Combination Antibody Therapy for Relapsed Lymphoma and Chronic Lymphocytic Leukemia
This study will evaluate the safety and effectiveness of a combination of two antibodies, apolizumab and rituximab (Rituxan(Registered Trademark)), 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(Registered Trademark)), and acetominophen (Tylenol(Registered Trademark)) 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.
Chronic Lymphocytic Leukemia
Drug: Remitogen (Apolizumab)
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Combination Antibody Therapy With Apolizumab (1D10) and Rituximab (CD20) in Relapsed Lymphoma and CLL|
- Maximum tolerated dose (MTD) and toxicity of apolizumab. [ Designated as safety issue: Yes ]
- Antitumor activity at the MTD at the end of study treatment [ Designated as safety issue: Yes ]
- Pharmacokinetics [ Designated as safety issue: No ]
- Effects of treatment in patients with chronic lymphocytic leukemia (CLL) as measured by microarray profiling pre-treatment and at the end of study treatment [ Designated as safety issue: No ]
- Effects of treatment in patients with CLL on kinetics of apoptosis as measured by fluorescent-activated cell sorting (FACS) analysis of Annnexin 5 pre-treatment and at the end of study treatment [ Designated as safety issue: No ]
- Effects of treatment on T-cell and B-cell levels pre-treatment, during treatment, and at the end of study treatment [ Designated as safety issue: No ]
|Study Start Date:||August 2001|
|Study Completion Date:||January 2010|
|Primary Completion Date:||January 2010 (Final data collection date for primary outcome measure)|
Drug: Remitogen (Apolizumab)
While recurrent non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL) are often responsive to therapy, they are rarely curable and disease control is the primary therapeutic goal. Rituximab, a chimeric anti-CD20 monoclonal antibody, has shown single agent activity in these diseases and is currently approved for the therapy of recurrent indolent lymphoma. However, rituximab induces objective remission in at most 60% of cases with inevitable relapse. The 1D10 antigen, a subclass of the HLA-DR molecule, is expressed in a majority of cases of B-cell malignancy. Apolizumab is a humanized monoclonal antibody that targets this antigen. In a phase I dose escalation trial this antibody has shown clinical activity against B-cell NHL that express the 1D10 antigen. Acute infusional toxicity has been tolerable, and a maximum of 5 mg/kg has been given in each of 4 weekly doses. Preclinical in vitro data from Dr. George Weiner's laboratory suggests at least additive anti-tumor efficacy when cells are exposed to both antibodies simultaneously. This trial will pilot the use of combination therapy with rituximab and apolizumab in patients with tumors that express both antigens. Feasibility and tolerability of the regimen will be determined. Experimental endpoints will include pharmacokinetics of apolizumab, assessment of apoptosis in circulating CLL cells by FACS analysis with Annexin 5, assessment of T-and B-cell dynamics, and effects of rituximab and apolizumab on CLL mRNA as measured by cDNA microarray. Following the first 21 patients on trial, the administration sequence of rituximab and apolizumab was changed from rituximab first to apolizumab first to potentially reduce sensitization of apolizumab toxicity by rituximab.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Wyndham H Wilson, M.D.||National Cancer Institute (NCI)|