Safety Study of NHL With 90Y-hLL2 IgG

Non-Hodgkins Lymphoma Clinical Trial

Official title:

Phase I/II Radioimmunotherapy of Non-Hodgkin's Lymphoma With Radiolabeled Humanized IMMU-LL2: Treatment With 90Y-hLL2 IgG

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00421395
• Other study ID #: IM-T-hLL2-06EU
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: August 2002
• Est. completion date: October 2007

Study information

• Verified date: January 2008
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: October 2007
• Est. primary completion date: October 2007
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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.

• Patients must be > 18 years of age

• Measurable disease by CT, with at least one lesion > 1.5 cm in one or both dimensions

• less than 25% bone marrow involvement as determined by bone marrow biopsy

• Patient must have greater than 15% cellularity of the bone marrow.

• Patients must be at least 4 weeks beyond any major surgery.

• Patients must be at least 4 weeks beyond any radiation therapy to the index lesion and must have recovered from radiation induced toxicity.

• 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

• 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.

• Patients must be able to give cognizant informed consent.

Exclusion Criteria:

• 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.

• Patients with metastasis to the brain.

• 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.

• Women who test positive for pregnancy.

• Patients with splenomegaly.

• Patients with > 4 treatment regimens prior to this protocol, including chemotherapy, radiotherapy and/or other immunotherapy.

• Patients with prior radioimmunotherapy treatments (unless for retreatment under this protocol).

• Patients receiving rituximab within 3 months, unless progressing after treatment.

• Patients with <50% LVEF by required MUGA or 2-D ECHO.

• Patients with <60% of predicted value by required pulmonary function tests.

• Patients who have active Hepatitis B or C or are known HIV positive.

• Patients with another primary malignancy (except basal/squamous cell carcinoma of the skin or carcinoma in-situ of the cervix.

• 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.

Related Conditions & MeSH terms

• B-cell NHL
• Lymphoma
• Lymphoma, Non-Hodgkin
• NHL
• Non-Hodgkins Lymphoma

Intervention

Biological:
• 90Y-hLL2
weekly dosing for either 2 or 3 weeks

Locations

Country	Name	City	State
France	Service des Maladies du Sang	Lille
France	Research Unit 463 INSERM	Nantes	Cedex
Germany	University Hospital Dresden	Dresden
Germany	Klinikum der Georg-August-Universitat Gottingen	Gottingen
Germany	Universitatsklinikum University of Saarland	Homburg/Saar

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

France,  Germany, 

References & Publications (21)

Bodet-Milin C, et al. FDG-PET predicts response to fractionated radioimmunotherapy with 90Y-epratuzumab anti-CD22 MAb in patients with NHL. (Abstract #4782) Blood 2995; 106/11:275b.

Bodet-Milin C, et al. Positron emission tomography with F-18-fluorodeoxyglucose (PET-FDG) predicts response to fractionated radioimmunotherapy (RIT) using 90Y-epratuzumab in non-Hodgkin's lymphoma (NHL). (Abstract #1234) J Nucl Med Abstract Bk Suppl 2 200

Chatal J-F, et al. Fractionated radioimmunotherapy in NHL with DOTA-conjugated humanized anti-CD22 epratuzumab at high cumulative 90Y doses. (Abstract #447) J Nucl Med Abstract Bk Suppl 2 2005; 46/5:155P.

Chatal J-F, et al. Fractionated-dose radioimmunotherapy in non-Hodgkin's lymphoma (NHL) using DOTA-conjugated, 90Y-radiolabeled, humanized anti-CD22 monoclonal antibody (epratuzumab). Interim results. (Abstract No. 1482) Blood 2003; 102/11:408a.

Chatal J-F, et al. Radioimmunotherapy in non-Hodgkin's lymphoma (NHL) using a fractionated schedule of DOTA-conjugated, 90Y-radiolabeled, humanized anti-CD22 monoclonal antibody, epratuzumab. (Abstract #2545) Proceedings of ASCO 2004; 23:174.

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 21 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety will be evaluated from physical examinations, hematology and chemistry testing and toxicity evaluation		First 12 weeks, total 5 years
Secondary	Determine maximum tolerated dose (MTD)		first 12 weeks
Secondary	Evaluate the immunogenicity and safety of repeated infusions of 90Y-hLL2 in NHL patients.		6 weeks, 12 weeks, every 3 months if HAHA elevated
Secondary	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

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