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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00438880
First received: February 20, 2007
Last updated: August 20, 2014
Last verified: August 2014
  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/II trial is studying the side effects and best dose of CpG 7909 when given together with rituximab and yttrium Y-90 ibritumomab tiuxetan and to see how well it works 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
Radiation: indium In 111 ibritumomab tiuxetan
Radiation: yttrium Y 90 ibritumomab tiuxetan
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: 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:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • 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. ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: No ]

    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.



Secondary Outcome Measures:
  • Progression-free Survival [ Time Frame: Up to 1 year from treatment start date ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    Duration of response (DoR) will be calculated from the documentation of response until the date of progression in the subset of patients who respond.


Enrollment: 38
Study Start Date: October 2004
Study Completion Date: June 2011
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment

Phase I patients will receive the following treatment:

  • 250 mg/m^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle
  • 5 millicurie (mCi) of (Indium-111), 1.6 mg Ibritumomab IV on day 1
  • 10 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8
  • CpG 7909 doses will be assigned in groups of 6 patients. Dose levels will escalate in each group until maximum tolerability is attained (starting at 0.08 mg/kg and sequentially escalating to 0.16 mg/kg, 0.32 mg/kg, 0.48 mg/kg). Doses will be taken day 6, 13, 20, and 27 of a 27 day cycle.
  • 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15

Phase II patients will receive the following treatment:

  • 250 mg/m^2 Rituximab IV on days 1, 8, and 15 of a 27 day cycle
  • 5 mCi (Indium-111), 1.6 mg Ibritumomab IV on day 8
  • 0.48 mg/kg CpG 7909 doses will be taken day 6, 13, 20, and 27 of a 27 day cycle.
  • 0.4 mCi/kg Yttrium-90 Zevalin IV on day 15
Biological: rituximab Drug: agatolimod sodium
Other Name: CpG 7909
Radiation: indium In 111 ibritumomab tiuxetan Radiation: yttrium Y 90 ibritumomab tiuxetan

  Show Detailed Description

  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*
    • Mantle cell lymphoma*
    • Diffuse large cell lymphoma
    • Transformed lymphoma NOTE: *Closed to accrual as of 10/29/07
  • 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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
Investigators
Study Chair: Thomas E. Witzig, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Mayo Clinic
ClinicalTrials.gov Identifier: NCT00438880     History of Changes
Other Study ID Numbers: LS0382, LS0382, 703-04, LS0382
Study First Received: February 20, 2007
Results First Received: May 20, 2014
Last Updated: August 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
recurrent adult diffuse large cell lymphoma
Waldenström macroglobulinemia
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent small lymphocytic lymphoma
recurrent mantle cell lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
recurrent marginal zone lymphoma
splenic marginal zone lymphoma

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Antibodies, Monoclonal
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 16, 2014