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

NCT01921387 | Completed Phase 1 Results

• 4 other identifiers: 2728.00NCI-2013-01378P01CA044991P30CA015704
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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, 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.

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

Outcome Measures

Primary Outcomes (2)

• Maximum-tolerated Dose (MTD) of Yttrium-90-BC8-DOTA

  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.

  Within 30 days post-transplant

• Progression-free Survival Following Autologous Stem Cell Transplant (ASCT)

  Estimate the 1 year progression-free survival (PFS) rate after ASCT

  1 year

Secondary Outcomes (2)

• 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

• 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

Study Arms (1)

Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)

EXPERIMENTAL

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.

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

Interventions

Autologous Hematopoietic Stem Cell Transplantation PROCEDURE

Undergo autologous PBSC transplant

Also known as: autologous stem cell transplantation

Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)

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 (90Y-BC8-DOTA, chemotherapy, PBSC)

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 (90Y-BC8-DOTA, chemotherapy, PBSC)

Etoposide DRUG

Given IV

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

Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)

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 (90Y-BC8-DOTA, chemotherapy, PBSC)

Peripheral Blood Stem Cell Transplantation PROCEDURE

Undergo autologous PBSC transplant

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

Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)

Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 RADIATION

Given IV

Also known as: 90Y Anti-CD45 MoAb BC8

Treatment (90Y-BC8-DOTA, chemotherapy, PBSC)

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 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

You may not qualify if:

• 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

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

Lymphoma, B-Cell; Hodgkin Disease; Lymphoma, Mantle-Cell; Lymphoma, T-Cell

Interventions

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

Condition Hierarchy (Ancestors)

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; 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: Ajay Kumar Gopal, MD, Director of Clinical Research
• Organization: Seattle Cancer Care Alliance

agopal@uw.edu.org

(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: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 9, 2013
• First Posted: August 13, 2013
• Study Start: October 9, 2013
• Primary Completion: July 26, 2017
• Study Completion: July 26, 2020
• Last Updated: August 4, 2020
• Results First Posted: September 4, 2018

Record last verified: 2020-07

Locations

US (1)