NCT00089076

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.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
18

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jun 2004

Longer than P75 for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

June 1, 2004

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

August 4, 2004

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 5, 2004

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2008

Completed
1.3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2009

Completed
3.1 years until next milestone

Results Posted

Study results publicly available

October 19, 2012

Completed
Last Updated

May 30, 2014

Status Verified

December 1, 2012

Enrollment Period

4.1 years

First QC Date

August 4, 2004

Results QC Date

May 11, 2012

Last Update Submit

May 22, 2014

Conditions

Outcome Measures

Primary Outcomes (1)

  • 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.

    From registration to month 7

Secondary Outcomes (7)

  • Time to Progression (Phase 2)

    From registration to progression (up to 2 years)

  • Overall Survival (Phase 2)

    From registration to death (up to 2 years)

  • Duration of Response (Phase 2)

    From response to progression (up to 2 years)

  • Mean Change in % of CD3+CD4+ for Marker HLA-DR+

    Before treatment to 1 month after therapy initiation

  • Mean Change in % of CD3+CD4- for Marker HLA-DR+

    Before treatment to 1 month after therapy initiation

  • +2 more secondary outcomes

Study Arms (1)

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.

Biological: ipilimumabOther: laboratory biomarker analysis

Interventions

ipilimumabBIOLOGICAL

Given IV

Also known as: anti-cytotoxic T-lymphocyte-associated antigen-4 monoclonal antibody, MDX-010, MDX-CTLA-4, monoclonal antibody CTLA-4
Treatment (ipilimumab)

Correlative studies

Treatment (ipilimumab)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +2 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-CellIntraocular LymphomaLymphoma, B-Cell, Marginal ZoneBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinHodgkin DiseaseLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaLymphoma, FollicularLymphoma, Mantle-CellLeukemia, Hairy CellWaldenstrom Macroglobulinemia

Interventions

IpilimumabCTLA-4 Antigen

Condition Hierarchy (Ancestors)

Leukemia, B-CellLeukemia, LymphoidLeukemiaNeoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLymphomaEye NeoplasmsNeoplasms by SiteLymphoma, B-CellEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulinsImmune Checkpoint ProteinsCostimulatory and Inhibitory T-Cell ReceptorsReceptors, ImmunologicReceptors, Cell SurfaceMembrane ProteinsAntigens, Differentiation, T-LymphocyteAntigens, DifferentiationAntigens, SurfaceAntigensBiological FactorsBiomarkers

Results Point of Contact

Title
Dr. Stephen Ansell
Organization
Mayo Clinic

Study Officials

  • Stephen Ansell

    Mayo Clinic

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 4, 2004

First Posted

August 5, 2004

Study Start

June 1, 2004

Primary Completion

July 1, 2008

Study Completion

October 1, 2009

Last Updated

May 30, 2014

Results First Posted

October 19, 2012

Record last verified: 2012-12

Locations