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Adult Non-Hodgkin LymphomaPhase 1/2NCT00438880

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

A Phase 1/2 study testing Agatolimod Sodium, Indium In-111 Ibritumomab Tiuxetan and Laboratory Biomarker Analysis in people with Adult Non-Hodgkin Lymphoma and Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, run by Mayo Clinic at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Agatolimod Sodium, Indium In-111 Ibritumomab Tiuxetan and Laboratory Biomarker Analysis
Could I receive a placebo?
No, everyone receives an active treatment
How many people
38 participants
Where
2 sitesUnited States
Study dates
Oct 2004to Nov 2014
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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)

Who cannot join

  • 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
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  • 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)
  • Myelosuppressive chemotherapy =< 3 weeks prior to study registration (=< 6 weeks if rituximab, nitrosourea, or Mitomycin C)
  • 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
  • Abnormal renal function (serum creatinine > 2 mg/dL)
  • 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)
  • Received prior external beam radiation therapy to > 25% of active bone marrow
  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • University of Iowa/Holden Comprehensive Cancer Center

    Iowa City, Iowa, 52242

  • Mayo Clinic

    Rochester, Minnesota, 55905

Other trials in United States

About this study

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

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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)

SECONDARY OBJECTIVES:

  1. 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)

OUTLINE:

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.

Being tested
Agatolimod Sodium, Indium In-111 Ibritumomab Tiuxetan, Laboratory Biomarker Analysis, Radionuclide Imaging, Rituximab
Medical subject headings
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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Agatolimod SodiumDrug

    Also called (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

    Given IV

  • Indium In-111 Ibritumomab TiuxetanRadiation

    Also called IDEC In2B8, IDEC-In2B8, In 111 Ibritumomab Tiuxetan, In 111 Zevalin

    Given IV

  • Laboratory Biomarker AnalysisOther

    Correlative study

  • Radionuclide ImagingProcedure or surgery

    Also called nuclear medicine scan, radioimaging, Radionuclide Scanning, Scan

    Undergo imaging scans

  • RituximabBiological

    Also called BI 695500, C2B8 Monoclonal Antibody, Chimeric Anti-CD20 Antibody, IDEC-102

    Given IV

  • Single Photon Emission Computed TomographyProcedure or surgery

    Also called Medical Imaging, Single Photon Emission Computed Tomography, Single Photon Emission Tomography, single-photon emission computed tomography, SPECT

    Undergo imaging scans

  • Yttrium Y-90 Ibritumomab TiuxetanRadiation

    Also called IDEC-Y2B8, IDEC-Y2B8 monoclonal antibody, Y 90 Ibritumomab Tiuxetan, Y 90 Zevalin

    Given IV

Study groups in NCT00438880
Study groupRoleWhat they receive
Arm IExperimentalSee Detailed Description
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: at least 10 weeks post treatment up to 3 months.

  2. 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.

    Measured: Evaluations occur every three months up to a year

Secondary outcomes (2)

  1. Progression-free Survival

    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.

    Measured: Up to 1 year from treatment start date

  2. Duration of Response

    Duration of response (DoR) will be calculated from the documentation of response until the date of progression in the subset of patients who respond.

    Measured: Up to 1 year from treatment start date

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Feb 2007 (estimated)
  2. Study startOct 2004
  3. Primary completionOct 2010
  4. Study completionNov 2014

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00438880
Sponsor's protocol ID
LS0382
Other IDs
NCI-2009-01275, LS0382, P30CA015083
Status last verified
Sep 2015
First submitted
20 Feb 2007
Last updated
4 Feb 2016
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Agatolimod Sodium, Indium In-111 Ibritumomab Tiuxetan and Laboratory Biomarker Analysis in people with Adult Non-Hodgkin Lymphoma and Extranodal Marginal Zone Lymphoma of Mucosa-Associated Lymphoid Tissue, run by Mayo Clinic at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Feb 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00438880.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2016.

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