Adult Grade III Lymphomatoid GranulomatosisPhase 1/2NCT00089076
MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma
A Phase 1/2 study testing ipilimumab and laboratory biomarker analysis in people with Adult Grade III Lymphomatoid Granulomatosis and B-cell Chronic Lymphocytic Leukemia, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Biological therapies, such as MDX-010, work in different ways to stimulate the immune system and stop cancer cells from growing. This phase I/II trial is studying the side effects and best dose of MDX-010 and to see how well it works in treating patients with recurrent or refractory B-cell non-Hodgkin's lymphoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adult Grade III Lymphomatoid Granulomatosis, B-cell Chronic Lymphocytic Leukemia, Cutaneous B-cell Non-Hodgkin Lymphoma
- What is being tested?
- ipilimumab and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2004to Oct 2009
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologic proof of recurring or residual follicular B-cell non-Hodgkin's lymphoma (grade I or II), by Revised European American Lymphoma Classification (REAL) or World Health Organization (WHO) classifications which has relapsed or persisted after 3 or fewer conventional therapies, including chemotherapy or monoclonal antibody therapy; note: all patients with previously treated B-cell lymphomas of any histology with the exception of small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL) are eligible
- Tumor measurable by computed tomography (CT) scans (at least one pathologic node measuring 2.0 x 2.0 cm, or 2 nodes measuring > 1.5 x 1.5 cm after collection of tumor for immunologic analyses)
- At least one prior treatment regimen but no more than 3 prior chemotherapy regimens; patients previously treated with monoclonal antibodies or radiotherapy to a single site will be eligible; these therapies will be considered prior treatment regimens but will not be considered as prior chemotherapy; tumor vaccines will not be counted as prior therapies, as all such agents are investigational
- Absolute neutrophil count (ANC) >= 1000/uL
- Platelets (PLT) >= 75,000/uL
- Total bilirubin =< 1.5 x upper limit of normal (ULN)
Show all 13Show fewer
- Aspartate aminotransferase (AST) =< 3 x upper limit or normal (ULN)
- Creatinine =< 1.5 x ULN
- Hemoglobin >= 8 g/dL
- Ability to provide informed consent
- Willingness to return to the Mayo Clinic Rochester or the University of California, Los Angeles for follow up
- Life expectancy >= 24 weeks
- Willingness to provide all biologic specimens as required by the protocol
Who cannot join
- Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2, 3, or 4
- Any uncontrolled infection, hepatitis C virus (HCV)+ (unless HCV ribonucleic acid [RNA]-negative by polymerase chain reaction [PCR]) or hepatitis B surface antigen (HBsAg)+, or human immunodeficiency virus (HIV) positive patients or patients with known immune deficiency states
- Previous MDX-010 therapy regardless of interval since last treatment
- Prior treatment with fludarabine or 2-chlorodeoxyadenosine =< 12 months prior to registration
- Failure to fully recover from acute, reversible effects of prior chemotherapy regardless of interval since last treatment
Show all 17Show fewer
- New York Heart Association classification III or IV or a history of angina pectoris requiring active treatment
- Clinical evidence of central nervous system involvement by lymphoma
- Any of the following:
- Pregnant women
- Nursing women
- Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device [IUD], or abstinence, etc.)
- Other concurrent chemotherapy, immunotherapy, radiotherapy, or any ancillary therapy considered investigational (utilized for a non-Food and Drug Administration [FDA]-approved indication and in the context of a research investigation)
- Diagnosis of small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL)
- Any requirement for concurrent steroid therapy, including use of inhaled steroids for asthma
- History of autoimmune disease requiring systemic therapy with immunosuppressive drugs, including but not limited to rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, multiple sclerosis, or psoriasis
- Antinuclear antibody (ANA) titer or rheumatoid factor titer > 3x institutional ULN
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I/II Study of Anti-CTLA-4 Monoclonal Antibody (MDX-010) in B-cell Non-Hodgkin's Lymphoma
Biological therapies, such as MDX-010, work in different ways to stimulate the immune system and stop cancer cells from growing. This phase I/II trial is studying the side effects and best dose of MDX-010 and to see how well it works in treating patients with recurrent or refractory B-cell non-Hodgkin's lymphoma.
Read the detailed description
PRIMARY OBJECTIVES:
- To characterize the safety profile of MDX-010 (ipilimumab) monoclonal antibody and identify a tolerable immunologically active dose level in B cell lymphoma patients.
II. To evaluate the clinical response rate in B cell lymphoma patients treated with MDX-010.
SECONDARY OBJECTIVES:
- To evaluate the phenotype and function of memory T cells before and after treatment with MDX-010 by:
- Quantitation and phenotypic characterization of peripheral blood and tumor infiltrating T-cells, including cluster of differentiation (CD)4+CD25+ regulatory T cells.
- Measurement of tumor-specific T cells in peripheral blood lymphocytes.
- Measuring proliferation of memory T cells in response to recall antigens (tetanus toxoid and keyhole limpet hemocyanin [KLH]).
II. Measurement of anti-tumor antibodies in serum pre- and post-therapy. III. To evaluate the time to progression. IV. To evaluate the duration of response to treatment with MDX-010.
OUTLINE: This is a multicenter, open-label, phase I, dose-escalation study followed by a phase II study. Patients are grouped according to prior treatment with a vaccine therapy for lymphoma (yes vs no).
PHASE I: Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 6 patients from each group receive escalating doses of MDX-010 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
PHASE II: Patients receive MDX-010 as in phase I at the MTD.
Patients are followed at 1 and 4 months and then every 6 months for up to 2 years.
- Conditions
- Adult Grade III Lymphomatoid Granulomatosis, B-cell Chronic Lymphocytic Leukemia, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma
- Being tested
- ipilimumab, laboratory biomarker analysis
- Medical subject headings
- Leukemia, Lymphocytic, Chronic, B-Cell, Intraocular Lymphoma, Lymphoma, B-Cell, Marginal Zone, Burkitt Lymphoma, Lymphoma, Large B-Cell, Diffuse, Lymphoma, Non-Hodgkin, Hodgkin Disease, Lymphoma, Large-Cell, Immunoblastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ipilimumabBiological
Also called anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody, MDX-010, MDX-CTLA-4, monoclonal antibody CTLA-4
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (ipilimumab) | Experimental | PHASE I: Patients receive MDX-010 IV over 90 minutes on day 1. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 6 patients from each group receive escalating doses of MDX-010 until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
PHASE II: Patients receive MDX-010 as in phase I at the MTD. Receives: Biological: ipilimumab; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Overall Confirmed Responses(Complete Response or Partial Response)
Confirmed response is at least a 50% decrease in the sum of the products of the greatest diameters (SPD) of the six largest dominant nodes or nodal masses and no increase in the size of other nodes, liver, or spleen and splenic and hepatic nodules must regress by at least 50% in the SPD and no new sites of disease.
Measured: From registration to month 7
Secondary outcomes (7)
Time to Progression (Phase 2)
The time to progression is defined as the time from registration to the time of progression. Those who die will be considered to have had disease progression unless documented evidence clearly indicates no progression has occurred. The distribution of time to progression will be estimated using the method of Kaplan-Meier.
Measured: From registration to progression (up to 2 years)
Overall Survival (Phase 2)
The overall survival or survival time is defined as the time from registration to death due to any cause. The distribution of overall survival will be estimated using the method of Kaplan-Meier.
Measured: From registration to death (up to 2 years)
Duration of Response (Phase 2)
Duration of response will be calculated from the documentation of confirmed response until the date of progression in the subset of patients who respond.
Measured: From response to progression (up to 2 years)
Mean Change in % of CD3+CD4+ for Marker HLA-DR+
Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy
Measured: Before treatment to 1 month after therapy initiation
Mean Change in % of CD3+CD4- for Marker HLA-DR+
Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy
Measured: Before treatment to 1 month after therapy initiation
Mean Change in % of CD3+CD4+ for Marker CD45RO+
Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy
Measured: Before treatment to 1 month after therapy initiation
Mean Change in % of CD3+CD4- for the Marker CD45RO+
Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy
Measured: Before treatment to 1 month after therapy initiation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Aug 2004 (estimated)
- Study startJun 2004
- Primary completionJul 2008
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Adult Grade III Lymphomatoid GranulomatosisStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Stephen Ansell, Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00089076
- Sponsor's protocol ID
- NCI-2012-02784
- Other IDs
- NCI-2012-02784, MC0312, 6359, P30CA015083, U01CA069912
- Status last verified
- Dec 2012
- First submitted
- 4 Aug 2004
- Last updated
- 30 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
Study at a glance
From the registry record, last updated by the sponsor on 30 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Anti-CTLA-4 Monoclonal Antibody (MDX-010) in B-cell Non-Hodgkin's Lymphoma
- ClinicalTrials.gov ID
- NCT00089076
- Acronym / sponsor ID
- NCI-2012-02784
- Conditions
- Adult Grade III Lymphomatoid Granulomatosis, B-cell Chronic Lymphocytic Leukemia, Cutaneous B-cell Non-Hodgkin Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Terminated
- Enrolment
- 18 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jun 2004
- Primary completion
- Jul 2008 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 5 Aug 2004 (estimated)
- Results
- Posted 19 Oct 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Biological therapies, such as MDX-010, work in different ways to stimulate the immune system and stop cancer cells from growing. This phase I/II trial is studying the side effects and best dose of MDX-010 and to see how well it works in treating patients with recurrent or refractory B-cell non-Hodgkin's lymphoma.
Detailed description
PRIMARY OBJECTIVES:
- To characterize the safety profile of MDX-010 (ipilimumab) monoclonal antibody and identify a tolerable immunologically active dose level in B cell lymphoma patients.
II. To evaluate the clinical response rate in B cell lymphoma patients treated with MDX-010.
SECONDARY OBJECTIVES:
- To evaluate the phenotype and function of memory T cells before and after treatment with MDX-010 by:
- Quantitation and phenotypic characterization of peripheral blood and tumor infiltrating T-cells, including cluster of differentiation (CD)4+CD25+ regulatory T cells.
- Measurement of tumor-specific T cells in peripheral blood lymphocytes.
- Measuring proliferation of memory T cells in response to recall antigens (tetanus toxoid and keyhole limpet hemocyanin [KLH]).
II. Measurement of anti-tumor antibodies in serum pre- and post-therapy. III. To evaluate the time to progression. IV. To evaluate the duration of response to treatment with MDX-010.
OUTLINE: This is a multicenter, open-label, phase I, dose-escalation study followed by a phase II study. Patients are grouped according to prior treatment with a vaccine therapy for lymphoma (yes vs no).
PHASE I: Patients receive anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody (MDX-010) IV over 90 minutes on day 1. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 6 patients from each group receive escalating doses of MDX-010 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.
PHASE II: Patients receive MDX-010 as in phase I at the MTD.
Patients are followed at 1 and 4 months and then every 6 months for up to 2 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (ipilimumab) | Experimental | Biological: ipilimumab, Other: laboratory biomarker analysisPHASE I: Patients receive MDX-010 IV over 90 minutes on day 1. Treatment repeats every 28 days for a total of 4 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 6 patients from each group receive escalating doses of MDX-010 until the MTD is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity. PHASE II: Patients receive MDX-010 as in phase I at the MTD. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Histologic proof of recurring or residual follicular B-cell non-Hodgkin's lymphoma (grade I or II), by Revised European American Lymphoma Classification (REAL) or World Health Organization (WHO) classifications which has relapsed or persisted after 3 or fewer conventional therapies, including chemotherapy or monoclonal antibody therapy; note: all patients with previously treated B-cell lymphomas of any histology with the exception of small lymphocytic lymphoma/chronic lymphocytic leukemia (CLL) are eligible
- Tumor measurable by computed tomography (CT) scans (at least one pathologic node measuring 2.0 x 2.0 cm, or 2 nodes measuring > 1.5 x 1.5 cm after collection of tumor for immunologic analyses)
- At least one prior treatment regimen but no more than 3 prior chemotherapy regimens; patients previously treated with monoclonal antibodies or radiotherapy to a single site will be eligible; these therapies will be considered prior treatment regimens but will not be considered as prior chemotherapy; tumor vaccines will not be counted as prior therapies, as all such agents are investigational
- Absolute neutrophil count (ANC) >= 1000/uL
- Platelets (PLT) >= 75,000/uL
Key exclusion criteria (17 listed)
- Known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2, 3, or 4
- Any uncontrolled infection, hepatitis C virus (HCV)+ (unless HCV ribonucleic acid [RNA]-negative by polymerase chain reaction [PCR]) or hepatitis B surface antigen (HBsAg)+, or human immunodeficiency virus (HIV) positive patients or patients with known immune deficiency states
- Previous MDX-010 therapy regardless of interval since last treatment
- Prior treatment with fludarabine or 2-chlorodeoxyadenosine =< 12 months prior to registration
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 |
|---|---|---|
| ipilimumabAlso: anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody, MDX-010, MDX-CTLA-4, monoclonal antibody CTLA-4Given IV | Biological | Treatment (ipilimumab) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (ipilimumab) |
Primary outcome
Number of Overall Confirmed Responses(Complete Response or Partial Response)
Time frame: From registration to month 7
Confirmed response is at least a 50% decrease in the sum of the products of the greatest diameters (SPD) of the six largest dominant nodes or nodal masses and no increase in the size of other nodes, liver, or spleen and splenic and hepatic nodules must regress by at least 50% in the SPD and no new sites of disease.
7 secondary outcomes
Time to Progression (Phase 2)
Time frame: From registration to progression (up to 2 years)
Overall Survival (Phase 2)
Time frame: From registration to death (up to 2 years)
Duration of Response (Phase 2)
Time frame: From response to progression (up to 2 years)
Mean Change in % of CD3+CD4+ for Marker HLA-DR+
Time frame: Before treatment to 1 month after therapy initiation
Mean Change in % of CD3+CD4- for Marker HLA-DR+
Time frame: Before treatment to 1 month after therapy initiation
Mean Change in % of CD3+CD4+ for Marker CD45RO+
Time frame: Before treatment to 1 month after therapy initiation
Mean Change in % of CD3+CD4- for the Marker CD45RO+
Time frame: Before treatment to 1 month after therapy initiation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Stephen Ansell principal investigator
Mayo Clinic
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ipilimumab and laboratory biomarker analysis in people with Adult Grade III Lymphomatoid Granulomatosis and B-cell Chronic Lymphocytic Leukemia, 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 13 inclusion and 17 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 30 May 2014. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Oct 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Overall Confirmed Responses(Complete Response or Partial Response) (time frame: From registration to month 7). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 May 2014; AzTrials last refreshed its copy on 6 Nov 2026.