CpG 7909, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Non-Hodgkin's Lymphoma That is Recurrent or Did Not Respond to Previous Treatment - Full Text View

Sponsors and Collaborators:	Mayo Clinic National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00438880

Purpose

RATIONALE: Biological therapies, such as CpG 7909, may stimulate the immune system in different ways and stop cancer cells from growing. Monoclonal antibodies, such as rituximab and yttrium Y 90 ibritumomab tiuxetan, 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. Giving CpG 7909 together with monoclonal antibodies may kill more cancer cells.

PURPOSE: This phase I trial is studying the side effects and best dose of CpG 7909 when given together with rituximab and yttrium Y 90 ibritumomab tiuxetan in treating patients with non-Hodgkin's lymphoma that is recurrent or did not respond to previous treatment.

Condition	Intervention	Phase
Lymphoma	Biological: rituximab Drug: agatolimod sodium Other: biomarker analysis Other: flow cytometry Other: immunologic technique Other: laboratory biomarker analysis Procedure: radionuclide imaging Procedure: single photon emission computed tomography Radiation: indium In 111 ibritumomab tiuxetan Radiation: yttrium Y 90 ibritumomab tiuxetan	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	A Phase I/II Trial of CpG 7909, Rituximab Immunotherapy, and Y-90 Zevalin Radioimmunotherapy for Patients With Previously Treated CD20+ Non-Hodgkin Lymphoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lymphoma Nuclear Scans Radiation Therapy

Drug Information available for: Indium in 111 oxyquinoline Rituximab Ibritumomab tiuxetan Agatolimod sodium

U.S. FDA Resources

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

Primary Outcome Measures:

Toxicity [ Designated as safety issue: Yes ]
Immunostimulation (optimal immunological dose) [ Designated as safety issue: No ]
Change in fraction of injected activity [ Designated as safety issue: No ]
Tumor response [ Designated as safety issue: No ]

Secondary Outcome Measures:

Response rate (complete response [CR], CR unconfirmed, partial response) [ Designated as safety issue: No ]
Human antimouse antibodies and human antichimeric antibodies [ Designated as safety issue: No ]
Event-free survival [ Designated as safety issue: No ]
Overall survival [ Designated as safety issue: No ]
Progression-free survival [ Designated as safety issue: No ]
Duration of response [ Designated as safety issue: No ]

Estimated Enrollment:	63
Study Start Date:	October 2004
Estimated Primary Completion Date:	November 2007 (Final data collection date for primary outcome measure)

Detailed Description:

OBJECTIVES:

Primary

Determine the maximum tolerated dose of CpG 7909 when administered in combination with rituximab and yttrium 90 ibritumomab in patients with CD20+ recurrent or refractory non-Hodgkin's lymphoma. (Phase I)
Assess the toxicity of this regimen in these patients. (Phase I)

Secondary

Determine the response rate (complete response [CR], CR unconfirmed, and partial response [PR]) in patients treated with this regimen. (Phase I)
Compare the biodistribution of indium In 111 ibritumomab tiuxetan radioimmunoconjugate scans before and after treatment with CpG 7909. (Phase I)
Determine the human antimouse antibody and/or human antichimeric antibody rate in patients treated with this regimen. (Phase I)
Determine if CpG 7909, when given in combination with rituximab and yttrium Y 90 ibritumomab tiuxetan, can stimulate immune effector cells in the blood and tumor tissue of these patients. (Phase I)
Assess the overall response rate (CR and PR) of this regimen in relapsed diffuse large B cell lymphoma. (Phase II)
Assess the toxicity of this regimen in patients with relapsed diffuse large B cell lymphoma. (Phase II)
Assess the time to progression and duration of response in patients with relapsed diffuse large B cell lymphoma. (Phase II)

OUTLINE: This is a multicenter, phase I, dose-escalation study of CpG 7909 followed by a phase II study.

Phase I (patients with relapsed, refractory, or residual CD20+ non-Hodgkin lymphoma, closed to accrual as of 10/29/07): Patients receive rituximab IV on days 1, 8, and 15, CpG 7909 IV over 2 hours on days 6, 13, 20, and 27, and yttrium Y 90 ibritumomab tiuxetan* IV over 10 minutes on day 15 in the absence of disease progression or unacceptable toxicity. Cohorts of 6 patients receive escalating doses of CpG 7909 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. Twelve additional patients are treated at the MTD.

NOTE: *Patients receive indium In 111 ibritumomab tiuxetan IV over 10 minutes on days 1 and 8. Patients undergo whole-body gamma camera imaging, single-photon emission computed tomography/CT scans, and blood sampling after each dose of indium In 111 ibritumomab tiuxetan to determine biodistribution. If biodistribution is acceptable, patients receive yttrium Y 90 ibritumomab tiuxetan.

Phase II (patients with relapsed, refractory, or residual diffuse large B-cell lymphoma): Patients receive CPG 7909 at the MTD as determined in phase I. Patients also receive rituximab and yttrium Y 90 ibritumomab tiuxetan as in phase I.

NOTE: *Patients receive indium In 111 ibritumomab tiuxetan IV over 10 minutes on day 8. Patients undergo whole-body gamma camera imaging and blood sampling after each dose of indium In 111 ibritumomab tiuxetan to determine biodistribution.

Blood samples are collected at baseline and periodically during treatment and follow up. Samples are evaluated for immunology correlates by flow cytometry and immunoenzyme techniques and biomarkers.

After the completion of study treatment, patients are followed periodically for up to 5 years.

PROJECTED ACCRUAL: A total of 63 patients will be accrued for this study.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Histologically confirmed non-Hodgkin's lymphoma, including the following subtypes:
- Small lymphocytic lymphoma
- Lymphoplasmacytoid lymphoma
- Grade 1, 2, or 3 follicular lymphoma
- Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
- Nodal marginal zone B-cell lymphoma
- Splenic marginal zone B-cell lymphoma
- Diffuse large cell lymphoma
- Transformed lymphoma
- Mantle cell lymphoma
Recurrent, refractory, or residual disease
CD20-positive disease
Bidimensionally measurable disease (≥ 1 lesion that has a single diameter of ≥ 2 cm)
Must have < 25% bone marrow involvement of cellular marrow with lymphoma, as determined by bilateral bone marrow aspirate and biopsy
No marrow cellularity ≤ 15% (as determined on all bone marrow samples)
No prior failed stem cell collection
No CNS lymphoma
No lymphoma related to HIV or AIDS
No myelodysplastic syndromes or marrow chromosomal changes suggesting myelodysplasia

PATIENT CHARACTERISTICS:

ECOG performance status 0-2
Life expectancy ≥ 3 months
Absolute neutrophil count ≥ 1,500/mm³
Platelet count ≥ 150,000/mm³
Lymphocyte count < 5,000/mm³ (only for patients with small lymphocytic lymphoma)
Hemoglobin ≥ 8 g/dL
Total bilirubin ≤ 2 times upper limit of normal (ULN) OR direct bilirubin ≤ 1.5 times ULN
Creatinine ≤ 2 mg/dL
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No serious nonmalignant disease (e.g., active infection) or other condition that would preclude study participation
No other active primary malignancy
No known human antimouse antibodies or human antichimeric antibodies
No skin rash (e.g., Stevens-Johnson's syndrome or toxic epidermal necrolysis) after receiving rituximab
No pre-existing clinical autoimmune or antibody-mediated diseases*, including any of the following:
- Systemic lupus erythematosus
- Rheumatoid arthritis
- Multiple sclerosis
- Sjögren's syndrome
- Autoimmune thrombocytopenia
NOTE: *If no clinical symptoms, but only previously detected antibodies, then not excluded.

PRIOR CONCURRENT THERAPY:

More than 1 week since prior filgrastim (G-CSF) or sargramostim (GM-CSF) (3 weeks for pegfilgrastim)
More than 3 weeks since prior myelosuppressive chemotherapy (6 weeks for nitrosoureas or mitomycin C)
More than 4 weeks since prior major surgery, except for diagnostic surgery
More than 6 weeks since prior rituximab
No prior external-beam radiotherapy to > 25% of active bone marrow
No prior myeloablative therapies with autologous or allogeneic bone marrow transplantation or peripheral blood stem cell support
No prior radioimmunotherapy, including yttrium Y 90 ibritumomab tiuxetan, tositumomab, or iodine I 131 monoclonal antibody Lym-1
No concurrent myelosuppressive chemotherapy
No concurrent corticosteroid therapy, except prednisone (< 20 mg) for benign causes

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00438880

Locations

United States, Iowa
Holden Comprehensive Cancer Center at University of Iowa
Iowa City, Iowa, United States, 52242-1002
United States, Minnesota
Mayo Clinic Cancer Center
Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

National Cancer Institute (NCI)

Investigators

Study Chair:	Thomas E. Witzig, MD	Mayo Clinic
Investigator:	Gregory Wiseman, MD	Mayo Clinic
Investigator:	George J. Weiner, MD	Holden Comprehensive Cancer Center
Investigator:	Stephen M. Ansell, MD, PhD	Mayo Clinic
Investigator:	Joseph P. Colgan, MD	Mayo Clinic
Investigator:	Thomas M. Habermann, MD	Mayo Clinic
Investigator:	David J. Inwards, MD	Mayo Clinic
Investigator:	Patrick Johnston, MD, PhD	Mayo Clinic
Investigator:	Paul Kurtin, MD	Mayo Clinic
Investigator:	Svetomir Markovic, MD, PhD	Mayo Clinic
Investigator:	Luis F. Porrata, MD	Mayo Clinic
Investigator:	William L. White, MD	Mayo Clinic
Investigator:	Ivana Micallef, MD	Mayo Clinic

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000530062, MAYO-LS0382, MAYO-IRB-703-04
Study First Received:	February 20, 2007
Last Updated:	April 29, 2009
ClinicalTrials.gov Identifier:	NCT00438880 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

splenic marginal zone lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
recurrent small lymphocytic lymphoma
Waldenstrom macroglobulinemia

Study placed in the following topic categories:

Immunologic Factors
Lymphoma, Mantle-Cell
Lymphoma, Follicular
Lymphoma, B-Cell, Marginal Zone
Mantle Cell Lymphoma
Follicular Lymphoma
Lymphoma, B-Cell
Lymphoma, Small Cleaved-cell, Diffuse
Antibodies, Monoclonal
Leukemia, Lymphocytic, Chronic, B-Cell
Leukemia, B-cell, Chronic
Lymphoma, Large-cell
Lymphoma

Immunoglobulins
Lymphoma, Large B-Cell, Diffuse
Immunoproliferative Disorders
Rituximab
Recurrence
Lymphatic Diseases
Waldenstrom Macroglobulinemia
Chronic Lymphocytic Leukemia
Antibodies
B-cell Lymphomas
Antirheumatic Agents
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Immunologic Factors
Antineoplastic Agents
Rituximab
Physiological Effects of Drugs
Pharmacologic Actions

Antibodies, Monoclonal
Lymphatic Diseases
Neoplasms
Therapeutic Uses
Antirheumatic Agents
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Lymphoma

ClinicalTrials.gov processed this record on July 06, 2009