Clinical trial NCT00421525: Phase I/II Study of hLL1 in Multiple Myeloma
Official title: A Phase I/II Study of Immunotherapy With hLL1 Administered Twice Weekly for 4 Consecutive Weeks in Patients With Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Myeloma
Myeloma, Plasma-Cell
PLASMACYTOMA
Keywords: multiple myeloma
Myeloma, Plasma-Cell
PLASMACYTOMA
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2007-01-12
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 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.

Primary outcomes:
measure: safety and tolerability of hLL1 administered twice weekly for 4 consecutive weeks
timeFrame: first 12 weeks, then over 2 years
Secondary outcomes:
measure: The secondary objectives are to obtain information on efficacy, pharmacodynamics, pharmacokinetics, and immunogenicity, and to determine the optimal dose for subsequent studies.
timeFrame: first 12 weeks, then over 2 years
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Winship Cancer Institute, Emory University
state: Georgia
city: Goshen
country: United States
facility: Center for Cancer Care
state: Indiana
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: New York Presbyterian Hospital/Cornell Medical Center
state: New York
city: Philadelphia
country: United States
facility: Hospital University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Gilead Sciences
name: William Wegener, MD, PhD
role: STUDY_CHAIR
References:
citation: 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.
citation: 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.
citation: 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
citation: Chang CH, Sapra P, Vanama SS, Hansen HJ, Horak ID, Goldenberg DM. Effective therapy of human lymphoma xenografts with a novel recombinant ribonuclease/anti-CD74 humanized IgG4 antibody immunotoxin. Blood. 2005 Dec 15;106(13):4308-14. doi: 10.1182/blood-2005-03-1033. Epub 2005 Aug 18.
citation: 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. doi: 10.1182/blood-2004-03-0890. Epub 2004 Aug 5.
citation: 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.
citation: 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. doi: 10.1158/1078-0432.CCR-04-0182.
citation: 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.
citation: 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. doi: 10.1046/j.1365-2567.1999.00868.x.
citation: Kaufman JL, Niesvizky R, Stadtmauer EA, Chanan-Khan A, Siegel D, Horne H, Wegener WA, Goldenberg DM. Phase I, multicentre, dose-escalation trial of monotherapy with milatuzumab (humanized anti-CD74 monoclonal antibody) in relapsed or refractory multiple myeloma. Br J Haematol. 2013 Nov;163(4):478-86. doi: 10.1111/bjh.12565. Epub 2013 Sep 25.