Title
Phase Ib/II Trial of Iberdomide-Combinations in Patients With Positive Minimal Residual Disease (>10-5) After Autologous Hematopoietic Cell Transplantation in the Upfront Management of Patients With Multiple Myeloma

Description
Similar to the paradigm established in other hematologic malignancies that are considered curable, the achievement of MRD(-) status is necessary for long term disease control in MM. The fact that the majority of patients remain MRD (+) after induction therapy and AHCT points to the opportunity to deploy novel agents with complementary mechanism of action and favorable toxicity profile to reach and maintain MRD (-) status.

Given its favorable toxicity profile, the convenience of oral administration, and compelling single agent activity even in heavily pretreated MM, iberdomide is likely amenable to long term therapy in patients with high-risk of relapse/progression identified by the persistence of MRD(+). The investigators intend to develop combination(s) of iberdomide with other agents with complementary mechanism of action in the consolidation setting post AHCT in order to achieve and sustain MRD (-).

Objective
Primary Objectives:
-Part 1: To determine the safety and recommended phase 2 dose (RP2D) of the following iberdominde combinations when employed as consolidation therapy post autologous hematopoietic cell transplantation (AHCT) in MRD(+) patients [greater than or equal to (0.00001)/(10 clonogenic sequences/1,000,000 cells)]:
--Regimen A: Iberdomide, daratumumab and dexamethasone
--Regimen B: Iberdomide, daratumumab, carfilzomib and dexamethasone (if regimen A is considered safe).

-Part 2: To determine the efficacy of regimens A and B in post AHCT consolidation as assessed by conversion of MRD (to < 0.00001).

Secondary Objectives:
-To Determine the sustainability of MRD (-) status achieved with regimen A or B
-To estimate the achievement of MRD < 0.000001 with regimens A and B
-To determine the safety and tolerability of regimens A and B when utilized as post-AHCT consolidation.
-To estimate the risk of death or disease progression of patients treated with regimen A or B as post-AHCT consolidation.

Treatment Experimental: Iberdomide, Daratumumab and Dexamethasone (Regimen A)
Iberdomide dosed according to cohort assignment days 1-21. Dexamethasone 40 mg oral or intravenously (20 mg for participants 70 or older) on days 1,8,15 and 22 Darartumumab and hyalurnonidase-fihj 1,800mg/30,000 units subcutaneously on days 1,8,15,22 (cycles 1,2) or on days 1,15 (cycles 3-6)

Experimental: Iberdomide, Carfilzomib, Daratumumab and Dexamethasone (Regimen B)
Iberdomide dosed according to cohort assignment days 1-21. Dexamethasone 40 mg oral or intravenously (20 mg for participants 70 or older) on days 1,8,15 and 22 Darartumumab and hyalurnonidase-fihj 1,800mg/30,000 units subcutaneously on days 1,8,15,22 (cycles 1,2) or on days 1,15 (cycles 3-6) Carfilzomib dosed intravenously dosed according to cohort assignment on days 1, 8, 15.

Key Eligibility For full study eligibility, see this study's ClinicalTrials.gov record.

Applicable Disease Sites
Multiple Myeloma

Participating Institutions
UW Health 1 S. Park Medical Center; UW Health Eastpark Medical Center; UW Health University Hospital