MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma

This study has been terminated.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00089076
First received: August 4, 2004
Last updated: May 22, 2014
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
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
Biological: ipilimumab
Other: laboratory biomarker analysis
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Study of Anti-CTLA-4 Monoclonal Antibody (MDX-010) in B-cell Non-Hodgkin's Lymphoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Number of Overall Confirmed Responses(Complete Response or Partial Response) [ Time Frame: From registration to month 7 ] [ Designated as safety issue: No ]
    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) [ Time Frame: From registration to progression (up to 2 years) ] [ Designated as safety issue: No ]
    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) [ Time Frame: From registration to death (up to 2 years) ] [ Designated as safety issue: No ]
    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) [ Time Frame: From response to progression (up to 2 years) ] [ Designated as safety issue: No ]
    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+ [ Time Frame: Before treatment to 1 month after therapy initiation ] [ Designated as safety issue: No ]
    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+ [ Time Frame: Before treatment to 1 month after therapy initiation ] [ Designated as safety issue: No ]
    Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy

  • Mean Change in % of CD3+CD4+ for Marker CD45RO+ [ Time Frame: Before treatment to 1 month after therapy initiation ] [ Designated as safety issue: No ]
    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+ [ Time Frame: Before treatment to 1 month after therapy initiation ] [ Designated as safety issue: No ]
    Flow cytometric analysis of T-cell surface markers before and 1 month after initiation therapy


Enrollment: 18
Study Start Date: June 2004
Study Completion Date: October 2009
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Biological: ipilimumab
Given IV
Other Names:
  • anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody
  • MDX-010
  • MDX-CTLA-4
  • monoclonal antibody CTLA-4
Other: laboratory biomarker analysis
Correlative studies

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00089076

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Investigators
Principal Investigator: Stephen Ansell Mayo Clinic
  More Information

No publications provided

Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00089076     History of Changes
Other Study ID Numbers: NCI-2012-02784, NCI-2012-02784, MC0312, 6359, P30CA015083, U01CA069912
Study First Received: August 4, 2004
Results First Received: May 11, 2012
Last Updated: May 22, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Burkitt Lymphoma
Hodgkin Disease
Intraocular Lymphoma
Leukemia
Leukemia, Hairy Cell
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, Lymphoid
Lymphoma
Lymphoma, B-Cell
Lymphoma, B-Cell, Marginal Zone
Lymphoma, Extranodal NK-T-Cell
Lymphoma, Follicular
Lymphoma, Large B-Cell, Diffuse
Lymphoma, Large-Cell, Immunoblastic
Lymphoma, Mantle-Cell
Lymphoma, Non-Hodgkin
Lymphomatoid Granulomatosis
Waldenstrom Macroglobulinemia
Blood Protein Disorders
Cardiovascular Diseases
DNA Virus Infections
Epstein-Barr Virus Infections
Eye Neoplasms
Hematologic Diseases
Hemorrhagic Disorders
Hemostatic Disorders
Herpesviridae Infections
Immune System Diseases
Immunoproliferative Disorders
Leukemia, B-Cell

ClinicalTrials.gov processed this record on October 21, 2014