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Phase I/II Study of hLL1 in Multiple Myeloma
This study is currently recruiting participants.
Verified by Immunomedics, Inc., August 2008
Sponsored by: Immunomedics, Inc.
Information provided by: Immunomedics, Inc.
ClinicalTrials.gov Identifier: NCT00421525
  Purpose

This is a Phase I/II, open-label, multi-center study conducted in patients with recurrent or refractory multiple myeloma who have failed at least two prior standard systemic treatments.


Condition Intervention Phase
Multiple Myeloma
Myeloma, Plasma-Cell
Plasmacytoma
Biological: milatuzumab
Phase I
Phase II

Genetics Home Reference related topics: aceruloplasminemia hemophilia
MedlinePlus related topics: Cancer Multiple Myeloma
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Safety/Efficacy Study
Official Title: A Phase I/II Study of Immunotherapy With hLL1 Administered Twice Weekly for 4 Consecutive Weeks in Patients With Multiple Myeloma

Further study details as provided by Immunomedics, Inc.:

Primary Outcome Measures:
  • safety and tolerability of hLL1 administered twice weekly for 4 consecutive weeks [ Time Frame: first 12 weeks, then over 2 years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • The secondary objectives are to obtain information on efficacy, pharmacodynamics, pharmacokinetics, and immunogenicity, and to determine the optimal dose for subsequent studies. [ Time Frame: first 12 weeks, then over 2 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 66
Study Start Date: January 2007
Arms Assigned Interventions
Multiple Doses: Active Comparator
Multiple Dose levels
Biological: milatuzumab
twice weekly dosing for 4 weeks, total of 8 doses

Detailed Description:

All patients receive hLL1 administered intravenously twice weekly for 4 consecutive weeks. Cohorts of 3-6 patients will receive escalating doses of hLL1 in order to determine the maximum tolerated dose (MTD) for this administration schedule. Up to approximately 30 additional patients will be entered at one or more dose levels at or below the MTD in order to determine the optimal dose for subsequent studies.

  Eligibility

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

Inclusion Criteria:

  • Able to provide signed, informed consent;
  • Male or female, >/=18 years old;
  • Meets clinical trial criteria for a diagnosis of multiple myeloma (Appendix 1)
  • Stage II or III at study entry by Durie-Salmon staging, with either renal function subclassification (A or B) allowed (Appendix 2).
  • Secretory multiple myeloma one or more criteria for measurable disease (serum M protein >1.0 gm/dl measured by serum protein electrophoresis, serum free light chain measurement >200 mg/dl, urinary M protein excretion >200 mg/24 hours);
  • Refractory or relapsed to at least two prior standard systemic anti-myeloma treatment regimens;
  • Adequate performance status (Karnofsky Scale >/= 60%);
  • Life expectancy at least 6 months;
  • Adequate hematologic status within 2 weeks before study drug administration:
  • Hemoglobin >8.0 g/dL and platelets > 50,000/mm3 (both without transfusion or other hematologic support within 7 days of laboratory testing)
  • White blood count (WBC) > 2,000/mm3and absolute neutrophil count (ANC) >1,000/mm3 (both without the use of colony stimulating factors within 7 days of laboratory testing)
  • Adequate renal function: serum creatinine < 1.5 x the upper limit of normal (ULN);
  • Adequate hepatic function AST or ALT < 2.5 x the ULN; Total bilirubin < 1.5 x the ULN

Exclusion Criteria:

  • Pregnant or lactating women.
  • Women of childbearing potential and fertile men who are not practicing or who are unwilling to practice birth control while enrolled in the study until at least 12 weeks after the last hLL1 infusion;
  • Prior chemotherapy, immunotherapy, radiotherapy, plasmapheresis, kyphoplasty, or major surgery within 4 weeks; prior stem cell transplant within 12 weeks; prior treatment with rituximab within 6 months. Must have recovered from all toxicity from prior treatments;
  • Prior therapy with other murine, chimeric, human or humanized monoclonal antibodies, unless HAHA tested and negative;
  • Prior treatment with any investigational agents within 3 months, unless completed follow-up, off study, and agreed by Sponsor;
  • Prior malignancy within 5 years, excluding multiple myeloma, non-melanoma skins cancers and cervical carcinoma in situ;
  • Known to be HIV positive, or hepatitis B or C positive;
  • Known autoimmune disease or presence of autoimmune phenomena;
  • Systemic infection or requiring anti-infectives within 7 days before first dose of study drug;
  • Substance abuse or other concurrent medical conditions that, in the investigator's opinion, could confound study interpretation or affect the patient's ability to tolerate or complete the study.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00421525

Contacts
Contact: Dennis Simpson, RN 973-605-8200 dsimpson@immunomedics.com
Contact: Heather Horne 973-727-7589 hhorne@immunomedics.com

Locations
United States, Georgia
Winship Cancer Institute, Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Dennis Simpson, RN     973-605-8200        
Principal Investigator: Jonathan Kaufman, MD            
United States, Indiana
Center for Cancer Care Recruiting
Goshen, Indiana, United States, 46526
Contact: Susan Garl, RN     574-535-2974        
Principal Investigator: Daniel Bruetman, MD            
United States, New Jersey
Hackensack University Medical Center Recruiting
Hackensack, New Jersey, United States, 07601
Contact: Dennis Simpson     973-605-8200        
Principal Investigator: David Siegel, MD            
United States, New York
New York Presbyterian Hospital/Cornell Medical Center Recruiting
New York, New York, United States, 10021
Contact: Jessica Coyne     212-746-1540        
Principal Investigator: Ruben Niesvizky, MD            
Roswell Park Cancer Institute Recruiting
Buffalo, New York, United States, 14263
Contact: Dennis Simpson     973-605-8200        
Principal Investigator: Asher Chanan-Khan, MD            
United States, Pennsylvania
Hospital University of Pennsylvania Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Dennis Simpson, RN     973-605-8200        
Principal Investigator: Edward Stadtmauer, MD            
Sponsors and Collaborators
Immunomedics, Inc.
Investigators
Study Chair: William Wegener, MD, PhD Immunomedics, Inc.
  More Information

Related Info  This link exits the ClinicalTrials.gov site

Publications:
Sapra P, et al. In vitro and in vivo targeting and therapy of an antibody-drug conjugate (IMMU-110) in B-cell malignancies. (Abstract #3287) Blood 2004; 104/11:898a.
Stein R, et al. Therapeutic activity of a new antibody-drug immunoconjugate, IMMU-110, in preclinical studies targeted against multiple myeloma. (Abstract #6535) Proceedings of ASCO 2004; 23:564.
Griffiths GL, et al. Promising therapeutic activity of a new drug immunoconjugate, IMMU-110, in a human Burkitt lymphoma model. (Abstract #2381) Blood 2003; 102/11:645a
Sapra P, et al. Preclinical safety and efficacy of two novel immunotoxins consisting of Ranpirnase (Rap) fused to an internalizing anti-CD74 humanized IgG4 antibody in human non-Hodgkin's lymphoma xenografts. (Abstract #346) Blood 2005; 106/11:105a
Stein R, Qu Z, Cardillo TM, Chen S, Rosario A, Horak ID, Hansen HJ, Goldenberg DM. Antiproliferative activity of a humanized anti-CD74 monoclonal antibody, hLL1, on B-cell malignancies. Blood. 2004 Dec 1;104(12):3705-11. Epub 2004 Aug 5.
Vanama SS, et al. Construction and characterization of a novel ribonuclease immunotoxin consisting of two Ranpirnase (Rap) molecules fused to an internalizing anti-CD74 humanized IgG4 antibody. (Abstract #3289) Blood 2004; 104/11:899a.
Burton JD, Ely S, Reddy PK, Stein R, Gold DV, Cardillo TM, Goldenberg DM. CD74 is expressed by multiple myeloma and is a promising target for therapy. Clin Cancer Res. 2004 Oct 1;10(19):6606-11.
Griffiths GL, Mattes MJ, Stein R, Govindan SV, Horak ID, Hansen HJ, Goldenberg DM. Cure of SCID mice bearing human B-lymphoma xenografts by an anti-CD74 antibody-anthracycline drug conjugate. Clin Cancer Res. 2003 Dec 15;9(17):6567-71.
Stein R, et al. Preclinical evaluation of a humanized anti-CD74 monoclonal antibody, hLL1, for treatment of B-cell malignancies. (Abstract #630) Blood 2003; 102/11: 181a
Ong GL, Goldenberg DM, Hansen HJ, Mattes MJ. Cell surface expression and metabolism of major histocompatibility complex class II invariant chain (CD74) by diverse cell lines. Immunology. 1999 Oct;98(2):296-302.

Responsible Party: Immunomedics, Inc. ( William Wegener )
Study ID Numbers: PROTOCOL: IMMU-115-01
Study First Received: January 11, 2007
Last Updated: August 1, 2008
ClinicalTrials.gov Identifier: NCT00421525  
Health Authority: United States: Food and Drug Administration

Keywords provided by Immunomedics, Inc.:
multiple myeloma
Myeloma, Plasma-Cell
PLASMACYTOMA

Study placed in the following topic categories:
Immunoproliferative Disorders
Blood Protein Disorders
Hematologic Diseases
Blood Coagulation Disorders
Vascular Diseases
Paraproteinemias
Hemostatic Disorders
Multiple Myeloma
Hemorrhagic Disorders
Multiple myeloma
Plasmacytoma
Plasmacytoma anaplastic
Lymphoproliferative Disorders
Neoplasms, Plasma Cell

Additional relevant MeSH terms:
Neoplasms
Neoplasms by Histologic Type
Immune System Diseases
Cardiovascular Diseases

ClinicalTrials.gov processed this record on January 14, 2009