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Clinical Trial Summary

This phase I/II trial studies the best dose and side effects of venetoclax and how well it works in combination with ixazomib and dexamethasone in treating patients with t(11;14) negative multiple myeloma that has come back or does not respond to treatment. Ixazomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as venetoclax and dexamethasone work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known how well venetoclax works with ixazomib and dexamethasone in treating patients with multiple myeloma.


Clinical Trial Description

PRIMARY OBJECTIVES:

I. To evaluate the safety profile and tolerability of oral combination therapy with ixazomib citrate (ixazomib) (I), venetoclax (V), dexamethasone (D) in non-t(11;14) relapsed/refractory multiple myeloma (RRMM) with dose-escalating design to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D). (Phase I) II. To compare overall response rate (ORR; measured as best response) of IVD and ID in a proteasome inhibitor (PI)-non-refractory cohort. (Phase II, Cohort 1) III. To evaluate ORR of IVD in PI-refractory cohort. (Phase II, Cohort 2)

SECONDARY OBJECTIVES:

I. To observe and record anti-tumor activity. II. To determine the rate of very good partial response (VGPR) or better. III. To determine time to progression (TTP). IV. To determine duration of response (DOR). V. To determine progression-free survival (PFS). VI. To determine overall survival (OS).

EXPLORATORY OBJECTIVES:

I. To correlate and predict responses with the following tests, using bone marrow aspirate samples at (a) baseline and (b) during treatment on day 8 (or day 9 to allow for scheduling flexibility): BCL2, NOXA, and MCL1 by flow cytometry; polymerase chain reaction (PCR) for BCL2, BCL2L1 (=BCL-XL), and MCL-1 messenger ribonucleic acid (mRNA) expression, and BCL2:BCL2L1 and BCL2:MCL1 ratios; and Ex vivo Mathematical Myeloma Advisor (EMMA).

II. To evaluate the drug exposure and to correlate with toxicities using venetoclax peripheral blood pharmacokinetic (PK) analysis.

OUTLINE: This is a phase I, dose-escalation study of venetoclax followed by a phase II study. PI non-refractory patients are randomized to 1 of 2 arms.

ARM I: Patients receive ixazomib citrate orally (PO) on days 1, 8, and 15, venetoclax PO once daily (QD) on days 1-28 and dexamethasone PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive ixazomib citrate PO on days 1, 8, and 15, and dexamethasone PO on days 1, 8, 15, and 22. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM III: PI-refractory patients receive ixazomib citrate, venetoclax and dexamethasone as Arm I.

After completion of study treatment, patients are followed for 30 days. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03856112
Study type Interventional
Source National Cancer Institute (NCI)
Contact
Status Withdrawn
Phase Phase 1/Phase 2
Start date June 21, 2019
Completion date December 31, 2021

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