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

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) 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.

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:	November 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 Gengraf 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 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 CT-P10 IDEC-102 IDEC-C2B8 IDEC-C2B8 Monoclonal Antibody MabThera Monoclonal Antibody IDEC-C2B8 PF-05280586 Rituxan Rituximab Biosimilar BI 695500 Rituximab Biosimilar CT-P10 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

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
Gengraf
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
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
CT-P10
IDEC-102
IDEC-C2B8
IDEC-C2B8 Monoclonal Antibody
MabThera
Monoclonal Antibody IDEC-C2B8
PF-05280586
Rituxan
Rituximab Biosimilar BI 695500
Rituximab Biosimilar CT-P10
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 (Adult, Senior)
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 2398.00 P01CA044991 P30CA015704
Study First Received:	July 26, 2011
Last Updated:	July 8, 2016
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Lymphoma Lymphoma, Non-Hodgkin Lymphoma, B-Cell Lymphoma, Large B-Cell, Diffuse Burkitt Lymphoma Lymphoproliferative Disorders Neoplasms by Histologic Type Neoplasms Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Epstein-Barr Virus Infections Herpesviridae Infections DNA Virus Infections Virus Diseases	Tumor Virus Infections Fludarabine Fludarabine phosphate Rituximab Mycophenolic Acid Antibodies Immunoglobulins Antibodies, Monoclonal Mycophenolate mofetil Cyclosporins Cyclosporine Vidarabine Antineoplastic Agents Immunologic Factors Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 27, 2016