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

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2016 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01434472
First received: July 26, 2011
Last updated: March 14, 2016
Last verified: March 2016
  Purpose
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) works 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.

Condition Intervention Phase
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
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
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Trial of High-Dose 90Y-Ibritumomab Tiuxetan (Anti-CD20) Followed by Fludarabine and Low-Dose Total Body Irradiation and HLA-Matched Allogeneic Hematopoietic Transplantation for Patients With Relapsed or Refractory Aggressive B-Cell Lymphoma

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • Progression-free survival (PFS) [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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 PFS of this highest-risk group of patients is 54% or greater.


Secondary Outcome Measures:
  • Engraftment and hematopoietic toxicity [ Time Frame: Up to day 100 ] [ Designated as safety issue: Yes ]
    Toxicity graded in severity according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.

  • Overall survival [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]
  • Response rates [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
  • Treatment-related mortality [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
    Defined as death in the absence of progressive lymphoma that can be possibly, probably, or definitely attributed to the radioimmunotherapy.


Estimated Enrollment: 24
Study Start Date: November 2011
Estimated Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)
Patients receive a dosimetry test dose of indium In 111 ibritumomab tiuxetan IV over 10 minutes within four weeks prior to transplant and then receive a therapy-dose of high-dose yttrium Y 90 ibritumomab tiuxetan IV over 30 minutes on day -14 prior to transplant. Both ibritumomab tiuxetan infusions may be preceded by rituximab IV, depending on results of blood tests to determine rituximab concentration. Patients 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
Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter)
Other Names:
  • allogeneic stem cell transplantation
  • HSC
  • HSCT
Drug: Cyclosporine
Given PO
Other Names:
  • 27-400
  • Ciclosporin
  • CsA
  • Cyclosporin
  • Cyclosporin A
  • Neoral
  • OL 27-400
  • Sandimmun
  • Sandimmune
  • SangCya
Drug: Fludarabine Phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)-
  • Beneflur
  • Fludara
  • Oforta
  • SH T 586
Radiation: Indium In-111 Ibritumomab Tiuxetan
Given IV
Other Names:
  • IDEC In2B8
  • IDEC-In2B8
  • In 111 Ibritumomab Tiuxetan
  • In 111 Zevalin
  • indium In 111 ibritumomab tiuxetan
Drug: Mycophenolate Mofetil
Given PO
Other Names:
  • Cellcept
  • MMF
Other: Pharmacological Study
Correlative studies
Biological: Rituximab
Given IV prior to yttrium Y 90 ibritumomab tiuxetan
Other Names:
  • BI 695500
  • C2B8 Monoclonal Antibody
  • Chimeric Anti-CD20 Antibody
  • IDEC-102
  • IDEC-C2B8
  • IDEC-C2B8 Monoclonal Antibody
  • MabThera
  • Monoclonal Antibody IDEC-C2B8
  • PF-05280586
  • Rituxan
  • Rituximab Biosimilar BI 695500
  • Rituximab Biosimilar PF-05280586
  • Rituximab Biosimilar RTXM83
  • RTXM83
Radiation: Total-Body Irradiation
Undergo TBI
Other Names:
  • TOTAL BODY IRRADIATION
  • Whole-Body Irradiation
Radiation: Yttrium Y-90 Ibritumomab Tiuxetan
Given IV
Other Names:
  • IDEC-Y2B8
  • IDEC-Y2B8 monoclonal antibody
  • Y 90 Ibritumomab Tiuxetan
  • Y 90 Zevalin
  • Yttrium Y 90 Ibritumomab Tiuxetan
  • yttrium Y90 ibritumomab tiuxetan

Detailed Description:

PRIMARY OBJECTIVES:

I. To assess the safety and efficacy of 1.5 mCi/kg (max 120 mCi) 90Y-Ibritumomab tiuxetan (yttrium Y 90 ibritumomab tiuxetan) (anti-CD20) combined with fludarabine (fludarabine phosphate) (30 mg/m^2 x 3) and 2 gray (Gy) total body irradiation followed by human leukocyte antigens (HLA) matched allogeneic hematopoietic transplantation for patients with relapsed or refractory aggressive B-cell lymphoma.

OUTLINE:

Patients receive a dosimetry test dose of indium In 111 ibritumomab tiuxetan intravenously (IV) over 10 minutes within four weeks prior to transplant and then receive a therapy-dose of high-dose yttrium Y 90 ibritumomab tiuxetan IV over 30 minutes on day -14 prior to transplant. Both ibritumomab tiuxetan infusions may be preceded by rituximab IV, depending on results of blood tests to determine rituximab concentration. Patients receive fludarabine phosphate IV on days -4 to -2 and undergo TBI followed by allogeneic PBSCT on day 0. Patients also receive cyclosporine orally (PO) twice daily (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 thrice daily (TID) on days 0-40 with taper to day 96 (unrelated donor).

After completion of study treatment and assessments through ~day 100 following transplant, patients are followed up at 1, 3, 6, and 12 months and then annually thereafter.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Systemic anti-lymphoma therapy given within 30 days prior to therapeutic 90Y-ibritumomab tiuxetan dose
  • 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)
  • Altered biodistribution (determined following trace-labeled 111In-ibritumomab tiuxetan dose)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01434472

Locations
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Ajay K. Gopal    206-288-2037    agopal@u.washington.edu   
Principal Investigator: Ajay K. Gopal         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Ajay Gopal Fred Hutch/University of Washington Cancer Consortium
  More Information

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01434472     History of Changes
Other Study ID Numbers: 2398.00  NCI-2011-01189  2398  2398.00  P01CA044991  P30CA015704 
Study First Received: July 26, 2011
Last Updated: March 14, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Burkitt Lymphoma
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
DNA Virus Infections
Epstein-Barr Virus Infections
Herpesviridae Infections
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Neoplasms
Neoplasms by Histologic Type
Neoplasms, Experimental
Tumor Virus Infections
Virus Diseases
Antibodies
Antibodies, Monoclonal
Cyclosporine
Cyclosporins
Fludarabine
Fludarabine phosphate
Immunoglobulins
Mycophenolate mofetil
Mycophenolic Acid
Rituximab
Vidarabine
Anti-Infective Agents
Antibiotics, Antineoplastic

ClinicalTrials.gov processed this record on May 05, 2016