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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2016 by Fred Hutchinson Cancer Research Center
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier:
NCT01921387
First received: August 9, 2013
Last updated: July 28, 2016
Last verified: July 2016
  Purpose
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.

Condition Intervention Phase
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
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
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study Evaluating Escalating Doses of 90Y-BC8-DOTA (Anti-CD45) Antibody Followed by BEAM Chemotherapy and Autologous Stem Cell Transplantation for High-Risk Lymphoid Malignancies

Resource links provided by NLM:


Further study details as provided by Fred Hutchinson Cancer Research Center:

Primary Outcome Measures:
  • MTD of yttrium Y 90 anti-CD45 monoclonal antibody BC8, defined as the dose that is associated with a true dose-limiting toxicity (DLT) rate of 25% [ Time Frame: Within 30 days post-transplant ] [ Designated as safety issue: Yes ]
    DLT is defined as a therapy-related grade III or IV Bearman (transplant) toxicity.

  • Progression-free survival following ASCT [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
  • The lowest antibody (yttrium Y 90 anti-CD45 monoclonal antibody BC8) dose (mg/kg) that is consistent with a favorable biodistribution rate >= 80% in lymphoma patients [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    A favorable biodistribution in a given patient will be defined by the target tissue receiving higher radiation dose per unit-administered activity (cGy/mCi) relative to all critical normal organs (lung, liver, kidney, etc.).


Estimated Enrollment: 44
Study Start Date: October 2013
Estimated Primary Completion Date: September 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Procedure: Autologous Hematopoietic Stem Cell Transplantation
Undergo autologous PBSC transplant
Other Name: Autologous Stem Cell Transplantation
Drug: Carmustine
Given IV
Other Names:
  • 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
Drug: Cytarabine
Given IV
Other Names:
  • .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
Drug: Etoposide
Given IV
Other Names:
  • Demethyl Epipodophyllotoxin Ethylidine Glucoside
  • EPEG
  • Lastet
  • Toposar
  • Vepesid
  • VP 16-213
  • VP-16
  • VP-16-213
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Melphalan
Given IV
Other Names:
  • 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
Procedure: Peripheral Blood Stem Cell Transplantation
Undergo autologous PBSC transplant
Other Names:
  • PBPC transplantation
  • Peripheral Blood Progenitor Cell Transplantation
  • Peripheral Stem Cell Support
  • Peripheral Stem Cell Transplantation
Radiation: Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8
Given IV
Other Name: 90Y Anti-CD45 MoAb BC8

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01921387

Locations
United States, Washington
Fred Hutch/University of Washington Cancer Consortium Recruiting
Seattle, Washington, United States, 98109
Contact: Ajay K. Gopal    206-288-2037    agopal@u.washington.edu   
Principal Investigator: Ajay K. Gopal         
Sponsors and Collaborators
Fred Hutchinson Cancer Research Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Ajay Gopal Fred Hutch/University of Washington Cancer Consortium
  More Information

Responsible Party: Fred Hutchinson Cancer Research Center
ClinicalTrials.gov Identifier: NCT01921387     History of Changes
Other Study ID Numbers: 2728.00  NCI-2013-01378  2728.00  P01CA044991  P30CA015704 
Study First Received: August 9, 2013
Last Updated: July 28, 2016
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Hodgkin Disease
Lymphoma, Mantle-Cell
Lymphoma, T-Cell
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antibodies
Immunoglobulins
Antibodies, Monoclonal
Cytarabine
Melphalan
Etoposide
Podophyllotoxin
Etoposide phosphate
Carmustine
Mechlorethamine
Nitrogen Mustard Compounds
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 28, 2016