Diffuse Large B-Cell LymphomaPhase 1NCT00022971
Combination Antibody Therapy for Relapsed Lymphoma and Chronic Lymphocytic Leukemia
A Phase 1 study testing Apolizumab and Rituximab in people with Diffuse Large B-Cell Lymphoma and Follicular Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, Chronic Lymphocytic Leukemia
- What is being tested?
- Apolizumab and Rituximab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- 15 Aug 2001to 17 Mar 2017
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Combination Antibody Therapy With Apolizumab (1D10) and Rituximab (CD20) in Relapsed Lymphoma and CLL
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).
Read more
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.
...
Read the 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.
- Conditions
- Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, Chronic Lymphocytic Leukemia, Mantle Cell Lymphoma, Small Lymphocytic Lymphoma
- Being tested
- Apolizumab, Rituximab
- Keywords
- Monoclonal Antibody, Lymphoma, Rituximab, Hu1D10, Non-Hodgkin's Lymphoma, NHL, Chronic Lymphocytic Leukemia, CLL, Leukemia
- Medical subject headings
- Lymphoma, Large B-Cell, Diffuse, Lymphoma, Follicular, Leukemia, Lymphocytic, Chronic, B-Cell, Lymphoma, Mantle-Cell, Lymphoma, Lymphoma, Non-Hodgkin, Leukemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ApolizumabBiological
Apolizumab IV on Day 1. Administer weekly for 4 weeks
RituximabBiological
Rituximab IV 24-36 hours after Apolizumab ends. Administer weekly for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Apolizumab followed by rituixmab every 4 weeks Receives: Biological: Apolizumab; Biological: Rituximab |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD
Measured: After one cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2001 (estimated)
- Study start15 Aug 2001
- Primary completion22 Jan 2010
- Study completion17 Mar 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diffuse Large B-Cell LymphomaStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Wyndham H Wilson, M.D., Principal investigator, National Cancer Institute (NCI)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00022971
- Sponsor's protocol ID
- 010235
- Other IDs
- 01-C-0235
- Status last verified
- 17 Mar 2017
- First submitted
- 17 Aug 2001
- Last updated
- 16 Dec 2019
- Results posted
- No
Publications
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.
PubMed 9473230McLaughlin P. Inroads in the therapy of indolent lymphomas: exploiting biological insights. Cancer Invest. 1999;17(1):73-86. No abstract available.
PubMed 10999051Weiner LM. Monoclonal antibody therapy of cancer. Semin Oncol. 1999 Oct;26(5 Suppl 14):43-51.
PubMed 10561017
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Combination Antibody Therapy With Apolizumab (1D10) and Rituximab (CD20) in Relapsed Lymphoma and CLL
- ClinicalTrials.gov ID
- NCT00022971
- Acronym / sponsor ID
- 010235
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 35 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- 15 Aug 2001
- Primary completion
- 22 Jan 2010 (actual)
- Study completion
- 17 Mar 2017 (actual)
- First posted
- 20 Aug 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
...
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Biological: Apolizumab, Biological: RituximabApolizumab followed by rituixmab every 4 weeks |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ApolizumabApolizumab IV on Day 1. Administer weekly for 4 weeks | Biological | 1 |
| RituximabRituximab IV 24-36 hours after Apolizumab ends. Administer weekly for 4 weeks | Biological | 1 |
Primary outcome
MTD
Time frame: After one cycle
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2019.
- Background: PubMed 9473230Shan 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.
- Background: PubMed 10999051McLaughlin P. Inroads in the therapy of indolent lymphomas: exploiting biological insights. Cancer Invest. 1999;17(1):73-86. No abstract available.
- Background: PubMed 10561017Weiner LM. Monoclonal antibody therapy of cancer. Semin Oncol. 1999 Oct;26(5 Suppl 14):43-51.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Wyndham H Wilson, M.D. principal investigator
National Cancer Institute (NCI)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Apolizumab and Rituximab in people with Diffuse Large B-Cell Lymphoma and Follicular Lymphoma, run by National Cancer Institute (NCI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 16 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MTD (time frame: After one cycle). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00022971, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Dec 2019.