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

NCT ID: NCT01434472

Last Updated: 2021-07-20

Study Results

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-11-16

Study Completion Date

2020-05-06

Brief Summary

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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.

Detailed Description

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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:

Beginning 24-48 hours prior to therapy infusion, patients receive rituximab intravenously (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 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 up to 2 years thereafter.

Conditions

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Treatment (radiolabeled antibody, TBI, allogeneic PBSCT)

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).

Group Type EXPERIMENTAL

Allogeneic Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

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

Cyclosporine

Intervention Type DRUG

Given PO

Fludarabine Phosphate

Intervention Type DRUG

Given IV

Indium In-111 Ibritumomab Tiuxetan

Intervention Type RADIATION

Given IV

Mycophenolate Mofetil

Intervention Type DRUG

Given PO

Pharmacological Study

Intervention Type OTHER

Correlative studies

Rituximab

Intervention Type BIOLOGICAL

Given IV prior to yttrium Y 90 ibritumomab tiuxetan

Total-Body Irradiation

Intervention Type RADIATION

Undergo TBI

Yttrium Y-90 Ibritumomab Tiuxetan

Intervention Type RADIATION

Given IV

Fludarabine

Intervention Type DRUG

Given IV

Interventions

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Allogeneic Hematopoietic Stem Cell Transplantation

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

Intervention Type PROCEDURE

Cyclosporine

Given PO

Intervention Type DRUG

Fludarabine Phosphate

Given IV

Intervention Type DRUG

Indium In-111 Ibritumomab Tiuxetan

Given IV

Intervention Type RADIATION

Mycophenolate Mofetil

Given PO

Intervention Type DRUG

Pharmacological Study

Correlative studies

Intervention Type OTHER

Rituximab

Given IV prior to yttrium Y 90 ibritumomab tiuxetan

Intervention Type BIOLOGICAL

Total-Body Irradiation

Undergo TBI

Intervention Type RADIATION

Yttrium Y-90 Ibritumomab Tiuxetan

Given IV

Intervention Type RADIATION

Fludarabine

Given IV

Intervention Type DRUG

Other Intervention Names

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allogeneic stem cell transplantation HSC HSCT 27-400 Ciclosporin CsA Cyclosporin Cyclosporin A Gengraf Neoral OL 27-400 Sandimmun Sandimmune SangCya 2-F-ara-AMP 9H-Purin-6-amine, 2-fluoro-9-(5-O-phosphono-.beta.-D-arabinofuranosyl)- Beneflur Fludara SH T 586 IDEC In2B8 IDEC-In2B8 In 111 Ibritumomab Tiuxetan In 111 Zevalin indium In 111 ibritumomab tiuxetan Cellcept MMF 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 TOTAL BODY IRRADIATION Whole-Body Irradiation TBI Whole Body Irradiation IDEC-Y2B8 IDEC-Y2B8 monoclonal antibody Y 90 Ibritumomab Tiuxetan Y 90 Zevalin Yttrium Y 90 Ibritumomab Tiuxetan yttrium Y90 ibritumomab tiuxetan 118218 2-Fluoro-9-beta-arabinofuranosyladenine 2-Fluorovidarabine 9-Beta-D-arabinofuranosyl-2-fluoro-9H-purin-6-amine Fluradosa

Eligibility Criteria

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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

* 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)
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Ajay Gopal

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Ajay Gopal

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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NCI-2011-01189

Identifier Type: REGISTRY

Identifier Source: secondary_id

2398.00

Identifier Type: OTHER

Identifier Source: secondary_id

P01CA044991

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA015704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

RG9213033

Identifier Type: OTHER

Identifier Source: secondary_id

2398.00

Identifier Type: -

Identifier Source: org_study_id

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