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-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:

MedlinePlus related topics: Lymphoma

Drug Information available for: Yttrium Indium Fludarabine Mycophenolic acid Mycophenolate sodium Cyclosporine Fludarabine phosphate Cyclosporin Mycophenolate mofetil hydrochloride Mycophenolate mofetil Rituximab Ibritumomab tiuxetan

Genetic and Rare Diseases Information Center resources: Acute Lymphoblastic Leukemia Acute Monoblastic Leukemia Acute Myeloblastic Leukemia Type 5 B-cell Lymphomas Burkitt Lymphoma Follicular Lymphoma Lymphoblastic Lymphoma Lymphoma, Large-cell Lymphoma, Large-cell, Immunoblastic Lymphomatoid Granulomatosis Lymphosarcoma Mantle Cell Lymphoma Plasmablastic Lymphoma Small Non-cleaved Cell Lymphoma

U.S. FDA Resources

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:	November 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

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

National Cancer Institute (NCI)

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:	October 20, 2014
Health Authority:	United States: Food and Drug Administration

Additional relevant MeSH terms:


Leukemia, Lymphoid Lymphoma Lymphoma, Extranodal NK-T-Cell Lymphoma, Large B-Cell, Diffuse Lymphoma, Large-Cell, Immunoblastic Lymphomatoid Granulomatosis Lymphoproliferative Disorders Precursor Cell Lymphoblastic Leukemia-Lymphoma Immune System Diseases Immunoproliferative Disorders Leukemia Lymphatic Diseases Lymphoma, B-Cell Lymphoma, Non-Hodgkin Lymphoma, T-Cell	Neoplasms Neoplasms by Histologic Type Precancerous Conditions Antibodies, Monoclonal Cyclosporine Cyclosporins Fludarabine Fludarabine phosphate Mycophenolate mofetil Mycophenolic Acid Rituximab Anti-Infective Agents Antibiotics, Antineoplastic Antifungal Agents Antimetabolites

ClinicalTrials.gov processed this record on March 03, 2015