MDX-010 in Treating Patients With Recurrent or Refractory Lymphoma

National Cancer Institute (NCI) logo

National Cancer Institute (NCI)

Status and phase

Terminated
Phase 2
Phase 1

Conditions

Waldenström Macroglobulinemia
Recurrent Adult Hodgkin Lymphoma
Cutaneous B-cell Non-Hodgkin Lymphoma
Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue
Splenic Marginal Zone Lymphoma
Recurrent Adult Diffuse Small Cleaved Cell Lymphoma
Recurrent Grade 2 Follicular Lymphoma
Recurrent Adult Diffuse Large Cell Lymphoma
Recurrent Marginal Zone Lymphoma
B-cell Chronic Lymphocytic Leukemia
Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Grade III Lymphomatoid Granulomatosis
Recurrent Adult Diffuse Mixed Cell Lymphoma
Nodal Marginal Zone B-cell Lymphoma
Recurrent Adult Burkitt Lymphoma
Small Intestine Lymphoma
Recurrent Grade 1 Follicular Lymphoma
Testicular Lymphoma
Recurrent Mantle Cell Lymphoma
Recurrent Adult Immunoblastic Large Cell Lymphoma
Recurrent Adult Lymphoblastic Lymphoma
Refractory Hairy Cell Leukemia
Intraocular Lymphoma

Treatments

Other: laboratory biomarker analysis
Biological: ipilimumab

Study type

Interventional

Funder types

NIH

Identifiers

NCT00089076
P30CA015083 (U.S. NIH Grant/Contract)
MC0312 (Other Identifier)
U01CA069912 (U.S. NIH Grant/Contract)
6359 (Other Identifier)
NCI-2012-02784 (Registry Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment

18 patients

Sex

All

Ages

18+ years old

Volunteers

No 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

Trial design

18 participants in 1 patient group

Treatment (ipilimumab)
Experimental group
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.
Treatment:
Biological: ipilimumab
Other: laboratory biomarker analysis

Trial contacts and locations

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Data sourced from clinicaltrials.gov

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