Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00022971
Status:
TERMINATED
Last Update Posted:
2019-12-16
First Post:
2001-08-17
Brief Title:
Combination Antibody Therapy for Relapsed Lymphoma and Chronic Lymphocytic Leukemia
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Combination Antibody Therapy With Apolizumab 1D10 and Rituximab CD20 in Relapsed Lymphoma and CLL
Status:
TERMINATED
Status Verified Date:
2017-03-17
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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
Detailed Description:
While recurrent non-Hodgkins 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 mgkg has been given in each of 4 weekly doses Preclinical in vitro data from Dr George Weiners 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 01-C-0235 | None | None | None |