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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT03770260
Other study ID # NCI-2018-03121
Secondary ID NCI-2018-0312110
Status Completed
Phase Phase 1
First received
Last updated
Start date February 10, 2020
Est. completion date July 6, 2023

Study information

Verified date August 2023
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This phase Ib trial studies side effects and best dose of pevonedistat when given together with ixazomib in treating patients with multiple myeloma that has come back or does not respond to treatment. Pevonedistat and ixazomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.


Description:

PRIMARY OBJECTIVES: I. Determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of MLN4924 (pevonedistat) in combination with MLN9708 (ixazomib citrate [ixazomib]) in relapsed and/or refractory multiple myeloma (RRMM) patients after more than one previous line of treatment. (Dose-escalation phase) II. Describe the safety profile and tolerability of the combination of MLN9708 (ixazomib) and MLN4924 (pevonedistat) in the proteasome inhibitor (PI)-sensitive and PI-refractory populations. (Dose-expansion phase) III. Determine the anti-tumor activity and overall response rates (ORR) in patients with RRMM with the use of MLN9708 (ixazomib) and MLN4924 (pevonedistat) in combination. (Dose-expansion phase) SECONDARY OBJECTIVE: I. Attain pharmacokinetic (PK) characterization of MLN4924 (pevonedistat) in combination with MLN9708 (ixazomib) for the purpose of understanding concentration-effect relationships of both agents. (Dose-escalation phase) EXPLORATORY OBJECTIVE: I. To correlate and predict disease response using the following tests: NAD(P)H dehydrogenase (quinone) 1 (NQO1) and cystine/glutamate transporter (SLC7A11) (nuclear factor [erythroid-derived 2]-like 2 [NRF2] target genes): evaluated on whole blood as markers of MLN4924 (pevonedistat) activity. OUTLINE: This is a dose-escalation study of pevonedistat. Patients receive ixazomib citrate orally (PO) once daily (QD) on days 1, 8, and 15 of each cycle and pevonedistat intravenously (IV) over 60 minutes on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days, then every 2-3 months for up to 2 years.


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Study Design


Intervention

Drug:
Ixazomib Citrate
Given PO
Pevonedistat
Given IV

Locations

Country Name City State
United States Emory University Hospital/Winship Cancer Institute Atlanta Georgia
United States Ohio State University Comprehensive Cancer Center Columbus Ohio
United States Duke University Medical Center Durham North Carolina
United States University of Kentucky/Markey Cancer Center Lexington Kentucky
United States Smilow Cancer Center/Yale-New Haven Hospital New Haven Connecticut
United States Yale University New Haven Connecticut
United States Moffitt Cancer Center Tampa Florida
United States Moffitt Cancer Center - McKinley Campus Tampa Florida
United States Moffitt Cancer Center-International Plaza Tampa Florida

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Number of Participants Experiencing a Dose Limiting Toxicity (Dose Escalation) Number of participants experiencing a dose limiting toxicity to determine the maximum tolerated dose (MTD) At Day 28
Primary Number of Participants Experiencing a Grade 3-5 Adverse Event (Dose Expansion) Number of participants who experienced a grade 3-5 adverse event in the dose expansion group Up to 2 years after Treatment
Primary Overall Response Rate (Dose Expansion) To determine the overall responses in patients receiving pevonedistat and ixazomib Up to 2 Years after Treatment
Secondary Characterize the Pharmacokinetics (PK) of Pevonedistat and Ixazomib (Dose Escalation) To understand the concentration-effect relationship of both agents when taken together Up to 3 months
See also
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