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

Phase 1

Completed

• Conditions: Refractory Hodgkin Lymphoma; Recurrent Hodgkin Lymphoma; Refractory T-Cell Non-Hodgkin Lymphoma; Recurrent B-Cell Non-Hodgkin Lymphoma; Recurrent T-Cell Non-Hodgkin Lymphoma; Refractory Mantle Cell Lymphoma; Recurrent Mantle Cell Lymphoma; Refractory B-Cell Non-Hodgkin Lymphoma
• 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

• Registration Number: NCT01921387
• Lead Sponsor: Fred Hutchinson Cancer Center

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, c...

Detailed Description

PRIMARY OBJECTIVES:
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Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2013-08-09
• Study First Submitted QC: 2013-08-12
• Study First Posted: 2013-08-13
• Study Start: 2013-10-09
• Primary Completion: 2017-07-26
• Results First Submitted: 2018-07-30
• Results First Submitted QC: 2018-08-30
• Results First Posted: 2018-09-04
• Status Verified: 2020-07
• Study Completion: 2020-07-26
• Last Update Submitted: 2020-07-29
• Last Update Posted: 2020-08-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 20

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)	Laboratory Biomarker Analysis	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.
Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)	Autologous Hematopoietic Stem Cell Transplantation	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.
Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)	Peripheral Blood Stem Cell Transplantation	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.
Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)	Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8	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.
Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)	Carmustine	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.
Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)	Cytarabine	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.
Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)	Etoposide	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.
Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)	Melphalan	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.

Primary Outcome Measures

Name	Time	Method
Maximum-tolerated Dose (MTD) of Yttrium-90-BC8-DOTA	Within 30 days post-transplant	Single patients will be treated at escalating doses in 2-Gy increments (Table 4) until a DLT is observed. Once a DLT is observed, the second stage will begin at the next lower dose level and patients will be treated in cohorts of 4.
Progression-free Survival Following Autologous Stem Cell Transplant (ASCT)	1 year	Estimate the 1 year progression-free survival (PFS) rate after ASCT

Secondary Outcome Measures

Name	Time	Method
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	Up to 5 years	Will be evaluated among all patients and among those treated at the estimated MTD.
The Lowest Antibody (Yttrium 90-BC8-DOTA) Dose (mg/kg) That is Consistent With a Favorable Biodistribution Rate >= 80% in Lymphoma Patients	Up to 5 years

Trial Locations

Locations (1)

Fred Hutch/University of Washington Cancer Consortium; 🇺🇸 Seattle, Washington, United States