Radiolabeled Monoclonal Antibody in Treating Patients With Previously Treated Large Cell Lymphoma

Phase I Safety Study Of 131I-Lym-1 For The Treatment Of Previously Treated Diffuse Large B-Cell Lymphoma

RATIONALE: Radiolabeled monoclonal antibodies can locate tumor cells and deliver tumor-killing substances such as radioactive iodine to them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibodies in treating patients who have large cell lymphoma that has been previously treated.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Radiation: iodine I 131 monoclonal antibody Lym-1

Detailed Description

OBJECTIVES:

• Determine the maximum tolerated dose of iodine I 131 monoclonal antibody Lym-1 in patients with previously treated diffuse large cell lymphoma.
• Determine the safety of this drug in these patients.
• Determine the response of patients to this drug.

OUTLINE: This is a dose-escalation, multicenter study.

Patients receive unlabeled monoclonal antibody Lym-1 IV over 40 minutes followed 15-30 minutes later by iodine I 131 monoclonal antibody Lym-1 IV over 2 minutes.

Cohorts of 3-6 patients receive escalating doses of iodine I 131 monoclonal antibody Lym-1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.

Patients are followed weekly for 8 weeks and then every 3 months for 1 year.

PROJECTED ACCRUAL: A total of 8-36 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 2
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106-5065
      • Ireland Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Histologic diagnosis of B-cell diffuse large cell lymphoma (REAL classification system) confirmed by an independent central pathology reviewer.
• The tumor's B-cell phenotype will be confirmed by positive L-26 (CD20).
• Previous treatment with 2 common combination chemotherapy regimens. Patients previously treated with unlabeled monoclonal antibody therapy are eligible.
• Men or women at least 18 years of age.
• Karnofsky Performance Score (KPS) estimated to be > 60 at the time of the scheduled therapeutic dose of 131I-Lym-1.
• Life expectancy estimated to be at least 3 months from the time of the therapeutic dose of 131I Lym-1.
• Measurable disease demonstrable by physical examination or computerized tomography (CT).
• CT scan evidence of at least one indicator lesion with at least one diameter that measures > 2 cm. (The CT scan should be done within 2 weeks of the imaging study.)

Exclusion Criteria

• Inability or unwillingness to comply with the following:
• Bone marrow biopsy
• Return for follow-up visits
• Remaining motionless for extended periods of time for imaging procedures
• Serial blood/urine sampling (for dosimetry patients only)
• Pregnancy (Women of childbearing potential must be practicing an effective method of contraception.)
• Presence of a second malignancy except for basal cell skin carcinoma or carcinoma in-situ of the cervix
• Presence of active lymphomatous meningitis or other CNS involvement with lymphoma.
• HIV positive patients.
• Prior total body irradiation, or a course of prior radiation > 3,000 cGy delivered to > 20% of the central marrow or the lumbar vertebrae within 6 months of screening.
• Serum creatinine or total bilirubin > 2 x the upper limit of normal.
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) or alkaline phosphatase > 3 x the upper limit of normal.
• Significant marrow lymphoma (defined as lymphoma cells constituting greater than 20% of the hematopoietic marrow elements from an iliac crest biopsy). A prior bone marrow biopsy is acceptable if it meets the following criteria:
• If there is prior bone marrow involvement, the biopsy must be performed within 45 days of screening.
• If there is no prior bone marrow involvement, the biopsy must be performed within 90 days of screening
• WBC count < 3,500/mm3, granulocyte count < 1,500/mm3, or platelet count < 125,000/mm3.
• Positive human anti-mouse antibodies (HAMA) serum values, defined as > 74 ng/mL at screening.
• Patients who have not recovered from toxicities of most recent anti-lymphoma therapy.
• Treatment with:
• Colony stimulating factor G-CSF or GM-CSF within 120 hours of screening laboratory assessment.
• Erythropoietin (EPO) within a month of screening laboratory assessment
• Whole blood or platelet transfusion within 120 hours of screening laboratory assessment
• History or electrocardiographic (ECG) evidence of Q-wave myocardial infarction within 6 months of screening or congestive heart failure (CHF; NYHA Stage III or IV).
• Known hypersensitivity to iodine or iodine-containing organic substances.
• Patients who require therapy with anticoagulants or antiplatelet drugs which cannot be discontinued during the study.
• Patients who are known to have antiplatelet antibodies.

Study Plan

How is the study designed?

Design Details

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

Collaborators and Investigators

• Sponsor: Case Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Study Chair: Omer N. Koc, MD, Case Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: March 1, 2001
• Primary Completion (Actual): October 1, 2001
• Study Completion (Actual): October 1, 2001

Study Registration Dates

• First Submitted: January 4, 2002
• First Submitted That Met QC Criteria: June 27, 2003
• First Posted (Estimate): June 30, 2003

Study Record Updates

• Last Update Posted (Estimate): January 9, 2014
• Last Update Submitted That Met QC Criteria: January 8, 2014
• Last Verified: January 1, 2014

More Information

Terms related to this study

• Keywords: recurrent adult diffuse large cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Monoclonal
• Other Study ID Numbers: BRLX1400; CWRU-BRLX-1400; BRLX-303680; CWRU-090036; NCI-G01-2038