Combination Antibody Therapy for Relapsed Lymphoma and Chronic Lymphocytic Leukemia

NCT00022971 | Terminated Phase 1

• 2 other identifiers: 01023501-C-0235
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This study will evaluate the safety and effectiveness of a combination of two antibodies, apolizumab and rituximab (Rituxan ), in treating B-cell lymphomas and chronic lymphocytic leukemia. Rituximab attaches to a molecule called CD20 on B-cell lymphomas and can cause significant shrinkage of these tumors in up to half of patients. However, it does not cure the lymphoma, which usually returns. Also, it is not as effective against leukemia. Apolizumab attaches to a protein called 1D10 on B-cell cancers and has also been able to shrink tumors in some patients. There is little experience apolizumab in patients with leukemia. This study will test whether the two antibodies together are more effective against these tumors than either one alone. Patients 18 years and older with B-cell lymphoma or chronic lymphocytic leukemia may be eligible for this study. Patients' leukemia or lymphoma cells must have both the CD20 and 1D10 antigen receptors and must have had at least one systemic treatment for their disease. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram, x-rays and other imaging studies, and possibly a bone marrow aspirate (withdrawal of a small marrow sample through a needle inserted into the hip bone) and lumbar puncture (withdrawal of a small sample of cerebrospinal fluid-fluid that bathes the brain and spinal cord-through a needle placed between the bones in the lower back). Participants receive infusions of rituximab and apolizumab once a week for 4 weeks. The first patients in the study receive lower doses of apolizumab with standard doses of rituximab. If the apolizumab is well tolerated, subsequent patients are given higher doses. Patients are also given dexamethasone or another similar steroid, diphenhydramine (Benadryl ), and acetominophen (Tylenol ) to reduce reactions to the antibodies. After 4 weeks of treatment, patients are followed frequently to examine the response to treatment and evaluate drug side effects. Patients whose tumors do not grow during the 4 weeks of therapy may be offered another course of treatment at a later time. Participants are followed periodically after treatment ends until their disease worsens or the study ends. ...

Conditions

Diffuse Large B-Cell Lymphoma; Follicular Lymphoma; Chronic Lymphocytic Leukemia; Mantle Cell Lymphoma; Small Lymphocytic Lymphoma

Keywords

Monoclonal Antibody; Lymphoma; Rituximab; Hu1D10; Non-Hodgkin's Lymphoma; NHL; Chronic Lymphocytic Leukemia; CLL; Leukemia

Outcome Measures

Primary Outcomes (1)

• MTD

  After one cycle

Study Arms (1)

1

EXPERIMENTAL

Apolizumab followed by rituixmab every 4 weeks

Biological: Apolizumab; Biological: Rituximab

Interventions

Apolizumab BIOLOGICAL

Apolizumab IV on Day 1. Administer weekly for 4 weeks

1

Rituximab BIOLOGICAL

Rituximab IV 24-36 hours after Apolizumab ends. Administer weekly for 4 weeks

1

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of B-cell lymphoma, Waldenstrom's CLL with surface expression of both CD20 and 1D10 antigen by immunohistochemistry (IHC) or fluorescence of activated cell sorting (FACS) with anti-CD20 and 1D10 antibody. Positive 1D10 expression in a FACS assay is defined as more than 2 times the mean fluorescence intensity (MFI) of the control antibody by FACS or greater than 20% of cells 1D10+ by IHC.
• Confirmation of diagnosis in Laboratory of Pathology, NCI or OSU.
• Prior therapy with at least one systemic treatment, and not a candidate for potentially curative (i.e., transplant) treatment at the time of study entry. Prior treatment with rituximab greater than or equal to 1 month ago is permitted.
• Age greater than 18 years.
• ECOG performance status less than or equal to 2.
• Major organ function: ANC greater than or equal to 500/microliter, Platelet greater than or equal 25,000/microliter, Creatinine less than or equal to 1.5 mg/dl or creatinine clearance greater than 60 cc/min; SGPT less than 5 x upper limit of normal; bilirubin less than 2 mg/dl (total) except less than 5 mg/dl in patients with Gilbert's syndrome as defined by greater than 80% unconjugated; unless impairment due to organ involvement by lymphoma.
• Provides informed consent.

You may not qualify if:

• Pregnancy or nursing. Both male and female patients must be willing to use adequate contraception.
• Prior apolizumab treatment.
• SActive cardiac disease, cerebrovascular disease or peripheral arterial vascular disease.
• Active CNS lymphoma.
• Systemic cytotoxic chemotherapy within 3 weeks of enrollment or systemic steroids (except stable doses less than 10 mg/day) within 1 week of enrollment.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Shan D, Ledbetter JA, Press OW. Apoptosis of malignant human B cells by ligation of CD20 with monoclonal antibodies. Blood. 1998 Mar 1;91(5):1644-52.

  PMID: 9473230 BACKGROUND

• McLaughlin P. Inroads in the therapy of indolent lymphomas: exploiting biological insights. Cancer Invest. 1999;17(1):73-86. No abstract available.

  PMID: 10999051 BACKGROUND

• Weiner LM. Monoclonal antibody therapy of cancer. Semin Oncol. 1999 Oct;26(5 Suppl 14):43-51.

  PMID: 10561017 BACKGROUND

MeSH Terms

Conditions

Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphoma, Mantle-Cell; Lymphoma; Lymphoma, Non-Hodgkin; Leukemia

Interventions

apolizumab; Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, B-Cell; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Wyndham H Wilson, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 17, 2001
• First Posted: August 20, 2001
• Study Start: August 15, 2001
• Primary Completion: January 22, 2010
• Study Completion: March 17, 2017
• Last Updated: December 16, 2019

Record last verified: 2017-03-17

Locations

US (1)