Safety Study of NHL With 90Y-hLL2 IgG
Study Details
Study Description
Brief Summary
This will be an open label, multiple center, non-randomized, dose-escalation Phase I/II trial, designed to evaluate the safety and effectiveness of a repeated, outpatient regimen utilizing IMMU-hLL2 intact monoclonal antibody IgG labeled with different doses of 90Y for the treatment of patients B-cell lymphoma (NHL).
Condition or Disease | Intervention/Treatment | Phase |
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Phase 1/Phase 2 |
Detailed Description
90Y-labeled hLL2 will be administered according to a schedule based upon whether or not a patient had prior high-dose chemotherapy with a marrow or stem cell transplant. Patients with both indolent and aggressive types of NHL will be enrolled at each dose level without segregation. However, at the conclusion of the trial, with the maximum tolerated dose (MTD) defined, a minimum number of 6 patients with indolent NHL, 6 patients with aggressive NHL, and 6 patients with >25% bone marrow involvement will be studied at that dose level.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
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Experimental: multi escalating in increments of 2.5 mCi/m2 |
Biological: 90Y-hLL2
weekly dosing for either 2 or 3 weeks
Other Names:
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Outcome Measures
Primary Outcome Measures
- Safety will be evaluated from physical examinations, hematology and chemistry testing and toxicity evaluation [First 12 weeks, total 5 years]
Secondary Outcome Measures
- Determine maximum tolerated dose (MTD) [first 12 weeks]
- Evaluate the immunogenicity and safety of repeated infusions of 90Y-hLL2 in NHL patients. [6 weeks, 12 weeks, every 3 months if HAHA elevated]
- Determine the therapeutic effects, in terms of objective response rate and duration, of the therapeutic agent in NHL patients. [6 wks, 12 wks, every 3 mos for 5 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
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All patients must have a histologic or cytological diagnosis of B-cell lymphoma, and have failed at least one regimen of standard chemotherapy. All histologic grades of non-Hodgkin's lymphoma (NHL) will be eligible for these studies.
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Patients must be > 18 years of age
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Measurable disease by CT, with at least one lesion > 1.5 cm in one or both dimensions
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less than 25% bone marrow involvement as determined by bone marrow biopsy
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Patient must have greater than 15% cellularity of the bone marrow.
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Patients must be at least 4 weeks beyond any major surgery.
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Patients must be at least 4 weeks beyond any radiation therapy to the index lesion and must have recovered from radiation induced toxicity.
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Patients must be at least 4 weeks beyond prior chemotherapy and/or immunotherapy, or 2-weeks after corticosteroids, and their blood counts must be within the eligibility criteria. Corticosteroids may, however, be given concomitantly if used to treat adrenal insufficiency
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Patients must have a performance status of 70 or greater on the Karnofsky scale equivalent to ECOG 0-1 (See Appendix A) and a minimal life expectancy of 6 months.
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Patients must be able to give cognizant informed consent.
Exclusion Criteria:
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Patients with a significant concurrent medical complication including severe anorexia, nausea or vomiting that in the judgement of the Investigator could affect the patient's ability to tolerate or complete this study.
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Patients with metastasis to the brain.
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Patients with extensive irradiation to more than 25% of their red marrow will be excluded, except those who had total body irradiation in the context of bone marrow or stem cell transplantation regimen with subsequent engraftment of a functional marrow (i.e., resulting in normal peripheral blood counts). Subjects who have received external radiation to specific organs or areas at the maximum tolerated level are also excluded.
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Women who test positive for pregnancy.
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Patients with splenomegaly.
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Patients with > 4 treatment regimens prior to this protocol, including chemotherapy, radiotherapy and/or other immunotherapy.
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Patients with prior radioimmunotherapy treatments (unless for retreatment under this protocol).
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Patients receiving rituximab within 3 months, unless progressing after treatment.
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Patients with <50% LVEF by required MUGA or 2-D ECHO.
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Patients with <60% of predicted value by required pulmonary function tests.
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Patients who have active Hepatitis B or C or are known HIV positive.
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Patients with another primary malignancy (except basal/squamous cell carcinoma of the skin or carcinoma in-situ of the cervix.
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Patients with other serious medical, surgical, or psychiatric history, unless currently stable and well controlled, without significant increase in treatment medications for at least 30 days preceding study entry.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
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1 | Research Unit 463 INSERM | Nantes | Cedex | France | 44035 |
2 | Service des Maladies du Sang | Lille | France | 59037 | |
3 | University Hospital Dresden | Dresden | Germany | 01307 | |
4 | Klinikum der Georg-August-Universitat Gottingen | Gottingen | Germany | 37075 | |
5 | Universitatsklinikum University of Saarland | Homburg/Saar | Germany | D-66421 |
Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Chair: William A Wegener, MD, PhD, Gilead Sciences
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Goldenberg DM. The role of radiolabeled antibodies in the treatment of non-Hodgkin's lymphoma: the coming of age of radioimmunotherapy. Crit Rev Oncol Hematol. 2001 Jul-Aug;39(1-2):195-201. Review.
- Griffiths GL, Govindan SV, Sharkey RM, Fisher DR, Goldenberg DM. 90Y-DOTA-hLL2: an agent for radioimmunotherapy of non-Hodgkin's lymphoma. J Nucl Med. 2003 Jan;44(1):77-84.
- Hajjar G. et al. Phase I/II radioimmunotherapy trial with 90Y-labeled epratuzumab (LymphoCide; anti-CD22 monoclonal antibody) in relapsed/refractory non-Hodgkin's lymphoma (NHL). (Abstract #583) J Nucl Med Suppl, May 2001; 42/5: 156P.
- Hindorf C, Lindén O, Stenberg L, Tennvall J, Strand SE. Change in tumor-absorbed dose due to decrease in mass during fractionated radioimmunotherapy in lymphoma patients. Clin Cancer Res. 2003 Sep 1;9(10 Pt 2):4003S-6S.
- Juweid M, Schuster SL, et al. Updated results of radioimmunotherapy of relapsed/refractory non-Hodgkin's lymphoma with conventional and stem cell supported doses of 90Y-labeled humanized LL2 anti-CD22 monoclonal antibody. (Abstract #40) Cancer Biother & Radiopharm 2000, 15/4: 408
- Leonard JP, Siegel JA, Goldsmith SJ. Comparative physical and pharmacologic characteristics of iodine-131 and yttrium-90: implications for radioimmunotherapy for patients with non-Hodgkin's lymphoma. Cancer Invest. 2003 Apr;21(2):241-52. Review.
- Lindén O, et al. Durable response to 90-yttrium-epratuzumab (hLL2) in B-cell lymphoma failing chemotherapy by using dose-fractionation schedule. (Abstract presented at the American Society of Hematology 43rd Annual Meeting) Blood 2001; 98/11: 602a
- Lindén O, et al. Outcome and absorbed dose following 90-yttrium-epratuzumab in B-cell lymphoma, using a dose-fractionation schedule. (Abstract No. 1479) Blood 2003; 102/11:407a.
- Lindén O, et al. Radioimmunotherapy with Y-90-Epratuzumab in patients with previously treated B-cell lymphoma. A fractionated dose-escalation study. (Abstract 5.05 Hematology) Special Issue: World Congress of Nuclear Medicine, September 2002; 5/17.
- Lindén O, Hindorf C, Cavallin-Ståhl E, Wegener WA, Goldenberg DM, Horne H, Ohlsson T, Stenberg L, Strand SE, Tennvall J. Dose-fractionated radioimmunotherapy in non-Hodgkin's lymphoma using DOTA-conjugated, 90Y-radiolabeled, humanized anti-CD22 monoclonal antibody, epratuzumab. Clin Cancer Res. 2005 Jul 15;11(14):5215-22.
- Lindén O, Tennvall J, Cavallin-Ståhl E, Darte L, Garkavij M, Lindner KJ, Ljungberg M, Ohlsson T, Sjögreen K, Wingårdh K, Strand SE. Radioimmunotherapy using 131I-labeled anti-CD22 monoclonal antibody (LL2) in patients with previously treated B-cell lymphomas. Clin Cancer Res. 1999 Oct;5(10 Suppl):3287s-3291s.
- Lindén O, Tennvall J, et al. A Phase I/II trial with Y-90 hLL2 in recurrent B-cell lymphomas. Preliminary results. (Abstract #67) Cancer Biother & Radiopharm 2000, 15/4: 413
- Liu, Huaitian, et al. Targeting the CD22 receptor with RNA damaging agents. Cancer Drug Discovery and Development: Tumor Targeting in Cancer Therapy. Edited by: M Pagé, Humana Press Inc., Totowa, NJ: 109-118
- Postema EJ, et al. Dosimetric analysis of radioimmunotherapy with 186Re-epratuzumab. (Abstract No. 102) J Nucl Med Suppl 2003; 44/5:32P-33P.
- Sharkey RM, Brenner A, Burton J, Hajjar G, Toder SP, Alavi A, Matthies A, Tsai DE, Schuster SJ, Stadtmauer EA, Czuczman MS, Lamonica D, Kraeber-Bodere F, Mahe B, Chatal JF, Rogatko A, Mardirrosian G, Goldenberg DM. Radioimmunotherapy of non-Hodgkin's lymphoma with 90Y-DOTA humanized anti-CD22 IgG (90Y-Epratuzumab): do tumor targeting and dosimetry predict therapeutic response? J Nucl Med. 2003 Dec;44(12):2000-18.
- Sharkey RM, Burton J, Goldenberg DM. Radioimmunotherapy of non-Hodgkin's lymphoma: a critical appraisal. Expert Rev Clin Immunol. 2005 May;1(1):47-62. doi: 10.1586/1744666X.1.1.47.
- IM-T-hLL2-06EU