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

NCT00006695 | Completed Phase 2

• 2 other identifiers: 0051-00-FBCOULTER-IND-3323
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Lymphoma

Keywords

recurrent adult diffuse mixed cell lymphoma; recurrent adult diffuse large cell lymphoma; recurrent adult immunoblastic large cell lymphoma

Outcome Measures

Primary Outcomes (1)

• Event free survival rate

  Participant survival without adverse events or progression

  100 days post transplant and at yearly intervals

Secondary Outcomes (2)

• Time to treatment failure

  time of registration to time of treatment discontinuation or withdrawal for progression

• Overall survival

  Time from registration to last participant death

Study Arms (1)

Arm I

EXPERIMENTAL

Iodine-131 Anti-B1 Antibody/BEAM/autologous hematopoietic stem cell transplantation (AHSCT)

Drug: carmustine; Drug: cytarabine; Drug: etoposide; Drug: melphalan; Procedure: peripheral blood stem cell transplantation; Radiation: tositumomab and iodine I 131 tositumomab

Interventions

carmustine DRUG

300 mg/m2 IV on Day -6

Also known as: BCNU

Arm I

cytarabine DRUG

100 mg/m2 BID on Days -5 through -2

Also known as: cytosine arabinoside

Arm I

etoposide DRUG

100 mg/m2 BID on Days -5 through -2

Also known as: Etopophos, Toposar

Arm I

melphalan DRUG

140 mg/m2 IV on Day -1

Also known as: Evomela

Arm I

peripheral blood stem cell transplantation PROCEDURE

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.

Also known as: Autologous Hematopoietic Stem Cell Transplantation

Arm I

tositumomab and iodine I 131 tositumomab RADIATION

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

Also known as: Iodine-131 Anti-B1 Antibody

Arm I

Eligibility Criteria

• Age: 19 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

UNMC Eppley Cancer Center at University of Nebraska Medical Center

Omaha, Nebraska, 68198-6805, United States

Location

MeSH Terms

Conditions

Lymphoma; Lymphoma, Non-Hodgkin; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Immunoblastic

Interventions

Carmustine; Cytarabine; Etoposide; etoposide phosphate; Melphalan; Peripheral Blood Stem Cell Transplantation; tositumomab I-131

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell

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

Study Officials

• Julie M. Vose, MD

  University of Nebraska

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 6, 2000
• First Posted: January 27, 2003
• Study Start: April 1, 2000
• Primary Completion: September 1, 2005
• Study Completion: December 16, 2014
• Last Updated: September 1, 2023

Record last verified: 2023-08

Locations

US (1)