Monoclonal Antibody Therapy, Combination Chemotherapy, and Peripheral Stem Cell Transplant in Non-Hodgkin's Lymphoma

BEAM Plus Iodine-131 Anti-B1 Antibody and Autologous Hematopoietic Stem Cell Transplantation for Treatment of Recurrent Diffuse Large B-Cell Non-Hodgkin's Lymphoma

RATIONALE: Monoclonal antibodies can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with peripheral stem cell transplant may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells.

PURPOSE: This phase II trial is studying how well monoclonal antibody therapy, chemotherapy, and peripheral stem cell transplant work in treating patients with relapsed or refractory non-Hodgkin's lymphoma.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Drug: carmustine; Drug: cytarabine; Drug: etoposide; Drug: melphalan; Procedure: peripheral blood stem cell transplantation; Radiation: tositumomab and iodine I 131 tositumomab

Detailed Description

OBJECTIVES:

• Compare the response rates and time to treatment failure in patients with relapsed or refractory non-Hodgkin's lymphoma treated with iodine I 131 monoclonal antibody anti-B1, followed by high-dose carmustine, etoposide, cytarabine, and melphalan (BEAM), and autologous peripheral blood stem cell transplantation (APBSCT) vs historical control patients treated with high-dose BEAM or carmustine, etoposide, cytarabine, and cyclophosphamide and APBSCT.
• Determine the safety of this regimen in these patients.

OUTLINE: Autologous peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells or granulocyte macrophage colony-forming units. On day -19, patients receive unlabeled monoclonal antibody anti-B1 (MOAB anti-B1) IV followed by a dosimetric dose of iodine I 131 MOAB anti-B1 IV over 20 minutes. On day -12, patients receive unlabeled MOAB anti-B1 IV followed by a therapeutic dose of iodine I 131 MOAB anti-B1 IV over 20 minutes. Patients then receive high-dose chemotherapy comprising carmustine IV on day -6, etoposide IV and cytarabine IV twice daily on days -5 to -2, and melphalan IV on day -1. Patients undergo autologous PBSC transplantation on day 0.

Patients are followed at days 30 and 100, at 6 months, and then annually thereafter.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study over 5 years.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Nebraska
    • Omaha, Nebraska, United States, 68198-6805
      • UNMC Eppley Cancer Center at University of Nebraska Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 15 years to 66 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of non-Hodgkin's lymphoma (NHL) of one of the following types:

  • Diffuse large B-cell
  • Composite (at least 50% of tumor showing diffuse histology)
  • Diffuse mixed cell
  • Immunoblastic
• Relapsed or refractory disease sensitive to initial or subsequent conventional therapy (at least a partial response)
• Eligible for high-dose carmustine, etoposide, cytarabine, and melphalan protocol and autologous bone marrow transplantation or peripheral blood stem cell transplantation
• Evidence of CD20 antigen expression in tumor tissue
• Bidimensionally measurable disease

• Adequate peripheral blood stem cells

  • At least 15,000,000 CD34+ cells/kg or
  • At least 25,000 granulocyte macrophage colony-forming units/kg
• Age: 19 to 70
• Performance status: Karnofsky 70-100%
• Life expectancy: at least 4 months post-transplantation
• Bilirubin less than 2.0 mg/dL
• Creatinine less than 2.0 mg/dL

• Cardiac ejection fraction at least 40% for any of the following criteria:

  • Age 60 and over
  • Significant cardiac history (myocardial infarction or congestive heart failure)
  • Received greater than 350 mg/m^2 of prior doxorubicin
• DLCO at least 50% of predicted
• HIV negative
• Fertile patients must use effective contraception during and for at least 6 months after study participation
• At least 4 weeks since prior biologic therapy and recovered
• Human antimouse antibody negative
• At least 4 weeks since prior cytotoxic chemotherapy and recovered
• At least 4 weeks since prior radiotherapy and recovered
• At least 4 weeks since prior immunosuppressants and recovered

Exclusion Criteria:

• No progressive disease in a field that has been previously irradiated with more than 3,500 cGy within the past year
• No known brain or leptomeningeal metastases
• No active obstructive hydronephrosis
• No New York Heart Association class III or IV heart disease
• No evidence of severe organ dysfunction
• No other major medical illnesses
• No active infection requiring IV antibiotics
• No other malignancy within the past 5 years except adequately treated skin cancer or carcinoma in situ of the cervix
• Not pregnant/negative pregnancy test
• No prior peripheral blood stem cell transplantation following high-dose chemotherapy or chemoradiotherapy
• No other concurrent biologic therapy for NHL
• No concurrent steroids except maintenance-dose steroids for noncancerous disease
• No concurrent external beam radiotherapy for NHL
• No other concurrent participation on protocol involving non-FDA-approved drugs or biologics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Arm I; Iodine-131 Anti-B1 Antibody/BEAM/autologous hematopoietic stem cell transplantation (AHSCT)

Drug: carmustine; 300 mg/m2 IV on Day -6; Other Names: BCNU; Drug: cytarabine; 100 mg/m2 BID on Days -5 through -2; Other Names: cytosine arabinoside; Drug: etoposide; 100 mg/m2 BID on Days -5 through -2; Other Names: Etopophos, Toposar; Drug: melphalan; 140 mg/m2 IV on Day -1; Other Names: Evomela; Procedure: peripheral blood stem cell transplantation; Following the chemotherapy, on Day 0 of treatment, the previously stored hematopoietic stem cells will be administered to the patient intravenously through a central line to the patient.; Other Names: Autologous Hematopoietic Stem Cell Transplantation; Radiation: tositumomab and iodine I 131 tositumomab; Patients will receive two administrations of Iodine-131 Anti-B1 Antibody; the "dosimetric dose" and the "therapeutic dose". The dosimetric dose will consist of an infusion of unlabeled Anti-B1 Antibody (450 mg) immediately followed by an infusion of Anti-B1 Antibody (35 mg) which has been trace labeled with 5 mCi of Iodine-131 Anti-B1 Antibody. Using whole body anterior and posterior gamma camera scans and serial imaging studies over approximately one week, the clearance of the whole body dosimetric dose will be used to calculate the subsequent therapeutic dose of Iodine-131 Anti-B1 Antibody which delivers a total body dose of 75 cGy to the subject; Other Names: Iodine-131 Anti-B1 Antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Event free survival rate	Participant survival without adverse events or progression	100 days post transplant and at yearly intervals

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to treatment failure	Time from registration to time of treatment discontinuation or withdrawal for progression	time of registration to time of treatment discontinuation or withdrawal for progression
Overall survival	Time from first participant enrollment to last participant death or end of study	Time from registration to last participant death

Collaborators and Investigators

• Sponsor: University of Nebraska
• Investigators: Study Chair: Julie M. Vose, MD, University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2000
• Primary Completion (Actual): September 1, 2005
• Study Completion (Actual): December 16, 2014

Study Registration Dates

• First Submitted: December 6, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimated): January 27, 2003

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma; recurrent adult diffuse mixed cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Trace Elements; Micronutrients; Etoposide; Melphalan; Iodine; Tositumomab I-131; Cytarabine; Carmustine
• Other Study ID Numbers: 0051-00-FB; COULTER-IND-3323 (Other Grant/Funding Number: Coulter Pharmaceuticals, Inc.)