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 April 2014 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01434472
First received: July 26, 2011
Last updated: April 25, 2014
Last verified: April 2014
  Purpose

This phase II trial studies the side effects and how well high-dose yttrium-90 (Y-90)-ibritumomab tiuxetan (anti-CD20) followed by fludarabine phosphate, low-dose total body irradiation (TBI), and donor peripheral blood stem cell transplant (PBSCT) works in treating patients with relapsed or refractory aggressive B-cell lymphoma. 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
B-cell Adult Acute Lymphoblastic Leukemia
Post-transplant Lymphoproliferative Disorder
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Burkitt Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Adult Diffuse Mixed Cell Lymphoma
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Recurrent Grade 3 Follicular Lymphoma
Recurrent Mantle Cell Lymphoma
Radiation: indium In 111 ibritumomab tiuxetan
Radiation: yttrium Y 90 ibritumomab tiuxetan
Biological: rituximab
Radiation: total-body irradiation
Procedure: allogeneic hematopoietic stem cell transplantation
Drug: fludarabine phosphate
Drug: cyclosporine
Drug: mycophenolate mofetil
Other: pharmacological study
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:
  • 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.

  • Overall survival [ Time Frame: Up to 2 years ] [ Designated as safety issue: No ]
  • Response rates [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
  • Engraftment and hematopoietic toxicity [ Time Frame: Up to day 100 ] [ Designated as safety issue: Yes ]
    Engraftment assessed by need for blood transfusion support. Toxicity graded in severity according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 4.


Estimated Enrollment: 24
Study Start Date: November 2011
Estimated Primary Completion Date: April 2014 (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).
Radiation: indium In 111 ibritumomab tiuxetan
Given IV
Other Name: IDEC-In2B8
Radiation: yttrium Y 90 ibritumomab tiuxetan
Given IV
Other Names:
  • 90Y ibritumomab tiuxetan
  • IDEC Y2B8
  • Y90 Zevalin
  • Y90-labeled ibritumomab tiuxetan
Biological: rituximab
Given IV prior to yttrium Y 90 ibritumomab tiuxetan
Other Names:
  • IDEC-C2B8
  • IDEC-C2B8 monoclonal antibody
  • Mabthera
  • MOAB IDEC-C2B8
  • Rituxan
Radiation: total-body irradiation
Undergo TBI
Other Name: TBI
Procedure: allogeneic hematopoietic stem cell transplantation
Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter)
Drug: fludarabine phosphate
Given IV
Other Names:
  • 2-F-ara-AMP
  • Beneflur
  • Fludara
Drug: cyclosporine
Given PO
Other Names:
  • ciclosporin
  • cyclosporin
  • cyclosporin A
  • CYSP
  • Sandimmune
Drug: mycophenolate mofetil
Given PO
Other Names:
  • Cellcept
  • MMF
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

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 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 cluster of differentiation (CD)20 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
  • 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 Hutchinson Cancer Research Center/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Ajay K. Gopal    206-288-2037      
Principal Investigator: Ajay K. Gopal         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
Investigators
Principal Investigator: Ajay Gopal Fred Hutchinson Cancer Research Center/University of Washington Cancer Consortium
  More Information

No publications provided

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01434472     History of Changes
Other Study ID Numbers: 2398.00, NCI-2011-01189, 2398.00, P01CA044991, P30CA015704
Study First Received: July 26, 2011
Last Updated: April 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Burkitt Lymphoma
Leukemia
Leukemia, Lymphoid
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Follicular
Lymphomatoid Granulomatosis
Lymphoproliferative Disorders
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Mantle-Cell
Epstein-Barr Virus Infections
Herpesviridae Infections
DNA Virus Infections
Virus Diseases
Tumor Virus Infections
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Experimental
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Precancerous Conditions
Lymphoma, T-Cell
Antibodies
Antibodies, Monoclonal
Cyclosporins

ClinicalTrials.gov processed this record on August 20, 2014