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

NCT00438880 | Completed Phase 1 Results

• 3 other identifiers: LS0382NCI-2009-01275P30CA015083
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Adult Non-Hodgkin Lymphoma; Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue; Nodal Marginal Zone Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Splenic Marginal Zone Lymphoma; Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (2)

• Maximum Tolerated Dose of CpG 7909 as Determined Using the Number of Participants With a DLT at Each Dose Level

  Participants will be treated in cohorts of 6 patients at each dose level of CpG 7909 (0.08 mg/kg, 0.16 mg/kg, 0.32 mg/kg, 0.48 mg/kg) and observed for at least 10 weeks post treatment. If at most one of the 6 patients experiences a dose limiting toxicity (DLT), a new cohort of 6 patients will be treated at the next higher dose level. A DLT for this study is defined as patients with one of the following: * Absolute neutrophil counts or platelet counts below 10\*10\^9/L for 14 days * Absolute neutrophil counts greater than 0.5 or less than 1\*10\^9/L * Platelet counts greater than 10 or less than 50\*10\^9/L for 28 days. * Any grade 3 non-hematologic toxicity not explainable by another obvious cause as assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v3.0. We are reporting the number of DLTs at each of the dose levels. The maximum tolerated dose will be 0.48 mg/kg or the largest dose level where 1 or fewer participants reports a dose limiting toxicity.

  at least 10 weeks post treatment up to 3 months.

• Tumor Response

  Complete Response (CR): * No measurable or nonmeasurable disease. * No symptoms of Lymphoma. * Non-palpable spleen, if palpable at baseline. * Histologically negative bone marrow, if positive at baseline. * All nodes \<1.5 cm in transverse diameter. Partial Response (PR): * greater than 50% decrease from baseline in the sum of the products of the longest perpendicular diameters of the six largest dominant lesions. * No new lesions We are reporting the number of participants that attained a status of CR or PR.

  Evaluations occur every three months up to a year

Secondary Outcomes (2)

• Progression-free Survival

  Up to 1 year from treatment start date

• Duration of Response

  Up to 1 year from treatment start date

Study Arms (1)

Arm I

EXPERIMENTAL

See Detailed Description

Drug: Agatolimod Sodium; Radiation: Indium In-111 Ibritumomab Tiuxetan; Other: Laboratory Biomarker Analysis; Procedure: Radionuclide Imaging; Biological: Rituximab; Procedure: Single Photon Emission Computed Tomography; Radiation: Yttrium Y-90 Ibritumomab Tiuxetan

Interventions

Agatolimod Sodium DRUG

Given IV

Also known as: (3'-5')d(P-thio)(T-C-G-T-C-G-T-T-T-T-G-T-C-G-T-T-T-T-G-T-C-G-T-T) Tricosasodium Salt, CpG 7909, PF-3512676, ProMune

Arm I

Indium In-111 Ibritumomab Tiuxetan RADIATION

Given IV

Also known as: IDEC In2B8, IDEC-In2B8, In 111 Ibritumomab Tiuxetan, In 111 Zevalin, indium In 111 ibritumomab tiuxetan

Arm I

Laboratory Biomarker Analysis OTHER

Correlative study

Arm I

Radionuclide Imaging PROCEDURE

Undergo imaging scans

Also known as: nuclear medicine scan, radioimaging, Radionuclide Scanning, Scan, SCINTIGRAPHY

Arm I

Rituximab BIOLOGICAL

Given IV

Also known as: BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, IDEC-102, IDEC-C2B8, IDEC-C2B8 Monoclonal Antibody, MabThera, Monoclonal Antibody IDEC-C2B8, PF-05280586, Rituxan, Rituximab Biosimilar BI 695500, Rituximab Biosimilar PF-05280586, Rituximab Biosimilar RTXM83, RTXM83

Arm I

Single Photon Emission Computed Tomography PROCEDURE

Undergo imaging scans

Also known as: Medical Imaging, Single Photon Emission Computed Tomography, Single Photon Emission Tomography, single-photon emission computed tomography, SPECT, SPECT imaging, SPECT SCAN, SPET, tomography, emission computed, single photon, Tomography, Emission-Computed, Single-Photon

Arm I

Yttrium Y-90 Ibritumomab Tiuxetan RADIATION

Given IV

Also known as: IDEC-Y2B8, IDEC-Y2B8 monoclonal antibody, Y 90 Ibritumomab Tiuxetan, Y 90 Zevalin, Yttrium Y 90 Ibritumomab Tiuxetan, yttrium Y90 ibritumomab tiuxetan

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• The following histologic types by REAL classification and International Working Formulation (IWF) when applicable: Diffuse large cell; Transformed lymphoma
• 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)
• There is no limit on the number of prior therapies (patients who have previously received rituximab are eligible)
• Bi-dimensionally measurable disease: The patients must have \>= 1 lesion that has a single diameter of \>= 2 cm
• Absolute neutrophil count \>= 1500/mm\^3
• Platelet count \>= 150,000
• Total lymphocyte count \< 5000/mm\^3 only for patients with small lymphocytic lymphoma
• HGB \>= 8
• 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
• ECOG performance status (PS) 0, 1, or 2
• Expected survival \>= 3 months
• Willingness to provide all biologic specimens as required by the protocol
• Total bilirubin =\< 2 x ULN mg/dL (if abnormal, direct bilirubin =\< 1.5 x ULN)

You may not qualify if:

• Prior myeloablative therapies with autologous or allogeneic bone marrow transplantation or peripheral blood stem cell support
• Prior radioimmunotherapy including Y-90 Zevalin or 131-Iodine anti-B1 antibody or Lym-1
• Presence of CNS lymphoma
• Serious non-malignant disease such as active infection or other condition which in the opinion of the investigator would compromise other protocol objectives
• Major surgery other than diagnostic surgery =\< 4 weeks prior to registration
• Another active primary malignancy
• Known HAMA/HACA (Human anti-mouse or anti-chimeric antibodies)
• Myelodysplastic syndrome or marrow chromosomal changes suggesting myelodysplasia
• 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 \[IUD\], surgical sterilization, abstinence, etc.)
• Failed stem cell collection
• Marrow cellularity =\< 15% (as determined on all bone marrow samples)
• 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)
• G-CSF or GM-CSF therapy =\< 1 week prior to study registration (pegylated filgrastim =\< 3 weeks)

Sponsors & Collaborators

• Mayo Clinic: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

University of Iowa/Holden Comprehensive Cancer Center

Iowa City, Iowa, 52242, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Lymphoma, B-Cell, Marginal Zone; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Follicular; Lymphoma, Mantle-Cell; Leukemia, Lymphocytic, Chronic, B-Cell; Waldenstrom Macroglobulinemia

Interventions

ProMune; Indium; Rituximab; X-Rays; Photons; ibritumomab tiuxetan

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Metals, Heavy; Elements; Inorganic Chemicals; Metals; Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Electromagnetic Radiation; Electromagnetic Phenomena; Magnetic Phenomena; Physical Phenomena; Radiation; Radiation, Ionizing; Elementary Particles; Light; Optical Phenomena; Radiation, Nonionizing

Results Point of Contact

• Title: Thomas E. Witzig, M.D.
• Organization: Mayo Clinic Cancer Center

witzig.thomas@mayo.edu

Study Officials

• Thomas Witzig

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

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

Study Record Dates

• First Submitted: February 20, 2007
• First Posted: February 22, 2007
• Study Start: October 1, 2004
• Primary Completion: October 1, 2010
• Study Completion: November 1, 2014
• Last Updated: February 4, 2016
• Results First Posted: September 1, 2014

Record last verified: 2015-09

Locations

US (2)