Neoplasms

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Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

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Paraproteinemias

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All Drugs and Chemicals

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Doxorubicin

Liposomal doxorubicin

Immunoglobulins

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Antibiotics, Antitubercular

Enzyme Inhibitors

4 Different dose levels of hLL1-DOX will be studied in groups of 3-6 patients. Once an optimal dose has been found, up to additional 30 patients will be studied at that dose level.

hLL1-DOX will be administered intravenously (through a vein) on days 1, 4, 8 \& 11 every 21 days for up to 8 treatment cycles. 4 different dose levels of hLL1-DOX will be studied for safety and tolerability.

hLL1-DOX (the doxorubicin conjugate of milatuzumab)

This study is a Ph I trial to test the safety of the study drug, hLL1-DOX at different dose levels in patients with recurrent multiple myeloma. HLL1 is also known as milatuzumab and is attached to doxorubicin in this clinical trial.

In this clinical research trial, hLL1-DOX will be administered on days 1, 4, 8 and 11. This treatment cycle will be repeated every 3 weeks as long as patients continue to tolerate it, for a maximum of 8 treatment cycles (approximately 6 months).

A Study of hLL1-DOX (Milatuzumab-Doxorubicin Antibody-Drug Conjugate) in Patients With Multiple Myeloma

A Phase I/II Study of hLL1-DOX (Milatuzumab-Doxorubicin Antibody-Drug Conjugate) in Patients With Multiple Myeloma

The frequency and severity of adverse events (AEs) will be tabulated by MedDRA Preferred Term and System Organ Class (SOC) for each dose group. AEs will be classified using the MedDRA version 8.0 with severity assessed by NCI CTC v3 toxicity grades

All patients who were treated with at least one complete dose of study drug and have available response assessment data will constitute the efficacy population. For efficacy evaluations, treatment responses based on IMWG Response Criteria, response duration and progression-free survival will be tabulated and summarized by descriptive statistics for patients in each dose group.

Gilead Sciences

Bevacizumab

Bortezomib

Immunoglobulins, Intravenous

Myeloma Proteins

Paraproteins

Immunoglobulin M

Immunoglobulin A

Bortezomib will be administered at 1.3 mglm2 IVP on Days 1. 4, 8, and 11. Response will be assessed subsequent to each cycle. A total of 8 cycles would beplanned. Patients would be removed subsequent to Cycle 2. if progression of disease is documented.

David S Siegel, MD, PhD

The purpose of this study is to determine whether the combination of bevacizumab and bortezomib have increased efficacy in the treatment of relapsed/ refractory multiple myeloma.

Rationale: With the identification of thalidomide as an active agent in Multiple Myeloma, the role of angiogenesis in its pathogenesis has become a subject of much investigation. Micro vessel density (neovascularization) is inversely related to prognosis in Multiple Myeloma. Response to thalidomide was felt to correlate with a decline in microvessel density (Singhal et al NEJM). While the mechanism of neovascularization is yet to be fully elucidated, a number of models have shown VEGF to play a central role.

Thalidomide has been shown to synergize with a number of agents used to treat MM, including bortezomib. (Wang et al ASH 2005) This would justify the use of other therapeutics with known antiangiogenic activity in conjunction with established antimyeloma therapies.

Bortezomib, which has the precedence of known synergy with Thalidomide and has an extremely well established optimal dose, schedule, response rate, event free survival, and overall survival would make it an excellent candidate for combination therapy with other established antiangiogenic compounds.

There have been several reports of the role of VEGF in multiple myeloma. It has been shown that multiple myeloma cells secreteVEGF, which further promotes production of IL-6 in BMSCs, as well as migration and proliferation of the tumor cells. Thus VEGF is both an autocrine growth factor and trigger of IL-6-mediated paracrine multiple myeloma cell growth. Recent reports have highlighted the major role of VEGF in multiple myeloma pathogenesis, demonstrating the VEGF also increases microvessel density in the bone marrow. VEGF also inhibits dendritic cells. Taken together, these preclinical reports make strong suggestion for the promise of VEGF targeted agents in multiple myeloma (Le Gouill et al 2004).

A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma

A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed Refractory Multiple Myeloma

Study Schema: Bortezomib will be administered on Days 1. 4, 8, and 11. Response will be assessed subsequent to each 21-day cycle. Progression is defined using the Bladé criteria, defined progression as an increase of \>25% in paraprotein or urinary light chain excretion (or marrow plasma cell percentage in the marrow

The secondary objective of this study is to assess the safely and tolerability of the combination treatment of bevacizumnab and bortezomnib. Adjustments in the dosing schedule of bortezomib would be made for patients with adequate response as per Blade criteria and continue until disease progression or 18 months

Genentech, Inc.

Hackensack Meridian Health

Overall Survival (OS) - Overall Survival is Calculated at the Time of the Screening Evaluation to Death From Any Cause.

Drug Combination

Age, Categorical

Sex: Female, Male

7 subjects were consented 6 proceeded with treatment, 4 completed study: one failed screening and one was dropped due to non-compliance with protocol, one withdrew consent

The study was terminated prior to enrollment completion and formal analysis of the primary objectives was never conducted.

Dr. David Siegel

Bortezomib and Bevacizumab

Median Number of Cycles to Tumor Progression (TTP)

Bortezomilb will be administered at 1.3 mglm2 IVP on Days 1. 4, 8, and 11. Response will be assessed subsequent to each cycle. A total of 8 cycles would beplanned. Patients would be removed subsequent to Cycle 2. if progression of disease is documented.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Study of hLL1-DOX (Milatuzumab-Doxorubicin Antibody-Drug Conjugate) in Patients With Multiple Myeloma	NCT01101594	Multiple Myelom...	hLL1-DOX (the d...	18 Years -	Gilead Sciences
A Study of hLL1-DOX (Milatuzumab-Doxorubicin Antibody-Drug Conjugate) in Patients With Multiple Myeloma	NCT01101594	Multiple Myelom...	hLL1-DOX (the d...	18 Years -	Gilead Sciences
A Phase II Study of Bevacizumab and Bortezomib in Patients With Relapsed/Refractory Multiple Myeloma	NCT00464178	Multiple Myelom...	Bortezomib	18 Years -	Hackensack Meridian Health

Spots Global Cancer Trial Database for relapsed, refractory multiple myeloma