TheranosticTrials.org

Clinical Trial · NCT00438880

Agatolimod Sodium, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Recurrent or Refractory Non-Hodgkin Lymphoma

Overview

RATIONALE: Biological therapies, such as agatolimod sodium, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Radiolabeled monoclonal antibodies, such as yttrium Y 90 ibritumomab tiuxetan, can find cancer cells and carry cancer-killing substances to them without harming normal cells. Giving agatolimod sodium together with rituximab and yttrium Y 90 ibritumomab tiuxetan may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of agatolimod sodium when given together with rituximab and yttrium Y 90 ibritumomab tiuxetan and to see how well it works in treating patients with recurrent or refractory non-Hodgkin lymphoma.

Sponsor

Mayo Clinic

Phase

Phase 1/2

Contacts

Thomas Witzig (PRINCIPAL_INVESTIGATOR)

ClinicalTrials.gov

NCT00438880

Drug / Compound

ibritumomab tiuxetan

Isotope(s):
Target(s):
  • cd20
Ligand Class: Antibodies
Chelator: tiuxetan

ibritumomab tiuxetan

Isotope(s):
Target(s):
  • cd20
Ligand Class: Antibodies
Chelator: tiuxetan

Eligibility

Inclusion

  • Platelet count \>= 150,000
  • Total bilirubin =\< 2 x ULN mg/dL (if abnormal, direct bilirubin =\< 1.5 x ULN)
  • HGB \>= 8
  • There is no limit on the number of prior therapies (patients who have previously received rituximab are eligible)
  • Less than 25% bone marrow involvement of cellular marrow with lymphoma as determined by bilateral bone marrow aspirate and biopsy (the percent involvement should be estimated by the hematopathologist using all of the biopsy material)
  • Total lymphocyte count \< 5000/mm\^3 only for patients with small lymphocytic lymphoma
  • Expected survival \>= 3 months
  • Absolute neutrophil count \>= 1500/mm\^3
  • ECOG performance status (PS) 0, 1, or 2
  • Willingness to provide all biologic specimens as required by the protocol
  • Bi-dimensionally measurable disease: The patients must have \>= 1 lesion that has a single diameter of \>= 2 cm
  • The following histologic types by REAL classification and International Working Formulation (IWF) when applicable (NOTE: Closed to accrual as of 10/29/07): Small lymphocytic lymphoma; Lymphoplasmacytoid lymphoma; Follicular center lymphoma, follicular grades 1, 2, and 3; Extranodal marginal zone B cell lymphoma of MALT type; Nodal marginal zone B cell lymphoma
  • Biopsy-proven relapsed, refractory, or residual CD20+ non-Hodgkin's lymphomas; previous biopsies =\<6 months prior to treatment on this protocol will be acceptable as long as there has not been intervening therapy; if the patient has received therapy for NHL between the time of the last biopsy and this protocol, then a re-biopsy is necessary
  • The following histologic types by REAL classification and International Working Formulation (IWF) when applicable: Diffuse large cell; Transformed lymphoma

Exclusion

  • Known to have lymphoma related to HIV or AIDS (these patients are excluded because it is unknown what effects prolonged B-cell depletion will have on these patient's immune system)
  • Abnormal renal function (serum creatinine \> 2 mg/dL)
  • Another active primary malignancy
  • Myelosuppressive chemotherapy =\< 3 weeks prior to study registration (=\< 6 weeks if rituximab, nitrosourea, or Mitomycin C)
  • Pregnant women
  • Known HAMA/HACA (Human anti-mouse or anti-chimeric antibodies)
  • Received prior external beam radiation therapy to \> 25% of active bone marrow
  • G-CSF or GM-CSF therapy =\< 1 week prior to study registration (pegylated filgrastim =\< 3 weeks)
  • Serious non-malignant disease such as active infection or other condition which in the opinion of the investigator would compromise other protocol objectives
  • Failed stem cell collection
  • Nursing women
  • Skin rash (such as Stevens-Johnson's syndrome or toxic epidermal necrolysis) with prior rituximab therapy should not be entered on this study because of the risk of reoccurrence of that skin toxicity
  • Marrow cellularity =\< 15% (as determined on all bone marrow samples)
  • Corticosteroid therapy at the time the patient enters the protocol; patients using prednisone or its equivalent for adrenal failure or using \< 20mg of prednisone/day for other benign causes are accepted
  • Major surgery other than diagnostic surgery =\< 4 weeks prior to registration
  • Myelodysplastic syndrome or marrow chromosomal changes suggesting myelodysplasia
  • Presence of CNS lymphoma
  • Prior myeloablative therapies with autologous or allogeneic bone marrow transplantation or peripheral blood stem cell support
  • Men or women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragm, birth control pills, injections, intrauterine device \[IUD\], surgical sterilization, abstinence, etc.)
  • Prior radioimmunotherapy including Y-90 Zevalin or 131-Iodine anti-B1 antibody or Lym-1
  • Pre-existent clinical autoimmune or antibody mediated diseases, including systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome, and autoimmune thrombocytopenia (patients that have no clinical symptoms of these diseases, but merely have previously detected antibodies are eligible)