- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00089076
MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma
Phase I/II Study of Anti-CTLA-4 Monoclonal Antibody (MDX-010) in B-cell Non-Hodgkin's Lymphoma
Study Overview
Status
Conditions
- Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
- Nodal Marginal Zone B-cell Lymphoma
- Recurrent Adult Burkitt Lymphoma
- Recurrent Adult Diffuse Large Cell Lymphoma
- Recurrent Adult Diffuse Mixed Cell Lymphoma
- Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
- Recurrent Adult Immunoblastic Large Cell Lymphoma
- Recurrent Adult Lymphoblastic Lymphoma
- Recurrent Grade 1 Follicular Lymphoma
- Recurrent Grade 2 Follicular Lymphoma
- Recurrent Mantle Cell Lymphoma
- Recurrent Marginal Zone Lymphoma
- Splenic Marginal Zone Lymphoma
- Waldenström Macroglobulinemia
- Cutaneous B-cell Non-Hodgkin Lymphoma
- Intraocular Lymphoma
- Recurrent Adult Grade III Lymphomatoid Granulomatosis
- Recurrent Adult Hodgkin Lymphoma
- Small Intestine Lymphoma
- Testicular Lymphoma
- B-cell Chronic Lymphocytic Leukemia
- Refractory Hairy Cell Leukemia
- Adult Grade III Lymphomatoid Granulomatosis
Intervention / Treatment
Detailed Description
PRIMARY OBJECTIVES:
I. 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:
I. 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 Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Minnesota
-
Rochester, Minnesota, United States, 55905
- Mayo Clinic
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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)
- 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
Exclusion Criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: Treatment (ipilimumab)
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. |
Correlative studies
Given IV
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
From registration to month 7
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Time to Progression (Phase 2)
Time Frame: From registration to progression (up to 2 years)
|
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.
|
From registration to progression (up to 2 years)
|
Overall Survival (Phase 2)
Time Frame: From registration to death (up to 2 years)
|
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.
|
From registration to death (up to 2 years)
|
Duration of Response (Phase 2)
Time Frame: From response to progression (up to 2 years)
|
Duration of response will be calculated from the documentation of confirmed response until the date of progression in the subset of patients who respond.
|
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
|
Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy
|
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
|
Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy
|
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
|
Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy
|
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
|
Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy
|
Before treatment to 1 month after therapy initiation
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Stephen Ansell, Mayo Clinic
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Cardiovascular Diseases
- Vascular Diseases
- Virus Diseases
- Infections
- Immune System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Lymphoproliferative Disorders
- Lymphatic Diseases
- Immunoproliferative Disorders
- Neoplasms by Site
- Disease Attributes
- Hematologic Diseases
- Hemorrhagic Disorders
- Hemostatic Disorders
- Paraproteinemias
- Blood Protein Disorders
- DNA Virus Infections
- Tumor Virus Infections
- Neoplasms, Plasma Cell
- Precancerous Conditions
- Leukemia, Lymphoid
- Epstein-Barr Virus Infections
- Herpesviridae Infections
- Leukemia, B-Cell
- Eye Neoplasms
- Lymphoma, T-Cell
- Lymphoma
- Lymphoma, Follicular
- Lymphoma, B-Cell
- Lymphoma, Large B-Cell, Diffuse
- Leukemia
- Hodgkin Disease
- Recurrence
- Lymphoma, Non-Hodgkin
- Burkitt Lymphoma
- Lymphoma, Mantle-Cell
- Lymphoma, B-Cell, Marginal Zone
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- Lymphoma, Large-Cell, Immunoblastic
- Plasmablastic Lymphoma
- Waldenstrom Macroglobulinemia
- Leukemia, Lymphocytic, Chronic, B-Cell
- Lymphomatoid Granulomatosis
- Lymphoma, Extranodal NK-T-Cell
- Intraocular Lymphoma
- Leukemia, Hairy Cell
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antineoplastic Agents
- Immunologic Factors
- Immune Checkpoint Inhibitors
- Antibodies
- Immunoglobulins
- Antibodies, Monoclonal
- Antineoplastic Agents, Immunological
- Ipilimumab
Other Study ID Numbers
- NCI-2012-02784 (REGISTRY: CTRP (Clinical Trial Reporting Program))
- P30CA015083 (U.S. NIH Grant/Contract)
- U01CA069912 (U.S. NIH Grant/Contract)
- MC0312 (OTHER: Mayo Clinic)
- 6359 (OTHER: CTEP)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)CompletedAnn Arbor Stage II Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue | Ann Arbor Stage I Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue | Extranodal Marginal Zone LymphomaUnited States
-
University of WashingtonGenentech, Inc.RecruitingMarginal Zone Lymphoma | Non-Hodgkin Lymphoma | Grade 1 Follicular Lymphoma | Grade 2 Follicular Lymphoma | Grade 3a Follicular Lymphoma | Indolent B-Cell Non-Hodgkin Lymphoma | Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue | Refractory Extranodal Marginal Zone...United States
-
Narendranath EpperlaNot yet recruitingRecurrent Mantle Cell Lymphoma | Recurrent Marginal Zone Lymphoma | Refractory Mantle Cell Lymphoma | Refractory Marginal Zone Lymphoma | Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue | Refractory Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid... and other conditionsUnited States
-
University of WashingtonMillennium Pharmaceuticals, Inc.Active, not recruitingFollicular Lymphoma | Waldenstrom Macroglobulinemia | Mantle Cell Lymphoma | Marginal Zone Lymphoma | Chronic Lymphocytic Leukemia | Lymphoplasmacytic Lymphoma | Small Lymphocytic Lymphoma | Recurrent Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue | Refractory Extranodal Marginal...United States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...Genentech, Inc.; Pharmacyclics LLC.RecruitingNon-Hodgkin's Lymphoma | Indolent Non-hodgkin Lymphoma | Ann Arbor Stage II Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue | Ann Arbor Stage II Follicular Lymphoma | Ann Arbor Stage II Nodal Marginal Zone Lymphoma | Ann Abor Stage III B-Cell Non-Hodgkin Lymphoma | Ann Arbor... and other conditionsUnited States
-
Yazeed SawalhaWithdrawnRecurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Mantle Cell Lymphoma | Recurrent Marginal Zone Lymphoma | Refractory B-Cell Non-Hodgkin Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma | Recurrent Grade 3a Follicular Lymphoma | Refractory Grade 1 Follicular... and other conditions
-
Robert LowskyNational Cancer Institute (NCI)CompletedExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue | Nodal Marginal Zone B-cell Lymphoma | Recurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Marginal Zone Lymphoma | Splenic Marginal Zone Lymphoma | Recurrent Small Lymphocytic...United States
-
National Cancer Institute (NCI)WithdrawnExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue | Nodal Marginal Zone B-cell Lymphoma | Recurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Mantle Cell Lymphoma | Recurrent Marginal Zone Lymphoma | Splenic Marginal Zone LymphomaUnited States
-
Arbeitsgemeinschaft medikamentoese TumortherapieHoffmann-La Roche; LipomedCompletedLymphoma of Mucosa-Associated Lymphoid TissueAustria
-
Mayo ClinicNational Cancer Institute (NCI)CompletedRecurrent Grade 1 Follicular Lymphoma | Recurrent Grade 2 Follicular Lymphoma | Recurrent Grade 3 Follicular Lymphoma | Recurrent Marginal Zone Lymphoma | Waldenstrom Macroglobulinemia | Refractory B-Cell Non-Hodgkin Lymphoma | Recurrent Small Lymphocytic Lymphoma | Recurrent B-Cell Non-Hodgkin Lymphoma and other conditionsUnited States
Clinical Trials on laboratory biomarker analysis
-
ECOG-ACRIN Cancer Research GroupNational Cancer Institute (NCI)CompletedProstate Cancer
-
Children's Oncology GroupNational Cancer Institute (NCI)Completed
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Active, not recruitingLeukemia | Acute Lymphoblastic Leukemia | Acute Promyelocytic LeukemiaUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedUntreated Adult Acute Lymphoblastic Leukemia | Untreated Childhood Acute Lymphoblastic LeukemiaUnited States, Canada, Australia, New Zealand, Puerto Rico, Switzerland
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedChildhood Acute Lymphoblastic Leukemia in Remission | Recurrent Childhood Acute Lymphoblastic LeukemiaUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedLung CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)Completed
-
Children's Oncology GroupNational Cancer Institute (NCI)WithdrawnClear Cell Renal Cell Carcinoma | Rhabdoid Tumor of the Kidney | Congenital Mesoblastic Nephroma | Childhood Kidney NeoplasmUnited States
-
Gynecologic Oncology GroupNational Cancer Institute (NCI)WithdrawnBreast Carcinoma | BRCA1 Mutation Carrier | BRCA2 Mutation CarrierUnited States
-
Children's Oncology GroupNational Cancer Institute (NCI)CompletedWilms Tumor and Other Childhood Kidney TumorsUnited States