Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies

Tracking Information
First Submitted Date ICMJE	August 9, 2013
First Posted Date ICMJE	August 13, 2013
Last Update Posted Date	May 24, 2018
Actual Study Start Date ICMJE	October 9, 2013
Actual Primary Completion Date	July 26, 2017 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: July 18, 2017)	Maximum-tolerated dose (MTD) of yttrium Y 90 anti-CD45 monoclonal antibody BC8, defined as the dose that is associated with a true dose-limiting toxicity (DLT) rate of 25% [ Time Frame: Within 30 days post-transplant ]DLT is defined as a therapy-related grade III or IV Bearman (transplant) toxicity.; Progression-free survival following autologous stem cell transplant (ASCT) [ Time Frame: 1 year ]Will be compared to a historical control.
Original Primary Outcome Measures ICMJE; (submitted: August 12, 2013)	Dose-limiting toxicities defined as therapy-related grade III or IV Bearman scale (transplant) toxicity [ Time Frame: Within 30 days post-transplant ]; Progression-free survival (PFS) following ASCT [ Time Frame: 1 year ]
Change History	Complete list of historical versions of study NCT01921387 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: July 18, 2017)	Estimated dose to tumor sites 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 anti-CD45 monoclonal antibody BC8 [ Time Frame: Up to 5 years ]Will be evaluated among all patients and among those treated at the estimated MTD.; The lowest antibody (yttrium Y 90 anti-CD45 monoclonal antibody BC8) dose (mg/kg) that is consistent with a favorable biodistribution rate >= 80% in lymphoma patients [ Time Frame: Up to 5 years ]A favorable biodistribution in a given patient will be defined by the target tissue receiving higher radiation dose per unit-administered activity (cGy/mCi) relative to all critical normal organs (lung, liver, kidney, etc.).
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Radiolabeled Monoclonal Antibody and Combination Chemotherapy Before Stem Cell Transplant in Treating Patients With High-Risk Lymphoid Malignancies
Official Title ICMJE	A Phase I/II Study Evaluating Escalating Doses of 90Y-BC8-DOTA (Anti-CD45) Antibody Followed by BEAM Chemotherapy and Autologous Stem Cell Transplantation for High-Risk Lymphoid Malignancies
Brief Summary	This phase I/II trial studies the side effects and the best dose of radiolabeled monoclonal antibody when given together with combination chemotherapy before stem cell transplant and to see how well it works in treating patients with high-risk lymphoid malignancies. Radiolabeled monoclonal antibodies, such as yttrium Y 90 anti-CD45 monoclonal antibody BC8, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving chemotherapy before a stem transplant stops the growth of cancer cells by stopping them from dividing or killing them. Stem cells collected from the patient's blood are then returned to the patient to replace the blood-forming cells that were destroyed by the radiolabeled monoclonal antibody and chemotherapy.
Detailed Description	PRIMARY OBJECTIVES: I. To estimate the maximum-tolerated dose (MTD) of 90Y-BC8-DOTA (yttrium Y 90 anti-CD45 monoclonal antibody BC8) (anti-cluster of differentiation [CD] 45) that can be delivered prior to myeloablative carmustine, etoposide, cytarabine, and melphalan (BEAM) chemotherapy and autologous stem cell transplant (ASCT) for patients with high-risk B-non-Hodgkin lymphoma (NHL), T-NHL, and Hodgkin lymphoma (HL). II. To evaluate the efficacy of 90Y-BC8-DOTA when administered at the estimated MTD prior to BEAM chemotherapy and ASCT for patients with high-risk B-NHL, T-NHL, and HL compared to historical controls treated with BEAM alone. SECONDARY OBJECTIVES: I. To describe the toxicity observed from the addition of 90Y-BC8-DOTA to BEAM. II. To optimize the protein dose (Ab) to deliver a favorable biodistribution in the majority of patients. III. To describe response rates and overall survival of patients with high-risk B-NHL, T-NHL, and HL following administration of 90Y-BC8-DOTA plus BEAM prior to ASCT. IV. To describe the impact of rituximab concentrations, B-cell depletion, and disease burden on CD45 targeting. V. To assess the correlation of lymphoma biomarkers with outcomes. VI. To evaluate the effects of nodal-targeted irradiation by 90Y-BC8-DOTA on immune reconstitution following ASCT. OUTLINE: This is a phase I, dose-escalation study of yttrium Y 90 anti-CD45 monoclonal antibody BC8 followed by a phase II study. Patients receive yttrium Y 90 anti-CD45 monoclonal antibody BC8 intravenously (IV) on day -14. Patients also receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours twice daily (BID) on days -6 to -3, cytarabine IV over 4 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2. Patients then undergo autologous peripheral blood stem cell (PBSC) transplant on day 0. After completion of study treatment, patients are followed up at 3, 6, and 12 months and then annually thereafter.
Study Type ICMJE	Interventional
Study Phase	Phase 1; Phase 2
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma; Refractory Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma
Intervention ICMJE	Procedure: Autologous Hematopoietic Stem Cell Transplantation Undergo autologous PBSC transplant Other Name: 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: 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; 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 PBSC transplant Other Names: PBPC transplantation PBSCT Peripheral Blood Progenitor Cell Transplantation Peripheral Stem Cell Support Peripheral Stem Cell Transplant Peripheral Stem Cell Transplantation; Radiation: Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 Given IV Other Name: 90Y Anti-CD45 MoAb BC8
Study Arms	Experimental: Treatment (90Y-BC8-DOTA, chemotherapy, PBSC); Patients receive yttrium Y 90 anti-CD45 monoclonal antibody BC8 IV on day -14. Patients also receive carmustine IV over 3 hours on day -7, etoposide IV over 2 hours BID on days -6 to -3, cytarabine IV over 4 hours BID on days -6 to -3, and melphalan IV over 30 minutes on day -2. Patients then undergo autologous PBSC transplant on day 0.; Interventions: Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Carmustine; Drug: Cytarabine; Drug: Etoposide; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Procedure: Peripheral Blood Stem Cell Transplantation; Radiation: Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8
Publications *	Not Provided
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Active, not recruiting
Actual Enrollment ICMJE; (submitted: August 7, 2017)	21
Original Estimated Enrollment ICMJE; (submitted: August 12, 2013)	70
Estimated Study Completion Date	July 26, 2021
Actual Primary Completion Date	July 26, 2017 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Patients must have a histologically confirmed diagnosis of B-NHL, T-NHL, or HL; only patients with classical HL must have documented histologic demonstration of CD45+ cells adjacent to the Reed Sternberg cells; patients must have received at least one prior standard systemic therapy with documented recurrent or refractory disease; patients with mantle cell lymphoma (MCL), T-NHL, or other high-risk malignancies may be enrolled/transplanted in complete remission (CR)/first partial remission (PR1); Creatinine < 2.0; Bilirubin < 1.5 mg/dL; All patients eligible for therapeutic study must have a minimum of >= 2 x10^6 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 Exclusion Criteria: Circulating human anti-mouse antibody (HAMA), to be determined before each infusion; Systemic anti-lymphoma therapy given in the previous 30 days before the scheduled therapy dose with the exception of rituximab; Inability to understand or give an informed consent; Lymphoma involving the central nervous system; Other serious medical conditions considered to represent contraindications to ASCT (e.g., abnormally decreased cardiac ejection fraction, diffusion capacity of carbon monoxide [DLCO] < 50% predicted, etc.); Known human immunodeficiency virus (HIV) seropositivity; Pregnancy or breast feeding; Prior autologous or allogeneic bone marrow or stem cell transplant; Prior radiation therapy (RT) > 20 gray (Gy) to a critical organ within 1 year of enrollment; Southwestern Oncology Group (SWOG) performance status >= 2.0
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01921387
Other Study ID Numbers ICMJE	2728.00; NCI-2013-01378 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); 2728.00 ( Other Identifier: Fred Hutch/University of Washington Cancer Consortium ); P01CA044991 ( U.S. NIH Grant/Contract ); P30CA015704 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Fred Hutchinson Cancer Research Center
Study Sponsor ICMJE	Fred Hutchinson Cancer Research Center
Collaborators ICMJE	National Cancer Institute (NCI)
Investigators ICMJE	Principal Investigator: Ajay Gopal Fred Hutch/University of Washington Cancer Consortium
PRS Account	Fred Hutchinson Cancer Research Center
Verification Date	May 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP