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

NCT02483000 | Terminated Phase 1 Results FDA Drug

• 4 other identifiers: 9189NCI-2015-00299P01CA044991P30CA015704
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD) of Yttrium Y 90 DOTA-biotin Defined as the Dose That is Associated With a True Dose Limiting Toxicity (DLT) Rate of 25%, Where a DLT is Defined as a Therapy-related Grade III or IV Bearman (Transplant) Toxicity

  Following the completed observation of the final patient, a two-parameter logistic model will be fit to the data, thereby generating a dose-toxicity curve based on the observed DLT rate at the various dose levels visited. Based on this fitted model, the MTD is estimated to be the dose that is associated with a DLT rate of 25%.

  Up to 30 days after transplant

Secondary Outcomes (5)

• Dosimetry of Yttrium Y 90 DOTA-biotin

  Up to 7 days after infusion

• Incidence of Toxicity, Defined According to National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0

  Up to 30 days after transplant

• Overall Response Rate

  Up to 4 years

• Overall Survival

  Up to 4 years

• Progression Free Survival (PFS)

  1 year from autologous stem cell transplant

Study Arms (1)

Treatment (PRIT)

EXPERIMENTAL

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.

Biological: Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein; Procedure: Autologous Hematopoietic Stem Cell Transplantation; Drug: Carmustine; Drug: Clearing Agent; Drug: Cytarabine; Drug: Etoposide; Radiation: Indium In 111-DOTA-Biotin; Other: Laboratory Biomarker Analysis; Drug: Melphalan; Procedure: Peripheral Blood Stem Cell Transplantation; Other: Pharmacological Study; Radiation: Yttrium Y 90-DOTA-Biotin

Interventions

Anti-CD20 B9E9 scFv-Streptavidin Fusion Protein BIOLOGICAL

Given IV

Also known as: 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

Treatment (PRIT)

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autologous PBSCT

Also known as: Autologous Stem Cell Transplantation

Treatment (PRIT)

Carmustine DRUG

Given IV

Also known as: 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

Treatment (PRIT)

Clearing Agent DRUG

Given IV

Treatment (PRIT)

Cytarabine DRUG

Given IV

Also known as: .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

Treatment (PRIT)

Etoposide DRUG

Given IV

Also known as: Demethyl Epipodophyllotoxin Ethylidine Glucoside, EPEG, Lastet, Toposar, Vepesid, VP 16-213, VP-16, VP-16-213

Treatment (PRIT)

Indium In 111-DOTA-Biotin RADIATION

Given IV

Also known as: In 111-DOTA-Biotin

Treatment (PRIT)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (PRIT)

Melphalan DRUG

Given IV

Also known as: 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

Treatment (PRIT)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo autologous PBSCT

Also known as: PBPC transplantation, PBSCT, Peripheral Blood Progenitor Cell Transplantation, Peripheral Stem Cell Support, Peripheral Stem Cell Transplant, Peripheral Stem Cell Transplantation

Treatment (PRIT)

Pharmacological Study OTHER

Correlative studies

Treatment (PRIT)

Yttrium Y 90-DOTA-Biotin RADIATION

Given IV

Also known as: 90Y-DOTA-Biotin, yttrium Y 90 DOTA-biotin

Treatment (PRIT)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Conditions

Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Mantle-Cell; Lymphoma, B-Cell

Interventions

Carmustine; carmustine, poliferprosan 20 drug combination; Cytarabine; Etoposide; Indium; Melphalan; Peripheral Blood Stem Cell Transplantation; DOTA-biotin

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Nitrosourea Compounds; Urea; Amides; Organic Chemicals; Nitroso Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates; Metals, Heavy; Elements; Inorganic Chemicals; Metals; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Hematopoietic Stem Cell Transplantation; Stem Cell Transplantation; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative

Results Point of Contact

• Title: Dr. Ajay Gopal
• Organization: Fred Hutchinson Cancer Research Center

agopal@uw.edu

206-606-2037

Study Officials

• Ajay Gopal

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2015
• First Posted: June 26, 2015
• Study Start: February 1, 2017
• Primary Completion: November 17, 2019
• Study Completion: September 2, 2020
• Last Updated: November 23, 2020
• Results First Posted: November 23, 2020

Record last verified: 2020-09

Locations

US (1)