Venetoclax and Tocilizumab for t(11;14)

PRIMARY OBJECTIVE:

I. To determine the dose limiting toxicity (DLT), safety profile, and the recommended phase 2 dose (RPTD) of venetoclax and tocilizumab when administered in subjects with relapsed and recurrent (RR) multiple myeloma t(11;14) (MM).

SECONDARY OBJECTIVES:

I. To evaluate the preliminary efficacy data regarding the effect of venetoclax and tocilizumab by objective response rate per IMWG criteria.

II. To evaluate the effect of chronic tocilizumab administration on venetoclax exposure.

TERTIARY/EXPLORATORY OBJECTIVES:

I. To evaluate the preliminary efficacy data regarding the effect of venetoclax and tocilizumab by time to response (TTR), time to disease progression (TTP), duration of response (DOR), progression free survival (PFS) and overall survival (OS).

II. To measure the effect of IL6 receptor blockade on ex vivo venetoclax sensitivity.

III. To evaluate the cell populations in the bone marrow of responders versus non-responders as well as the effect of IL6 receptor blockade on those populations.

IV. To evaluate the expression of B cell markers on venetoclax sensitive myeloma.

V. To determine the expression of key BCL2 family members with and without IL6 receptor blockade.

VI. To correlate differences in somatic mutations, structural alterations, gene expression and chromatin accessibility with venetoclax response.

OUTLINE: This is a dose-escalation study of venetoclax and tocilizumab.

Patients receive tocilizumab intravenously (IV) on day -7 of cycle 1, and on day 1 of subsequent cycles. Patients also receive venetoclax orally (PO) on days 1-21. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks, then every 6 months thereafter.