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

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

20 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-10-09

Study Completion Date

2020-07-26

Brief Summary

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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.

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Detailed Description

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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

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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

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Autologous Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo autologous PBSC transplant

Carmustine

Intervention Type DRUG

Given IV

Cytarabine

Intervention Type DRUG

Given IV

Etoposide

Intervention Type DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type OTHER

Correlative studies

Melphalan

Intervention Type DRUG

Given IV

Peripheral Blood Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo autologous PBSC transplant

Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8

Intervention Type RADIATION

Given IV

Interventions

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Autologous Hematopoietic Stem Cell Transplantation

Undergo autologous PBSC transplant

Intervention Type PROCEDURE

Carmustine

Given IV

Intervention Type DRUG

Cytarabine

Given IV

Intervention Type DRUG

Etoposide

Given IV

Intervention Type DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Melphalan

Given IV

Intervention Type DRUG

Peripheral Blood Stem Cell Transplantation

Undergo autologous PBSC transplant

Intervention Type PROCEDURE

Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8

Given IV

Intervention Type RADIATION

Other Intervention Names

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autologous stem cell transplantation 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 .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 Demethyl Epipodophyllotoxin Ethylidine Glucoside EPEG Lastet Toposar Vepesid VP 16-213 VP-16 VP-16-213 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 PBPC transplantation PBSCT Peripheral Blood Progenitor Cell Transplantation Peripheral Stem Cell Support Peripheral Stem Cell Transplant Peripheral Stem Cell Transplantation 90Y Anti-CD45 MoAb BC8

Eligibility Criteria

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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

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No