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

NCT ID: NCT02483000

Last Updated: 2020-11-23

Study Results

Results available

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Basic Information

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Recruitment Status

TERMINATED

Clinical Phase

PHASE1

Total Enrollment

3 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-02-01

Study Completion Date

2020-09-02

Brief Summary

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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.

Detailed Description

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PRIMARY OBJECTIVES:

I. 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:

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

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

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

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

TERTIARY OBJECTIVES:

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

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

III. 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.

Conditions

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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

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 (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.

Group Type EXPERIMENTAL

Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein

Intervention Type BIOLOGICAL

Given IV

Autologous Hematopoietic Stem Cell Transplantation

Intervention Type PROCEDURE

Undergo autologous PBSCT

Carmustine

Intervention Type DRUG

Given IV

Clearing Agent

Intervention Type DRUG

Given IV

Cytarabine

Intervention Type DRUG

Given IV

Etoposide

Intervention Type DRUG

Given IV

Indium In 111-DOTA-Biotin

Intervention Type RADIATION

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 PBSCT

Pharmacological Study

Intervention Type OTHER

Correlative studies

Yttrium Y 90-DOTA-Biotin

Intervention Type RADIATION

Given IV

Interventions

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Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein

Given IV

Intervention Type BIOLOGICAL

Autologous Hematopoietic Stem Cell Transplantation

Undergo autologous PBSCT

Intervention Type PROCEDURE

Carmustine

Given IV

Intervention Type DRUG

Clearing Agent

Given IV

Intervention Type DRUG

Cytarabine

Given IV

Intervention Type DRUG

Etoposide

Given IV

Intervention Type DRUG

Indium In 111-DOTA-Biotin

Given IV

Intervention Type RADIATION

Laboratory Biomarker Analysis

Correlative studies

Intervention Type OTHER

Melphalan

Given IV

Intervention Type DRUG

Peripheral Blood Stem Cell Transplantation

Undergo autologous PBSCT

Intervention Type PROCEDURE

Pharmacological Study

Correlative studies

Intervention Type OTHER

Yttrium Y 90-DOTA-Biotin

Given IV

Intervention Type RADIATION

Other Intervention Names

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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 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 In 111-DOTA-Biotin 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-DOTA-Biotin yttrium Y 90 DOTA-biotin

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role collaborator

Fred Hutchinson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Ajay Gopal

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

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Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

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NCI-2015-00299

Identifier Type: REGISTRY

Identifier Source: secondary_id

9189

Identifier Type: OTHER

Identifier Source: secondary_id

P01CA044991

Identifier Type: NIH

Identifier Source: secondary_id

View Link

P30CA015704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

9189

Identifier Type: -

Identifier Source: org_study_id