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

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01434472
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 20
• Location: 1
• Arm: 1
• Actual Duration (Months): 101.7
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

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 or Disease	Intervention/Treatment	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; Drug: Fludarabine	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (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
• Actual Study Start Date: Nov 16, 2011
• Actual Primary Completion Date: May 6, 2020
• Actual Study Completion Date: May 6, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: 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).

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: 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 ; Radiation: Total-Body Irradiation; Undergo TBI; Other Names: TOTAL BODY IRRADIATION Whole-Body Irradiation TBI 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 ; Drug: Fludarabine; Given IV; Other Names: 118218 2-Fluoro-9-beta-arabinofuranosyladenine 2-Fluorovidarabine 9-Beta-D-arabinofuranosyl-2-fluoro-9H-purin-6-amine Fluradosa

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival [1 year]

   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 progression-free survival of this highest-risk group of patients is 54% or greater.

Secondary Outcome Measures

1. Absolute Neutrophil Count (ANC) Engraftment [Up to day 100]

   The median time in days to achieve ANC recovery defined as ANC>500uL.

2. Overall Survival [Up to 2 years post transplant]

3. Response Rates [Day 100]

   Response is defined as having achieved a Partial Response or better.

4. Treatment-related Mortality [Day 100]

   Defined as death in the absence of progressive lymphoma that can be possibly, probably, or definitely attributed to the radioimmunotherapy.

5. Platelet Engraftment [Up to day 100]

   The median time in days to achieve platelet recovery as defined as platelet >20,000uL.

6. Hematopoietic Toxicity [Up to day 100]

   Clinical sequelae due to hematopoietic toxicity as defined by incidences of neutropenic fever and bleeding.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109

Sponsors and Collaborators

• Fred Hutchinson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Ajay Gopal, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 7, 2020

More Information

Publications

None provided.

• Responsible Party: Ajay Gopal, Professor, Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT01434472
• Other Study ID Numbers: 2398.00; NCI-2011-01189; 2398.00; P01CA044991; P30CA015704; RG9213033
• First Posted: Sep 15, 2011
• Last Update Posted: Jul 20, 2021
• Last Verified: Jul 1, 2021

• Additional relevant MeSH terms: Burkitt Lymphoma; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Large B-Cell, Diffuse; Lymphoproliferative Disorders; Recurrence; Vidarabine; Cyclosporine; Mycophenolic Acid; Rituximab; Antineoplastic Agents, Immunological; Fludarabine; Fludarabine phosphate; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Cyclosporins

Study Results

Participant Flow

Arm/Group Title	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT)
Arm/Group Description	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). Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter) Cyclosporine: Given PO Fludarabine Phosphate: Given IV Indium In-111 Ibritumomab Tiuxetan: Given IV Mycophenolate Mofetil: Given PO Pharmacological Study: Correlative studies Rituximab: Given IV prior to yttrium Y 90 ibritumomab tiuxetan Total-Body Irradiation: Undergo TBI Yttrium Y-90 Ibritumomab Tiuxetan: Given IV Fludarabine: Given IV
Period Title: Overall Study
STARTED	20
COMPLETED	20
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT)
Arm/Group Description	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). Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter) Cyclosporine: Given PO Fludarabine Phosphate: Given IV Indium In-111 Ibritumomab Tiuxetan: Given IV Mycophenolate Mofetil: Given PO Pharmacological Study: Correlative studies Rituximab: Given IV prior to yttrium Y 90 ibritumomab tiuxetan Total-Body Irradiation: Undergo TBI Yttrium Y-90 Ibritumomab Tiuxetan: Given IV Fludarabine: Given IV
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	19 95%
>=65 years	1 5%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	52.5
Sex: Female, Male (Count of Participants)
Female	7 35%
Male	13 65%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	20 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	4 20%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	16 80%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival
Description	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 progression-free survival of this highest-risk group of patients is 54% or greater.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT)
Arm/Group Description	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). Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter) Cyclosporine: Given PO Fludarabine Phosphate: Given IV Indium In-111 Ibritumomab Tiuxetan: Given IV Mycophenolate Mofetil: Given PO Pharmacological Study: Correlative studies Rituximab: Given IV prior to yttrium Y 90 ibritumomab tiuxetan Total-Body Irradiation: Undergo TBI Yttrium Y-90 Ibritumomab Tiuxetan: Given IV Fludarabine: Given IV
Measure Participants	20
Count of Participants [Participants]	11 55%

2. Secondary Outcome

Title	Absolute Neutrophil Count (ANC) Engraftment
Description	The median time in days to achieve ANC recovery defined as ANC>500uL.
Time Frame	Up to day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT)
Arm/Group Description	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). Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter) Cyclosporine: Given PO Fludarabine Phosphate: Given IV Indium In-111 Ibritumomab Tiuxetan: Given IV Mycophenolate Mofetil: Given PO Pharmacological Study: Correlative studies Rituximab: Given IV prior to yttrium Y 90 ibritumomab tiuxetan Total-Body Irradiation: Undergo TBI Yttrium Y-90 Ibritumomab Tiuxetan: Given IV Fludarabine: Given IV
Measure Participants	20
Median (Full Range) [Days]	16

3. Secondary Outcome

Title	Overall Survival
Time Frame	Up to 2 years post transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT)
Arm/Group Description	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). Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter) Cyclosporine: Given PO Fludarabine Phosphate: Given IV Indium In-111 Ibritumomab Tiuxetan: Given IV Mycophenolate Mofetil: Given PO Pharmacological Study: Correlative studies Rituximab: Given IV prior to yttrium Y 90 ibritumomab tiuxetan Total-Body Irradiation: Undergo TBI Yttrium Y-90 Ibritumomab Tiuxetan: Given IV Fludarabine: Given IV
Measure Participants	20
Count of Participants [Participants]	14 70%

4. Secondary Outcome

Title	Response Rates
Description	Response is defined as having achieved a Partial Response or better.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT)
Arm/Group Description	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). Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter) Cyclosporine: Given PO Fludarabine Phosphate: Given IV Indium In-111 Ibritumomab Tiuxetan: Given IV Mycophenolate Mofetil: Given PO Pharmacological Study: Correlative studies Rituximab: Given IV prior to yttrium Y 90 ibritumomab tiuxetan Total-Body Irradiation: Undergo TBI Yttrium Y-90 Ibritumomab Tiuxetan: Given IV Fludarabine: Given IV
Measure Participants	20
Count of Participants [Participants]	16 80%

5. Secondary Outcome

Title	Treatment-related Mortality
Description	Defined as death in the absence of progressive lymphoma that can be possibly, probably, or definitely attributed to the radioimmunotherapy.
Time Frame	Day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT)
Arm/Group Description	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). Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter) Cyclosporine: Given PO Fludarabine Phosphate: Given IV Indium In-111 Ibritumomab Tiuxetan: Given IV Mycophenolate Mofetil: Given PO Pharmacological Study: Correlative studies Rituximab: Given IV prior to yttrium Y 90 ibritumomab tiuxetan Total-Body Irradiation: Undergo TBI Yttrium Y-90 Ibritumomab Tiuxetan: Given IV Fludarabine: Given IV
Measure Participants	20
Count of Participants [Participants]	1 5%

6. Secondary Outcome

Title	Platelet Engraftment
Description	The median time in days to achieve platelet recovery as defined as platelet >20,000uL.
Time Frame	Up to day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT)
Arm/Group Description	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). Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter) Cyclosporine: Given PO Fludarabine Phosphate: Given IV Indium In-111 Ibritumomab Tiuxetan: Given IV Mycophenolate Mofetil: Given PO Pharmacological Study: Correlative studies Rituximab: Given IV prior to yttrium Y 90 ibritumomab tiuxetan Total-Body Irradiation: Undergo TBI Yttrium Y-90 Ibritumomab Tiuxetan: Given IV Fludarabine: Given IV
Measure Participants	20
Median (Full Range) [Days]	9

7. Secondary Outcome

Title	Hematopoietic Toxicity
Description	Clinical sequelae due to hematopoietic toxicity as defined by incidences of neutropenic fever and bleeding.
Time Frame	Up to day 100

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT)
Arm/Group Description	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). Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter) Cyclosporine: Given PO Fludarabine Phosphate: Given IV Indium In-111 Ibritumomab Tiuxetan: Given IV Mycophenolate Mofetil: Given PO Pharmacological Study: Correlative studies Rituximab: Given IV prior to yttrium Y 90 ibritumomab tiuxetan Total-Body Irradiation: Undergo TBI Yttrium Y-90 Ibritumomab Tiuxetan: Given IV Fludarabine: Given IV
Measure Participants	20
Number [Incidences]	5

Adverse Events

Time Frame	AEs will be collected from the time of first exposure to a study intervention (i.e., the start of the rituximab infusion associated with the therapy dose) through day +100 post-transplant or through discharge prior to that date from the SCCA system to care of the patient's primary physician.
Arm/Group Title	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT)
Arm/Group Description	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). Allogeneic Hematopoietic Stem Cell Transplantation: Undergo allogeneic PBSCT (infusion of donor stem cells via central catheter) Cyclosporine: Given PO Fludarabine Phosphate: Given IV Indium In-111 Ibritumomab Tiuxetan: Given IV Mycophenolate Mofetil: Given PO Pharmacological Study: Correlative studies Rituximab: Given IV prior to yttrium Y 90 ibritumomab tiuxetan Total-Body Irradiation: Undergo TBI Yttrium Y-90 Ibritumomab Tiuxetan: Given IV Fludarabine: Given IV
All Cause Mortality
	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT)
	Affected / at Risk (%)	# Events
Total	6/20 (30%)
Serious Adverse Events
	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT)
	Affected / at Risk (%)	# Events
Total	11/20 (55%)
Gastrointestinal disorders
Abdominal Pain	2/20 (10%)	2
Diarrhea	2/20 (10%)	3
Enterocolitis	1/20 (5%)	1
Infections and infestations
Wound Infection	1/20 (5%)	1
E. coli bacteremia	1/20 (5%)	1
Blood infection	2/20 (10%)	2
Neutropenic fever	3/20 (15%)	5
Investigations
Acute Renal Injury	2/20 (10%)	2
Nervous system disorders
Dizziness	1/20 (5%)	1
Extrapyramidal disorder	1/20 (5%)	1
Respiratory, thoracic and mediastinal disorders
Adenovirus pneumonia	1/20 (5%)	1
ARDS	1/20 (5%)	2
Ascites	1/20 (5%)	1
Hypoxia	1/20 (5%)	1
Vascular disorders
Thromboembolic event - cerebal infarct	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Radiolabeled Antibody, TBI, Allogeneic PBSCT)
	Affected / at Risk (%)	# Events
Total	11/20 (55%)
Gastrointestinal disorders
Anorexia	2/20 (10%)	2
General disorders
Fatigue	3/20 (15%)	3
Metabolism and nutrition disorders
Hypophosphatemia	4/20 (20%)	4
Skin and subcutaneous tissue disorders
Rash	5/20 (25%)	5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.