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Phase I/II Study of CpG 7909, Rituximab, and Yttrium Y 90 Ibritumomab Tiuxetan in Patients With CD20+ Recurrent or Refractory Non-Hodgkin's Lymphoma
Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Trial Contact Information
Registry Information
Alternate Title
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
Basic Trial Information
| Phase | Type | Status | Age | Protocol IDs |
|---|
| Phase II, Phase I | Biomarker/Laboratory analysis, Diagnostic, Treatment | Closed | 18 and over | MAYO-LS0382
MAYO-IRB-703-04, NCT00438880 |
Special Category:
SPORE trial 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)
Entry 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
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
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.]
Expected Enrollment 63A total of 63 patients will be accrued for this study. Outcomes Primary Outcome(s)Toxicity
Immunostimulation (optimal immunological dose)
Change in fraction of injected activity
Tumor response
Secondary Outcome(s)Response rate (complete response [CR], CR unconfirmed, partial response)
Human antimouse antibodies and human antichimeric antibodies
Event-free survival
Overall survival
Progression-free survival
Duration of response
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.
Trial Contact Information
Trial Lead Organizations Mayo Clinic Cancer Center | | | | Thomas Witzig, MD, Protocol chair | | | | | Gregory Wiseman, MD, Protocol co-chair | | | | | George Weiner, MD, Protocol co-chair | | | | | Stephen Ansell, MD, PhD, Protocol co-chair | | | | | Joseph Colgan, MD, Protocol co-chair | | | | | Thomas Habermann, MD, Protocol co-chair | | | | | David Inwards, MD, Protocol co-chair | | | | | Patrick Johnston, MD, PhD, Protocol co-chair | | | | | Paul Kurtin, MD, Protocol co-chair | | | | | Svetomir Markovic, MD, PhD, Protocol co-chair | | | | | Luis Porrata, MD, Protocol co-chair | | | | | William White, MD, Protocol co-chair | | | | | Ivana Micallef, MD, Protocol co-chair | | | |
| Registry Information | | | 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 | | | Trial Start Date | | 2004-10-20 | | | Trial Completion Date | | 2007-11-16 (estimated) | | | Registered in ClinicalTrials.gov | | NCT00438880 | | | Date Submitted to PDQ | | 2007-01-04 | | | Information Last Verified | | 2009-03-23 | | | NCI Grant/Contract Number | | CA097274, CA15083 |
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. |
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