search
Back to results

MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma

Primary Purpose

Adult Grade III Lymphomatoid Granulomatosis, B-cell Chronic Lymphocytic Leukemia, Cutaneous B-cell Non-Hodgkin Lymphoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
ipilimumab
laboratory biomarker analysis
Sponsored by
National Cancer Institute (NCI)
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Adult Grade III Lymphomatoid Granulomatosis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (ipilimumab)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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
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
Mean Change in % of CD3+CD4+ for Marker CD45RO+
Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy
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

Full Information

First Posted
August 4, 2004
Last Updated
May 22, 2014
Sponsor
National Cancer Institute (NCI)
search

1. Study Identification

Unique Protocol Identification Number
NCT00089076
Brief Title
MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma
Official Title
Phase I/II Study of Anti-CTLA-4 Monoclonal Antibody (MDX-010) in B-cell Non-Hodgkin's Lymphoma
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Terminated
Study Start Date
June 2004 (undefined)
Primary Completion Date
July 2008 (Actual)
Study Completion Date
October 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Cancer Institute (NCI)

4. Oversight

5. Study Description

Brief 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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, 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 Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin 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, Refractory Hairy Cell Leukemia, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Testicular Lymphoma, Waldenström Macroglobulinemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (ipilimumab)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
ipilimumab
Other Intervention Name(s)
anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody, MDX-010, MDX-CTLA-4, monoclonal antibody CTLA-4
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
laboratory biomarker analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Number of Overall Confirmed Responses(Complete Response or Partial Response)
Description
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.
Time Frame
From registration to month 7
Secondary Outcome Measure Information:
Title
Time to Progression (Phase 2)
Description
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.
Time Frame
From registration to progression (up to 2 years)
Title
Overall Survival (Phase 2)
Description
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.
Time Frame
From registration to death (up to 2 years)
Title
Duration of Response (Phase 2)
Description
Duration of response will be calculated from the documentation of confirmed response until the date of progression in the subset of patients who respond.
Time Frame
From response to progression (up to 2 years)
Title
Mean Change in % of CD3+CD4+ for Marker HLA-DR+
Description
Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy
Time Frame
Before treatment to 1 month after therapy initiation
Title
Mean Change in % of CD3+CD4- for Marker HLA-DR+
Description
Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy
Time Frame
Before treatment to 1 month after therapy initiation
Title
Mean Change in % of CD3+CD4+ for Marker CD45RO+
Description
Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy
Time Frame
Before treatment to 1 month after therapy initiation
Title
Mean Change in % of CD3+CD4- for the Marker CD45RO+
Description
Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy
Time Frame
Before treatment to 1 month after therapy initiation

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Stephen Ansell
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Learn more about this trial

MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma

We'll reach out to this number within 24 hrs