NCT01921387

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

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

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 20 (actual)
• Sponsor: Fred Hutchinson Cancer Center · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

Conditions

• 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

Interventions

Type	Name	Description
PROCEDURE	Autologous Hematopoietic Stem Cell Transplantation	Undergo autologous PBSC transplant
DRUG	Carmustine	Given IV
DRUG	Cytarabine	Given IV
DRUG	Etoposide	Given IV
OTHER	Laboratory Biomarker Analysis	Correlative studies
DRUG	Melphalan	Given IV
PROCEDURE	Peripheral Blood Stem Cell Transplantation	Undergo autologous PBSC transplant
RADIATION	Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8	Given IV

Timeline

• Start date: 2013-10-09
• Primary completion: 2017-07-26
• Completion: 2020-07-26
• First posted: 2013-08-13
• Last updated: 2020-08-04
• Results posted: 2018-09-04

Locations

1 site across 1 country: United States