

You may not qualify if:

• Receipt of systemic anti-lymphoma therapy withinthe following intervals prior to the therapeutic 90Y-ibritumomab tiuxetan dose:
• \< 30 days for intravenously-administered cytotoxic chemotherapy and/or monoclonal antibodies
• \< 5 half-lives for all other anti-cancer agents (e.g., targeted therapies, corticosteroids, immunomodulatory agents, etc.)
• Inability to understand or give an informed consent
• Active 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
• High-dose chemotherapy or external beam radiation therapy to lung, liver, or kidneys \> 20 Gy within the previous 100 days prior to therapeutic 90Y-ibritumomab tiuxetan dose
• Medical condition that would contraindicate allogeneic transplantation as per standard practice guidelines (e.g., impaired cardiopulmonary function, hepatitis, etc)

Sponsors & Collaborators

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

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, B-Cell; Burkitt Lymphoma

Interventions

Cyclosporine; Cyclosporins; fludarabine phosphate; Indium; Mycophenolic Acid; Rituximab; CT-P10; Whole-Body Irradiation; ibritumomab tiuxetan; fludarabine

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections

Intervention Hierarchy (Ancestors)

Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Metals, Heavy; Elements; Inorganic Chemicals; Metals; Caproates; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Fatty Acids; Lipids; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Radiotherapy; Therapeutics; Investigative Techniques

Results Point of Contact

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

agopal@uw.edu

206-606-2037

Study Officials

• Ajay Gopal

  Fred Hutch/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: Professor

Study Record Dates

• First Submitted: July 26, 2011
• First Posted: September 15, 2011
• Study Start: November 16, 2011
• Primary Completion: May 6, 2020
• Study Completion: May 6, 2020
• Last Updated: July 20, 2021
• Results First Posted: May 25, 2021

Record last verified: 2021-07

Locations

US (1)