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Combination Antibody Therapy for Relapsed Lymphoma and Chronic Lymphocytic Leukemia

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ClinicalTrials.gov Identifier: NCT00022971
Recruitment Status : Terminated
First Posted : August 20, 2001
Last Update Posted : December 16, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )

Study Description
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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.

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Condition or disease Intervention/treatment Phase
Diffuse Large B-Cell Lymphoma Follicular Lymphoma Chronic Lymphocytic Leukemia Mantle Cell Lymphoma Small Lymphocytic Lymphoma Biological: Apolizumab Biological: Rituximab Phase 1

Detailed Description:
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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 35 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Combination Antibody Therapy With Apolizumab (1D10) and Rituximab (CD20) in Relapsed Lymphoma and CLL
Study Start Date : August 15, 2001
Actual Primary Completion Date : January 22, 2010
Actual Study Completion Date : March 17, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Leukemia Lymphoma
Drug Information available for: Rituximab

Arms and Interventions
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Arm Intervention/treatment
Experimental: 1
Apolizumab followed by rituixmab every 4 weeks
 Biological: Apolizumab
Apolizumab IV on Day 1. Administer weekly for 4 weeks

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


Outcome Measures
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Primary Outcome Measures :
  1. MTD [ Time Frame: After one cycle ]

Eligibility Criteria
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Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 100 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

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.

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00022971


Locations
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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Wyndham H Wilson, M.D. National Cancer Institute (NCI)
More Information
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Publications:

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Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00022971    
Obsolete Identifiers: NCT00029367
Other Study ID Numbers: 010235
01-C-0235
First Posted: August 20, 2001    Key Record Dates
Last Update Posted: December 16, 2019
Last Verified: March 17, 2017
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) ):
Monoclonal Antibody
Lymphoma
Rituximab
Hu1D10
Non-Hodgkin's Lymphoma
 NHL
Chronic Lymphocytic Leukemia
CLL
Leukemia
Additional relevant MeSH terms:
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Lymphoma
Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Lymphoma, Mantle-Cell
Lymphoma, Large B-Cell, Diffuse
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
 Immune System Diseases
Lymphoma, Non-Hodgkin
Leukemia, B-Cell
Lymphoma, B-Cell
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents