Phase I/II Study of hLL1 in Multiple Myeloma

NCT ID: NCT00421525

Last Updated: 2021-08-16

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

25 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-01-31

Study Completion Date

2009-06-30

Brief Summary

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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

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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.

Conditions

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Multiple Myeloma Myeloma, Plasma-Cell PLASMACYTOMA

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Multiple Doses

Multiple Dose levels

Group Type OTHER

milatuzumab

Intervention Type BIOLOGICAL

twice weekly dosing for 4 weeks, total of 8 doses

Interventions

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milatuzumab

twice weekly dosing for 4 weeks, total of 8 doses

Intervention Type BIOLOGICAL

Other Intervention Names

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CD74 humanized CD74 IMMU-115 hLL1

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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William Wegener, MD, PhD

Role: STUDY_CHAIR

Gilead Sciences

Locations

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Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

Site Status

Center for Cancer Care

Goshen, Indiana, United States

Site Status

Hackensack University Medical Center

Hackensack, New Jersey, United States

Site Status

Roswell Park Cancer Institute

Buffalo, New York, United States

Site Status

New York Presbyterian Hospital/Cornell Medical Center

New York, New York, United States

Site Status

Hospital University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND

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.

Reference Type BACKGROUND

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

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 16109781 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15297317 (View on PubMed)

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.

Reference Type BACKGROUND

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.

Reference Type BACKGROUND
PMID: 15475450 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14695162 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 10540230 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24112026 (View on PubMed)

Related Links

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Other Identifiers

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PROTOCOL: IMMU-115-01

Identifier Type: -

Identifier Source: org_study_id

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