Phase I/II Study of hLL1 in Multiple Myeloma

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Immunomedics, Inc.
ClinicalTrials.gov Identifier:
NCT00421525
First received: January 11, 2007
Last updated: October 3, 2012
Last verified: October 2012
  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 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of Immunotherapy With hLL1 Administered Twice Weekly for 4 Consecutive Weeks in Patients With Multiple Myeloma

Resource links provided by NLM:


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 ]

Enrollment: 25
Study Start Date: January 2007
Primary Completion Date: August 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Multiple Doses
Multiple Dose levels
Biological: milatuzumab
twice weekly dosing for 4 weeks, total of 8 doses
Other Names:
  • milatuzumab
  • CD74
  • humanized CD74
  • IMMU-115

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
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: NCT00421525

Locations
United States, Georgia
Winship Cancer Institute, Emory University
Atlanta, Georgia, United States, 30322
United States, Indiana
Center for Cancer Care
Goshen, Indiana, United States, 46526
United States, New Jersey
Hackensack University Medical Center
Hackensack, New Jersey, United States, 07601
United States, New York
Roswell Park Cancer Institute
Buffalo, New York, United States, 14263
New York Presbyterian Hospital/Cornell Medical Center
New York, New York, United States, 10021
United States, Pennsylvania
Hospital University of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Sponsors and Collaborators
Immunomedics, Inc.
Investigators
Study Chair: William Wegener, MD, PhD Immunomedics, Inc.
  More Information

Additional Information:
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
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.
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

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Immunomedics, Inc.
ClinicalTrials.gov Identifier: NCT00421525     History of Changes
Other Study ID Numbers: PROTOCOL: IMMU-115-01
Study First Received: January 11, 2007
Last Updated: October 3, 2012
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Plasmacytoma
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases

ClinicalTrials.gov processed this record on August 01, 2014