Phase Ib Study of SC Milatuzumab in SLE

NCT ID: NCT01845740

Last Updated: 2021-08-19

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

Total Enrollment

22 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-01-31

Study Completion Date

2009-06-30

Brief Summary

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Milatuzumab will be given subcutaneously at different dose levels once (depending on the dose level) for 4 weeks to determine if milatuzumab helps to control lupus (SLE).

Detailed Description

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Milatuzumab or placebo will be given subcutaneously once weekly for 4 weeks to determine if milatuzumab helps to control lupus (SLE). The treatment portion of the study lasts 4 weeks. Then patients are followed for disease activity for at least 12 weeks. If patients respond to the study drug, they may be eligible for one course of retreatment, again followed by 12 weeks of follow-up. Patients who showed a response will continue to be followed at timepoints up to one year after treatment to assess how long the response lasts.

Conditions

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Lupus Erythematosus, Cutaneous Lupus Erythematosus, Discoid Lupus Erythematosus, Systemic Lupus Vasculitis, Central Nervous System Lupus Nephritis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Milatuzumab SC 250 mg

Milatuzumab 250 mg will be administered subcutaneously once weekly for 4 weeks.

Group Type EXPERIMENTAL

milatuzumab

Intervention Type DRUG

Milatuzumab has been used in clinical trials for multiple myeloma, non-Hodgkin's lymphoma and leukemia in the intravenous dosing form. In this study, milatuzumab is being given subcutaneously in patients with lupus.

Milatuzumab 150 mg SC

Milatuzumab 150 mg will be administered subcutaneously once weekly for 4 weeks.

Group Type EXPERIMENTAL

milatuzumab

Intervention Type DRUG

Milatuzumab has been used in clinical trials for multiple myeloma, non-Hodgkin's lymphoma and leukemia in the intravenous dosing form. In this study, milatuzumab is being given subcutaneously in patients with lupus.

Placebo SC

Placebo will be administered subcutaneously once weekly for 4 weeks.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

Placebo will be administered subcutaneously once weekly for 4 weeks.

Interventions

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milatuzumab

Milatuzumab has been used in clinical trials for multiple myeloma, non-Hodgkin's lymphoma and leukemia in the intravenous dosing form. In this study, milatuzumab is being given subcutaneously in patients with lupus.

Intervention Type DRUG

Placebo

Placebo will be administered subcutaneously once weekly for 4 weeks.

Intervention Type DRUG

Other Intervention Names

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Milatuzumab is a Cd74 targeted humanized monoclonal antibody.

Eligibility Criteria

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Inclusion Criteria

* Male or female ≥ 18 years old
* Signed written informed consent before study entry
* Diagnosis of SLE by American College of Rheumatology revised criteria (meets ≥ 4 criteria)
* Positive ANA (titer ≥ 1:80) at study entry
* At least 1 BILAG A or 2 BILAG B scores in any organ/body system and ≥ 6 SELENA-SLEDAI score
* Receiving at least 5.0 mg/day oral prednisone (or equivalent) at stable doses for at least 4 weeks prior to study entry
* If receiving immunosuppressives or antimalarial agents, at stable doses for at least 4 weeks prior to study entry

Exclusion Criteria

* Pregnant or lactating women. Women of childbearing potential must have a negative pregnancy test.
* Women of childbearing potential and fertile men not practicing or unwilling to practice birth control during the study
* Rituximab, belimumab, other prior antibody, investigational or experimental therapy within 6 months
* Allergic to murine, chimeric, humanized or human antibodies
* Hematologic abnormalities not attributed to lupus: hemoglobin \< 8.0 mg/dL, WBC \< 2000/L, ANC \< 1500/L, platelets \< 50,000/L,
* AST, ALT or alkaline phosphatase \> 3 times upper limit of normal and not attributed to lupus
* Serum creatinine \> 2.5 mg/dL, proteinuria \> 3.5 g/day
* Received live vaccine within 4 weeks
* Thrombosis, spontaneous or induced abortion, stillbirth or live birth within 4 weeks
* Antiphospholipid antibodies AND a history of thromboembolic events
* On oral anticoagulants (not including NSAIDs) within 4 weeks
* Active infection with antibiotics within 7 days
* Infection requiring hospitalization or herpes zoster treatment within 4 weeks
* Long-term infectious diseases (tuberculosis, fungal infections) active within 2 years
* Malignancy (except squamous or basal cell carcinoma, cervical CIS) within 3 years (unless approved by the medical monitor)
* History of recurrent abortions (2 or more)
* Known HIV, hepatitis B or C, other immunosuppressive states
* Other concurrent medical conditions that, in the investigator's opinion, could affect the patient's ability to tolerate or complete the study will not be eligible for the study.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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United States Department of Defense

FED

Sponsor Role collaborator

Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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William Wegener, PhD, MD

Role: PRINCIPAL_INVESTIGATOR

Gilead Sciences

Locations

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Cedars Sinai Medical Center-Wallace Rheumatic Study Center

West Hollywood, California, United States

Site Status

Countries

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United States

References

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Frolich D, Blassfeld D, Reiter K, Giesecke C, Daridon C, Mei HE, Burmester GR, Goldenberg DM, Salama A, Dorner T. The anti-CD74 humanized monoclonal antibody, milatuzumab, which targets the invariant chain of MHC II complexes, alters B-cell proliferation, migration, and adhesion molecule expression. Arthritis Res Ther. 2012 Mar 9;14(2):R54. doi: 10.1186/ar3767.

Reference Type BACKGROUND
PMID: 22404985 (View on PubMed)

Gupta P, Goldenberg DM, Rossi EA, Cardillo TM, Byrd JC, Muthusamy N, Furman RR, Chang CH. Dual-targeting immunotherapy of lymphoma: potent cytotoxicity of anti-CD20/CD74 bispecific antibodies in mantle cell and other lymphomas. Blood. 2012 Apr 19;119(16):3767-78. doi: 10.1182/blood-2011-09-381988. Epub 2012 Jan 23.

Reference Type BACKGROUND
PMID: 22271448 (View on PubMed)

Alinari L, Mahoney E, Patton J, Zhang X, Huynh L, Earl CT, Mani R, Mao Y, Yu B, Quinion C, Towns WH, Chen CS, Goldenberg DM, Blum KA, Byrd JC, Muthusamy N, Praetorius-Ibba M, Baiocchi RA. FTY720 increases CD74 expression and sensitizes mantle cell lymphoma cells to milatuzumab-mediated cell death. Blood. 2011 Dec 22;118(26):6893-903. doi: 10.1182/blood-2011-06-363879. Epub 2011 Oct 31.

Reference Type BACKGROUND
PMID: 22042694 (View on PubMed)

Santana JM, Grellier P, Rodier MH, Schrevel J, Teixeira A. Purification and characterization of a new 120 kDa alkaline proteinase of Trypanosoma cruzi. Biochem Biophys Res Commun. 1992 Sep 30;187(3):1466-73. doi: 10.1016/0006-291x(92)90467-y.

Reference Type BACKGROUND
PMID: 1417823 (View on PubMed)

Alinari L, Yu B, Christian BA, Yan F, Shin J, Lapalombella R, Hertlein E, Lustberg ME, Quinion C, Zhang X, Lozanski G, Muthusamy N, Praetorius-Ibba M, O'Connor OA, Goldenberg DM, Byrd JC, Blum KA, Baiocchi RA. Combination anti-CD74 (milatuzumab) and anti-CD20 (rituximab) monoclonal antibody therapy has in vitro and in vivo activity in mantle cell lymphoma. Blood. 2011 Apr 28;117(17):4530-41. doi: 10.1182/blood-2010-08-303354. Epub 2011 Jan 12.

Reference Type BACKGROUND
PMID: 21228331 (View on PubMed)

Hertlein E, Triantafillou G, Sass EJ, Hessler JD, Zhang X, Jarjoura D, Lucas DM, Muthusamy N, Goldenberg DM, Lee RJ, Byrd JC. Milatuzumab immunoliposomes induce cell death in CLL by promoting accumulation of CD74 on the surface of B cells. Blood. 2010 Oct 7;116(14):2554-8. doi: 10.1182/blood-2009-11-253203. Epub 2010 Jun 23.

Reference Type BACKGROUND
PMID: 20574049 (View on PubMed)

Berkova Z, Tao RH, Samaniego F. Milatuzumab - a promising new immunotherapeutic agent. Expert Opin Investig Drugs. 2010 Jan;19(1):141-9. doi: 10.1517/13543780903463854.

Reference Type BACKGROUND
PMID: 19968579 (View on PubMed)

Stein R, Smith MR, Chen S, Zalath M, Goldenberg DM. Combining milatuzumab with bortezomib, doxorubicin, or dexamethasone improves responses in multiple myeloma cell lines. Clin Cancer Res. 2009 Apr 15;15(8):2808-17. doi: 10.1158/1078-0432.CCR-08-1953. Epub 2009 Apr 7.

Reference Type BACKGROUND
PMID: 19351768 (View on PubMed)

Mark T, Martin P, Leonard JP, Niesvizky R. Milatuzumab: a promising new agent for the treatment of lymphoid malignancies. Expert Opin Investig Drugs. 2009 Jan;18(1):99-104. doi: 10.1517/13543780802636162.

Reference Type BACKGROUND
PMID: 19053886 (View on PubMed)

Stein R, Mattes MJ, Cardillo TM, Hansen HJ, Chang CH, Burton J, Govindan S, Goldenberg DM. CD74: a new candidate target for the immunotherapy of B-cell neoplasms. Clin Cancer Res. 2007 Sep 15;13(18 Pt 2):5556s-5563s. doi: 10.1158/1078-0432.CCR-07-1167.

Reference Type BACKGROUND
PMID: 17875789 (View on PubMed)

Other Identifiers

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IMMU-115-04

Identifier Type: -

Identifier Source: org_study_id

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