Anti-CD20 Radioimmunotherapy Before Chemotherapy and Stem Cell Transplant in Treating Patients With High-Risk B-Cell Malignancies

• Sponsor: Fred Hutchinson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02483000
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 3
• Location: 1
• Arm: 1
• Actual Duration (Months): 43
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase I/II trial studies the side effects and best dose of anti-cluster of differentiation (CD)20 radioimmunotherapy (RIT), and to see how well it works when given before chemotherapy and stem cell transplant in treating patients with B-cell malignancies that have not responded to treatment or have come back after responding to treatment. CD20 is a protein found on the cells of a type of cancer cell called B-cells. Anti-CD20 RIT attaches radioactive material to a drug that is designed to target CD20, which brings radioactive material to the cancer cells to kill the cells. This may kill more tumor cells while causing fewer side effects to healthy tissue. Adding anti-CD20 to standard chemotherapy and stem cell transplant may be more effective in treating patients with B-cell malignancies.

Condition or Disease	Intervention/Treatment	Phase
Burkitt Lymphoma; CD20-Positive Neoplastic Cells Present; Diffuse Large B-Cell Lymphoma; Indolent Non-Hodgkin Lymphoma; Mantle Cell Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Refractory Mature B-Cell Non-Hodgkin Lymphoma	Biological: Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Carmustine; Drug: Clearing Agent; Drug: Cytarabine; Drug: Etoposide; Radiation: Indium In 111-DOTA-Biotin; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Pharmacological Study; Radiation: Yttrium Y 90-DOTA-Biotin	Phase 1

Detailed Description

PRIMARY OBJECTIVES:

1. To estimate the maximum tolerated dose (MTD) of 90Y activity that can be delivered via pretargeted radioimmunotherapy (PRIT) using B9E9-fusion protein (B9E9-FP), clearing agent (CA), and radiolabeled tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin when followed by carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy and autologous stem cell transplantation.

SECONDARY OBJECTIVES:

1. To assess the overall and progression-free survival of the above regimen in such patients.

2. To evaluate the response rates of the above therapy.

3. To evaluate the toxicity and tolerability of the above therapy.

4. To evaluate the feasibility of delivering sequential high-dose PRIT and chemotherapy.

TERTIARY OBJECTIVES:

1. Assess biodistribution and pharmacokinetics of B9E9-FP and radiolabeled DOTA-Biotin.

2. Assess ability of the clearing agent (CA) to remove excess B9E9-FP from the serum.

3. Evaluate the impact, if any, of circulating rituximab on biodistributions.

OUTLINE: This is a phase I, dose-escalation study of yttrium Y 90 DOTA-biotin followed by a phase II study.

B9E9-FP INFUSION: Patients receive B9E9-fusion protein intravenously (IV) over a minimum of 2 hours on day -17.

CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15.

RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14.

BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours twice daily (BID) and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2.

STEM CELL INFUSION: Patients undergo autologous peripheral blood stem cell transplant (PBSCT) on day 0 per standard of care.

After completion of study treatment, patients are followed up at 1, 3, 6, and 12 months, and then annually thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 3 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Evaluation of Pretargeted Anti-CD20 Radioimmunotherapy Combined With BEAM Chemotherapy and Autologous Stem Cell Transplantation for High-Risk B-Cell Malignancies
• Actual Study Start Date: Feb 1, 2017
• Actual Primary Completion Date: Nov 17, 2019
• Actual Study Completion Date: Sep 2, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Treatment (PRIT) B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care.

Biological: Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein; Given IV; Other Names: Anti-CD20 B9E9 scFv-SA Fusion Protein Anti-CD20 B9E9-SA Fusion Protein B9E9 scFvSA Fusion Protein Recombinant Anti-CD20 B9E9 scFvSA Fusion Protein scFv B9E9-streptavidin Fusion Protein ; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Undergo autologous PBSCT; Other Names: Autologous Stem Cell Transplantation ; Drug: Carmustine; Given IV; Other Names: BCNU Becenum Becenun BiCNU Bis(chloroethyl) Nitrosourea Bis-Chloronitrosourea Carmubris Carmustin Carmustinum FDA 0345 Gliadel N,N'-Bis(2-chloroethyl)-N-nitrosourea Nitrourean Nitrumon SK 27702 SRI 1720 WR-139021 ; Drug: Clearing Agent; Given IV; Drug: Cytarabine; Given IV; Other Names: .beta.-Cytosine arabinoside 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-.beta.-D-Arabinofuranosylcytosine 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone 1-Beta-D-arabinofuranosylcytosine 1.beta.-D-Arabinofuranosylcytosine 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl- 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl- Alexan Ara-C ARA-cell Arabine Arabinofuranosylcytosine Arabinosylcytosine Aracytidine Aracytin Aracytine Beta-Cytosine Arabinoside CHX-3311 Cytarabinum Cytarbel Cytosar Cytosar-U Cytosine Arabinoside Cytosine-.beta.-arabinoside Cytosine-beta-arabinoside Erpalfa Starasid Tarabine PFS U 19920 U-19920 Udicil WR-28453 ; Drug: Etoposide; Given IV; Other Names: Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 ; Radiation: Indium In 111-DOTA-Biotin; Given IV; Other Names: In 111-DOTA-Biotin ; Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Melphalan; Given IV; Other Names: Alanine Nitrogen Mustard CB-3025 L-PAM L-Phenylalanine Mustard L-Sarcolysin L-Sarcolysin Phenylalanine mustard L-Sarcolysine Melphalanum Phenylalanine Mustard Phenylalanine Nitrogen Mustard Sarcoclorin Sarkolysin WR-19813 ; Procedure: Peripheral Blood Stem Cell Transplantation; Undergo autologous PBSCT; Other Names: PBPC transplantation PBSCT Peripheral Blood Progenitor Cell Transplantation Peripheral Stem Cell Support Peripheral Stem Cell Transplant Peripheral Stem Cell Transplantation ; Other: Pharmacological Study; Correlative studies; Radiation: Yttrium Y 90-DOTA-Biotin; Given IV; Other Names: 90Y-DOTA-Biotin yttrium Y 90 DOTA-biotin

Outcome Measures

Primary Outcome Measures

1. Maximum Tolerated Dose (MTD) of Yttrium Y 90 DOTA-biotin Defined as the Dose That is Associated With a True Dose Limiting Toxicity (DLT) Rate of 25%, Where a DLT is Defined as a Therapy-related Grade III or IV Bearman (Transplant) Toxicity [Up to 30 days after transplant]

   Following the completed observation of the final patient, a two-parameter logistic model will be fit to the data, thereby generating a dose-toxicity curve based on the observed DLT rate at the various dose levels visited. Based on this fitted model, the MTD is estimated to be the dose that is associated with a DLT rate of 25%.

Secondary Outcome Measures

1. Dosimetry of Yttrium Y 90 DOTA-biotin [Up to 7 days after infusion]

   Assessed using OLINDA dosimetry software. The estimated dose to normal organs and tumor sites will be described based on the tumor to normal organ ratios derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of yttrium Y 90 DOTA-biotin.

2. Incidence of Toxicity, Defined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0 [Up to 30 days after transplant]

   Descriptive statistics on the number and percent toxicities will be calculated.

3. Overall Response Rate [Up to 4 years]

   Descriptive statistics on the responses will be calculated.

4. Overall Survival [Up to 4 years]

   Overall survival will be estimated.

5. Progression Free Survival (PFS) [1 year from autologous stem cell transplant]

   If the true 1-year PFS rate using the proposed approach is 54%, then 24 patients will provide 80% power to detect a statistically significant increased rate of PFS from the fixed rate of 30%, based on a one-sample chi-square test with one-sided significance level of 5%.

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 lymphoma expressing the CD20 antigen and generally must have failed at least one prior standard systemic therapy; the exception will be mantle cell lymphoma (MCL) patients, who may be enrolled while in first complete remission (CR) as well as other select high-risk lymphomas (e.g., Burkitt?s, double hit diffuse large B-cell lymphoma [DLBCL], transformed indolent B-cell non-Hodgkin lymphoma [B-NHL], etc.) in accordance with current transplant standard of care for these patients

• 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

• All patients eligible for therapeutic study must have (>= 2 x 10^6 CD34/kg) autologous hematopoietic stem cells harvested and cryopreserved

• Patients must have an expected survival of > 60 days and must be free of major infection

• Patients of childbearing potential must agree to abstinence or the use of effective contraception

• DONOR SELECTION: Not applicable; this protocol employs autologous transplantation, utilizing the patient?s own hematopoietic stem cells obtained from either the peripheral blood or bone marrow

Exclusion Criteria:

• Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled 90Y therapy dose

• Inability to understand or give an informed consent

• Prior radiation > 20 Gy to any critical normal organ (e.g., lung, liver, spinal cord, both kidneys) within 1 year of the treatment date

• Active central nervous system lymphoma

• Other serious medical conditions considered to represent contraindications to bone marrow transplant (BMT) (e.g., abnormally decreased cardiac ejection fraction, diffusion capacity of the lung for carbon monoxide [DLCO] < 50% predicted, patient on supplemental oxygen, acquired immune deficiency syndrome [AIDS], etc.)

• Pregnancy or breast feeding

• Prior bone marrow or stem cell transplant

• Southwest Oncology Group (SWOG) performance status >= 2.0

• Known sensitivity to kanamycin and other aminoglycosides; patients with known hypersensitivity to kanamycin or any other aminoglycoside antibiotic will be excluded

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 24, 2017

More Information

Publications

None provided.

• Responsible Party: Fred Hutchinson Cancer Center
• ClinicalTrials.gov Identifier: NCT02483000
• Other Study ID Numbers: 9189; NCI-2015-00299; 9189; P01CA044991; P30CA015704
• First Posted: Jun 26, 2015
• Last Update Posted: Nov 23, 2020
• Last Verified: Sep 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Burkitt Lymphoma; Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, B-Cell; Lymphoma, Mantle-Cell; Lymphoma, Large B-Cell, Diffuse; Biotin; Cytarabine; Etoposide; Podophyllotoxin; Etoposide phosphate; Melphalan; Mechlorethamine; Carmustine; Nitrogen Mustard Compounds; 1,4,7,10-tetraazacyclododecane- 1,4,7,10-tetraacetic acid

Study Results

Participant Flow

Arm/Group Title	Treatment (PRIT)
Arm/Group Description	B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care. Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein: Given IV Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSCT
Period Title: Overall Study
STARTED	3
COMPLETED	3
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (PRIT)
Arm/Group Description	B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care. Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein: Given IV Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSCT
Overall Participants	3
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	3 100%
>=65 years	0 0%
Age (Years) [Mean (Full Range) ]
Mean (Full Range) [Years]	58
Sex: Female, Male (Count of Participants)
Female	1 33.3%
Male	2 66.7%
Race/Ethnicity, Customized (Count of Participants)
Non-Hispanic	3 100%
White	3 100%
Region of Enrollment (participants) [Number]
United States	3 100%

Outcome Measures

1. Primary Outcome

Title	Maximum Tolerated Dose (MTD) of Yttrium Y 90 DOTA-biotin Defined as the Dose That is Associated With a True Dose Limiting Toxicity (DLT) Rate of 25%, Where a DLT is Defined as a Therapy-related Grade III or IV Bearman (Transplant) Toxicity
Description	Following the completed observation of the final patient, a two-parameter logistic model will be fit to the data, thereby generating a dose-toxicity curve based on the observed DLT rate at the various dose levels visited. Based on this fitted model, the MTD is estimated to be the dose that is associated with a DLT rate of 25%.
Time Frame	Up to 30 days after transplant

Outcome Measure Data

Analysis Population Description

This outcome measure was not done. The starting dose level was level 1 (30 mCi/m2) and in the first stage, up to two patients would be treated at escalating doses in 20 mCi/m2 increments until a DLT was observed. With the 3 participants enrolled, only dose level 5 of 12 was achieved before the study was closed early. The Maximum Tolerated Dose was not determined due to small sample size.

Arm/Group Title	Treatment (PRIT)
Arm/Group Description	B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care. Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein: Given IV Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSCT
Measure Participants	0

2. Secondary Outcome

Title	Dosimetry of Yttrium Y 90 DOTA-biotin
Description	Assessed using OLINDA dosimetry software. The estimated dose to normal organs and tumor sites will be described based on the tumor to normal organ ratios derived from dosimetry estimates coupled with the absorbed dose to normal organs based on the administered activity of yttrium Y 90 DOTA-biotin.
Time Frame	Up to 7 days after infusion

Outcome Measure Data

Analysis Population Description

Absorbed dose in target organs.

Arm/Group Title	Treatment (PRIT)
Arm/Group Description	B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care. Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein: Given IV Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSCT
Measure Participants	3
Liver	2.5
Spleen	3.73
Lungs	0.229
Kidneys	11.4
Bone Marrow	3.75
Brain	0.229

3. Secondary Outcome

Title	Incidence of Toxicity, Defined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
Description	Descriptive statistics on the number and percent toxicities will be calculated.
Time Frame	Up to 30 days after transplant

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (PRIT)
Arm/Group Description	B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care. Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein: Given IV
Measure Participants	3
Serious Adverse Events	2 66.7%
Other (Not Including Serious) Adverse Events	2 66.7%

4. Secondary Outcome

Title	Overall Response Rate
Description	Descriptive statistics on the responses will be calculated.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (PRIT)
Arm/Group Description	B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care.
Measure Participants	3
Participants who achieved a CR	2 66.7%
Participants who achieved a PR	1 33.3%

5. Secondary Outcome

Title	Overall Survival
Description	Overall survival will be estimated.
Time Frame	Up to 4 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (PRIT)
Arm/Group Description	B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care. Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein: Given IV Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSCT
Measure Participants	3
Count of Participants [Participants]	2 66.7%

6. Secondary Outcome

Title	Progression Free Survival (PFS)
Description	If the true 1-year PFS rate using the proposed approach is 54%, then 24 patients will provide 80% power to detect a statistically significant increased rate of PFS from the fixed rate of 30%, based on a one-sample chi-square test with one-sided significance level of 5%.
Time Frame	1 year from autologous stem cell transplant

Outcome Measure Data

Analysis Population Description

This outcome measure was not done since 24 patients were needed to provide 80% power to detect statistical significance. The sample size of 3 patients is too small to determine the true 1-year PFS rate.

Arm/Group Title	Treatment (PRIT)
Arm/Group Description	B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2.
Measure Participants	0

Adverse Events

Time Frame	AEs will be collected from the time of first exposure to an investigational agent through the start of BEAM chemotherapy treatment all SAEs and all grades of adverse events will be captured. From the start of BEAM chemotherapy through day +30 post-transplant non-hematologic adverse events of ≥ grade 3, and all serious adverse events will be captured. Beyond day +30 after transplant/discharge from the transplant service until day +100, only SAEs and grade 4 and 5 toxicities will be collected.
Arm/Group Title	Treatment (PRIT)
Arm/Group Description	B9E9-FP INFUSION: Patients receive B9E9-fusion protein IV over a minimum of 2 hours on day -17. CLEARING AGENT INFUSION: Patients receive clearing agent IV over a minimum of 30 minutes on day -15. RADIOBIOTIN INFUSION: Patients receive indium In 111-DOTA-biotin IV and yttrium Y 90 DOTA-biotin IV over 2-5 minutes on day -14. BEAM CHEMOTHERAPY: Patients receive BEAM chemotherapy comprising carmustine IV over 3 hours on day -7; etoposide IV over 2 hours BID and cytarabine IV over 4 hours BID on days -6 to -3; and melphalan IV over 30 minutes on day -2. STEM CELL INFUSION: Patients undergo autologous PBSCT on day 0 per standard of care. Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein: Given IV Autologous Hematopoietic Stem Cell Transplantation: Undergo autologous PBSCT
All Cause Mortality
	Treatment (PRIT)
	Affected / at Risk (%)	# Events
Total	1/3 (33.3%)
Serious Adverse Events
	Treatment (PRIT)
	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)
Blood and lymphatic system disorders
Febrile Neutropenia	2/3 (66.7%)	2
Gastrointestinal disorders
Diarrhea	1/3 (33.3%)	1
Mucositis, Oral	2/3 (66.7%)	2
Other (Not Including Serious) Adverse Events
	Treatment (PRIT)
	Affected / at Risk (%)	# Events
Total	2/3 (66.7%)
Gastrointestinal disorders
Diarrhea	1/3 (33.3%)	1
Skin and subcutaneous tissue disorders
Rash maculo-papular	1/3 (33.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.