Mezigdomide Plus Ixazomib and Dexamethasone for Relapsed and Refractory Multiple Myeloma

Sponsor
Kathleen Dorritie
Study ID
NCT06050512
Phase
PHASE1/PHASE2
Status
Withdrawn

Conditions

  • Relapsed and Refractory Multiple Myeloma

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Mezigdomide — DRUG
    Mezigdomide (MEZI), a novel oral CELMoD® agent with enhanced tumoricidal and immune-stimulatory effects compared to immunomodulatory drugs (IMiDs®), induces maximal degradation of Ikaros and Aiolos, leading to increased apoptosis in myeloma cells.
  • Ixazomib — DRUG
    Ixazomib, a second-generation proteasome inhibitor, is used primarily in the treatment of multiple myeloma. This activity outlines the mechanism of action, indications, and contraindications for ixazomib as a valuable agent for treating multiple myeloma.
  • Dexamethasone — DRUG
    Corticosteroids, such as dexamethasone and prednisone, are an important part of the treatment of multiple myeloma. They can be used alone or combined with other drugs as a part of treatment. Corticosteroids are also used to help decrease the nausea and vomiting that chemo might cause.

Study Details

Multiple myeloma (MM) is the second most common hematologic malignancy with an estimated annual incidence of nearly 35,000 cases. While still considered an incurable disease, new treatments have improved outcomes dramatically over the last two decades. Around the turn of the millennium, classical cytotoxic chemotherapy and radiation were the only available treatment modalities and median OS was estimated at 2-3 years. Currently, there are now 17 FDA-approved anti-myeloma agents and median OS is approaching 10 years. More recently, next generation cellular and immune therapies are demonstrating unprecedented efficacy in highly refractory patients with otherwise a very short life expectancy. In this study, the starting dose of ixazomib will be reduced to 3mg, as this is the first FDA-recommended dose recommendation (from 4mg). The starting dose of mezigdomide will be 0.6mg. Frequent toxicity and AE monitoring as outlined in this trial (weekly in C1, every 2 weeks in C2-C4) asserts maximization of patient safety. Dexamethasone (DEX) will be dosed at 40mg weekly in patients \< 75 years old and 20mg for patients \> 76 years old. Additionally, the staring dose of DEX may be reduced to 20mg in any patient, per study provider discretion, based on several factors such frailty, prior adverse side effects or existing comorbidities.

Key Dates

Start date
Oct 2, 2023
Status verified
Nov 2024
Primary completion
Oct 31, 2026
Completion
Oct 31, 2026

Study Design

Enrollment
0 participants (actual)
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT

Arms

  • Experimental: Phase l: Mezigdomide + Ixazomib + Dexamethasone
    Dose level -2: Mezigdomide: 0.3 mg daily on days 1-21 of a 28-day schedule; Ixazomib: 2.3 mg PO weekly on days 1, 8 and 15 of a 28-day schedule; Dexamethasone: 40 or 20 mg on days 1, 8, 15 and 22 Dose level -1: Mezigdomide: 0.6 mg daily on days 1-21 of a 28-day schedule; Ixazomib: 2.3 mg PO weekly on days 1, 8 and 15 of a 28-day schedule; Dexamethasone: 40 or 20 mg on days 1, 8, 15 and 22 Dose level 0 (Starting dose): Mezigdomide: 0.6 mg daily on days 1-21 of a 28-day schedule; Ixazomib: 3.0 mg PO weekly on days 1, 8 and 15 of a 28-day schedule; Dexamethasone: 40 or 20 mg on days 1, 8, 15 and 22 Dose level +1: Mezigdomide: 1.0 mg daily on days 1-21 of a 28-day schedule; Ixazomib: 3.0 mg PO weekly on days 1, 8 and 15 of a 28-day schedule; Dexamethasone: 40 or 20 mg on days 1, 8, 15 and 22 Dose level +2: Mezigdomide: 1.0 mg daily on days 1-21 of a 28-day schedule; Ixazomib: 4.0 mg PO weekly on days 1, 8 and 15 of a 28-day schedule; Dexamethasone: 40 or 20 mg on days 1, 8, 15 and 22
  • Experimental: Phase ll (RP2D): Mezigdomide + Ixazomib + Dexamethasone
    Mezigdomide: RP2D daily on days 1-21 of a 28-day schedule Ixazomib: RP2D PO weekly on days 1, 8 and 15 of a 28-day schedule Dexamethasone: RP2D on days 1, 8, 15 and 22

Primary Outcome Measure

Phase l: Recommended Phase II Dose (RP2D) [ Time Frame: Up to 17 months ]

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