Agatolimod Sodium, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Treating Patients With Recurrent or Refractory Non-Hodgkin Lymphoma
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|ClinicalTrials.gov Identifier: NCT00438880|
Recruitment Status : Completed
First Posted : February 22, 2007
Results First Posted : September 1, 2014
Last Update Posted : February 4, 2016
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.
|Condition or disease||Intervention/treatment||Phase|
|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||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||Phase 1 Phase 2|
I. To determine the maximum tolerated dose of CpG 7909 that can be delivered in four doses (days 6, 13, 20, 27) for patients with relapsed CD20+ non-Hodgkin's lymphoma. (Phase I) II. To assess the toxicity of CpG 7909 when combined with rituximab and Y-90 Zevalin in patients with lymphoma. (Phase I) III. To assess the overall response rate (CR + PR) of this regimen in relapsed diffuse large B cell lymphoma. (Phase II) IV. To assess the toxicity of the treatment regimen in patients with relapsed diffuse large B cell lymphoma. (Phase II) V. To assess the time to progression and duration of response in patients with relapsed diffuse large B cell lymphoma. (Phase II)
I. To report the response rate (complete remission + complete remission unconfirmed + partial remission) in this patient population after CpG 7909, rituximab, and Y-90 Zevalin. (Phase I) II. To compare the biodistribution of In-111 Zevalin radioimmunoconjugate scans before and after CpG 7909. (Phase I) III. To determine the HAMA/HACA rate in patients treated with this regimen. (Phase I) IV. To determine if CpG 7909 when given in the context of rituximab and Y-90 Zevalin can stimulate immune effector cells in the blood and tumor tissue. (Phase I)
This is a dose escalation study of agatolimod sodium 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, agatolimod sodium 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 and unacceptable toxicity.
*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 agatolimod sodium at the MTD as determined in phase I. Patients 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.
After completion of study treatment, patients are followed periodically for up to 5 years.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||38 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||October 2004|
|Actual Primary Completion Date :||October 2010|
|Actual Study Completion Date :||November 2014|
Experimental: Arm I
See Detailed Description
Drug: Agatolimod Sodium
Radiation: Indium In-111 Ibritumomab Tiuxetan
Other: Laboratory Biomarker Analysis
Procedure: Radionuclide Imaging
Undergo imaging scans
Procedure: Single Photon Emission Computed Tomography
Undergo imaging scans
Radiation: Yttrium Y-90 Ibritumomab Tiuxetan
- Maximum Tolerated Dose of CpG 7909 as Determined Using the Number of Participants With a DLT at Each Dose Level [ Time Frame: at least 10 weeks post treatment up to 3 months. ]
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.
- Tumor Response [ Time Frame: Evaluations occur every three months up to a year ]
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.
- Progression-free Survival [ Time Frame: Up to 1 year from treatment start date ]The Progression-free survival (PFS) is defined as the time from registration to progression or death due to any cause. The distribution of PFS will be estimated using the method of Kaplan-Meier.
- Duration of Response [ Time Frame: Up to 1 year from treatment start date ]Duration of response (DoR) will be calculated from the documentation of response until the date of progression in the subset of patients who respond.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00438880
|United States, Iowa|
|University of Iowa/Holden Comprehensive Cancer Center|
|Iowa City, Iowa, United States, 52242|
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Thomas Witzig||Mayo Clinic|