Neoplasms

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Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

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Hematologic Diseases

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Anti-Inflammatory Agents

Antineoplastic Agents

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Gastrointestinal Agents

All Drugs and Chemicals

Dexamethasone

Pomalidomide

Dexamethasone acetate

Elotuzumab

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Immunologic Factors

Angiogenesis Inhibitors

Growth Inhibitors

Drug dosing and administration:

All drugs are administered on a 28-day cycle.

Elotuzumab: 10 mg/kg IV on Days 1,8,15 and 22 Cycles 1 and 2. 20 mg/kg on Day 1 of Cycles 3 and beyond.

Pomalidomide: 3 mg PO on days 1-21

Carfilzomib: 20 mg/m2 IV on days 1 of cycle 1. 56 mg/m2 IV on days 8 and 15 of cycle 1 and Days 1, 8 and 15 of the remaining seven cycles.

Dexamethasone: On days 1,8,15,22 of Cycle 1-2 and day 1 of Cycle 3 and every day 1 thereafter, pre-treatment with 28 mg PO 3-24 hours prior to the start of ELO. On days 8,15,22 of Cycle 3 and beyond, 40mg of DEX PO or IV. On Day 8 and 15 of Cycle 3 and beyond, pre-treatment with DEX 40mg PO or IV at least 30 min and no more than 4 hours prior to the start of CFZ.

Elotuzumab IV at 10mg/kg Elotuzumab IV at 20mg/kg

Carfilzomib 20mg/m2 IV Carfilzomib 56mg/m2 IV

Carfilzomib

Dexamethasone 28mg PO Dexamethasone 40mg PO or IV Dexamethasone 8mg IV

James R Berenson, MD

Despite the recent introduction of novel anti-multiple myeloma (MM) agents, high risk MM remains with poor prognosis and a therapeutic challenge. Elotuzumab (ELO) is a humanized monoclonal antibody that recognizes CS1/CD139, a molecule highly expressed in MM cells. The ELO (10 mg/kg), lenalidomide (LEN) and dexamethasone (DEX) combination achieves high overall response rates (ORR) and long progression-free survival (PFS) for patients with relapsed/refractory disease (RR) MM and those with impaired renal function. However, its efficacy for MM patients with high risk characteristics is still unknown. Pomalidomide (POM) is a recently approved immunomodulatory agent (IMiD) that produces response rates for high-risk RRMM patients when used in combination with DEX and other agents, including the proteasome inhibitor (PI) bortezomib (BTZ). POM has also demonstrated activity for LEN refractory patients. Carfilzomib (CFZ) is a potent second generation PI that has shown to be efficacious for IMiD and BTZ refractory patients as well as high risk patients carrying cytogenetic abnormalities. In this study, we propose to evaluate efficacy and safety of ELO in combination with POM, DEX and CFZ for high-risk RRMM patients.

This is a Phase 2, multicenter, open label, nonrandomized study with six patients safety lead-in cohort to evaluate efficacy and safety of elotuzumab in combination with pomalidomide, carfilzomib and dexamethasone among high risk relapsed and refractory multiple myeloma patients.

This study will enroll previously treated patients that currently show evidence of progressive disease and have been diagnosed with high risk multiple myeloma. Thirty-nine patients will be enrolled in the study.

First, six patients will be enrolled and used as a lead-in cohort for the safety evaluation and MTD re-determination (if necessary). The results of the safety lead-in cohort will be evaluated after the 6th patient has completed one full cycle of treatment. Recruitment of patients will be withheld during safety data analysis. Enrollment of the remaining 33 patients will be contingent upon safety committee's decision.

The study consists of: 1) a screening period; 2) up to eight 28-day treatment cycles; 3) a final assessment to occur 28 days after the end of the last treatment cycle; and 4) a follow-up period.

All drugs will be administered on a 28-day cycle schedule throughout the study. Subjects eligible for this study will receive treatment with study drug for a maximum of eight 28-day treatment cycles. Subjects are to be treated for 8 cycles of therapy without demonstrating PD.

Combination Study for High Risk Multiple Myeloma Patients

A Phase 2 Trial of the Efficacy and Safety of Elotuzumab in Combination With Pomalidomide, Carfilzomib and Dexamethasone Among High Risk Relapsed/ Refractory Multiple Myeloma Patients

Occurrence of adverse events throughout the study, graded via Common Terminology Criteria for Adverse Events (CTCAE) v 4.03 criteria (If necessary re-define MTD via the number of dose-limiting toxicities (DLTs) per dose level, of elotuzumab in combination with pomalidomide, carfilzomib and dexamethasone for high risk RRMM patients (based on six patients lead-in cohort if necessary).

Efficacy of treatment will be assessed by the Overall response rate (ORR) \[ORR=complete response (CR†) + very good partial response (VGPR) + partial response (PR)\] Clinical benefit rate (CBR) \[CBR=CR† + VGPR + PR + minor response (MR)\].

Progression-free survival (PFS): time from initiation of therapy to progressive disease or death from any cause, whichever comes first

Duration of response (DOR): time from the first response (\> PR) to progressive disease

Overall survival (OS): time from initiation of therapy to death from any cause or last follow-up visit.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combination Study for High Risk Multiple Myeloma Patients	NCT03104270	Multiple Myelom...	Elotuzumab Pomalidomide Carfilzomib Dexamethasone	18 Years -	Oncotherapeutics
Combination Study for High Risk Multiple Myeloma Patients	NCT03104270	Multiple Myelom...	Elotuzumab Pomalidomide Carfilzomib Dexamethasone	18 Years -	Oncotherapeutics
Combination Study for High Risk Multiple Myeloma Patients	NCT03104270	Multiple Myelom...	Elotuzumab Pomalidomide Carfilzomib Dexamethasone	18 Years -	Oncotherapeutics

Spots Global Cancer Trial Database for elotuzumab, multiple myeloma, phase 2