Safety Study of NHL With 90Y-hLL2 IgG

This study has been completed.
Sponsor:
Information provided by:
Immunomedics, Inc.
ClinicalTrials.gov Identifier:
NCT00421395
First received: January 11, 2007
Last updated: January 16, 2008
Last verified: January 2008
  Purpose

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 Intervention Phase
NHL
B-Cell NHL
Non-Hodgkins Lymphoma
Biological: 90Y-hLL2
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I/II Radioimmunotherapy of Non-Hodgkin's Lymphoma With Radiolabeled Humanized IMMU-LL2: Treatment With 90Y-hLL2 IgG

Resource links provided by NLM:


Further study details as provided by Immunomedics, Inc.:

Primary Outcome Measures:
  • Safety will be evaluated from physical examinations, hematology and chemistry testing and toxicity evaluation [ Time Frame: First 12 weeks, total 5 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Determine maximum tolerated dose (MTD) [ Time Frame: first 12 weeks ] [ Designated as safety issue: Yes ]
  • Evaluate the immunogenicity and safety of repeated infusions of 90Y-hLL2 in NHL patients. [ Time Frame: 6 weeks, 12 weeks, every 3 months if HAHA elevated ] [ Designated as safety issue: Yes ]
  • Determine the therapeutic effects, in terms of objective response rate and duration, of the therapeutic agent in NHL patients. [ Time Frame: 6 wks, 12 wks, every 3 mos for 5 years ] [ Designated as safety issue: No ]

Enrollment: 59
Study Start Date: August 2002
Study Completion Date: October 2007
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: multi
escalating in increments of 2.5 mCi/m2
Biological: 90Y-hLL2
weekly dosing for either 2 or 3 weeks
Other Names:
  • epratuzumab
  • hLL2
  • 90Y-hLL2

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00421395

Locations
France
Research Unit 463 INSERM
Nantes, Cedex, France, 44035
Service des Maladies du Sang
Lille, France, 59037
Germany
University Hospital Dresden
Dresden, Germany, 01307
Klinikum der Georg-August-Universitat Gottingen
Gottingen, Germany, 37075
Universitatsklinikum University of Saarland
Homburg/Saar, Germany, D-66421
Sponsors and Collaborators
Immunomedics, Inc.
Investigators
Study Chair: William A Wegener, MD, PhD Immunomedics, Inc.
  More Information

Additional Information:
Publications:
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 2005; 46/5:379P.
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. 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.
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.
Sharkey RM, et al. Radioimmunotherapy of non-Hodgkin's lymphoma: a critical appraisal. Expert Rev Clin Immunol 1(1) 2005:47-62.
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.
Postema EJ, et al. Dosimetric analysis of radioimmunotherapy with 186Re-epratuzumab. (Abstract No. 102) J Nucl Med Suppl 2003; 44/5:32P-33P.
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.
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
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
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.
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
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

Responsible Party: William Wegener, MD, PhD, Immunomedics, Inc.
ClinicalTrials.gov Identifier: NCT00421395     History of Changes
Other Study ID Numbers: IM-T-hLL2-06EU
Study First Received: January 11, 2007
Last Updated: January 16, 2008
Health Authority: Germany: Paul-Ehrlich-Institut
France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by Immunomedics, Inc.:
NHL
B-cell NHL
Non-Hodgkins lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on July 22, 2014