This phase I/II trial studies the safety, side effects, best dose, and effectiveness of iberdomide in combination with daratumumab and hyaluronidase-fihj, dexamethasone, and carfilzomib after autologous hematopoietic cell transplantation (AHCT) to eliminate minimal residual disease (MRD) in patients with multiple myeloma (MM). MRD is MM cells at very low level only detectable using a specially developed test utilizing a bone marrow sample. The presence of MRD after AHCT indicates higher risk of the myeloma returning or worsening. It has not yet been determined if more anti-myeloma treatment that makes the MRD non-detectable improves the patient’s survival or duration of myeloma control. Immunotherapy with iberdomide, may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Daratumumab is in a class of medications called monoclonal antibodies. It works by helping the body to slow or stop the growth of cancer cells. Hyaluronidase-fihj is an endoglycosidase. It helps to keep daratumumab in the body longer so that the medication will have a greater effect. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Carfilzomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving iberdomide in combination with daratumumab and hyaluronidase-fihj, dexamethasone, and carfilzomib after AHCT may reduce the number of circulating cancer cells detected in the blood in patients with MM.
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT05434689.
PRIMARY OBJECTIVES:
I. 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 (>= 10^-5) (Part I):
Ia. Regimen A: Iberdomide, daratumumab and dexamethasone (Part I);
Ib. Regimen B: Iberdomide, daratumumab, carfilzomib and dexamethasone (if regimen A is considered safe) (Part I).
II. To determine the efficacy of regimens A and B in post AHCT consolidation as assessed by conversion of MRD (to < 10^-5) (Part II).
SECONDARY OBJECTIVES:
I. To determine the sustainability of MRD (-) status achieved with regimen A or B.
II. To estimate the achievement of MRD <10^-6 with regimens A and B.
III. To determine the safety and tolerability of regimens A and B when utilized as post-AHCT consolidation.
IV. To estimate the risk of death or disease progression of patients treated with regimen A or B as post-AHCT consolidation.
OUTLINE: This is phase I, dose-escalation study of iberdominde followed by a phase II study.
PART 1 CONSOLIDATION THERAPY: Patients are assigned to 1 of 2 arms.
ARM I: Patients receive iberdomide orally (PO) on days 1-21 and dexamethasone PO or intravenously (IV) on days 1,8,15 and 22 of each cycle. Patients also receive daratumumab and hyaluronidase-fihj subcutaneously (SC) on days 1, 8, 15, 22 of cycles 1 and 2 or on days 1 and 15 of cycles 3-6. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo echocardiography (ECHO) during screening and bone marrow aspiration during Part 1 of the study. Patients also undergo blood and urine sample collection throughout Part 1 of the study. Patients completing 6 cycles without disease progression and unacceptable toxicity and receiving clinical benefit have the option to proceed to Part 2 Continuation Therapy.
ARM II: Patients receive iberdomide PO on days 1-21, dexamethasone PO or IV on days 1,8,15 and 22, and carfilzomib IV over 30 minutes on days 1, 8, and 15 of each cycle. Patients also receive daratumumab and hyaluronidase-fihj SC on days 1, 8, 15, 22 of cycles 1 and 2 or on days 1 and 15 of cycles 3-6. Treatment repeats every 28 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO during screening and bone marrow aspiration Part 1 of the study. Patients also undergo blood and urine sample collection throughout Part 1 of the study. Patients completing 6 cycles without disease progression and unacceptable toxicity and receiving clinical benefit have the option to proceed to Part 2 Continuation Therapy.
PART 2 CONTINUATION THERAPY: Patients receive iberdomide PO on days 1-21 of each cycle. Treatment repeats every 28 days for up to 26 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo bone marrow aspiration and undergo blood and urine sample collection throughout Part 2 of the study.
Patients are followed for up to 2 years from completion of Consolidation Therapy.
Lead OrganizationUniversity of Alabama at Birmingham Cancer Center
Principal InvestigatorLuciano Jose Megale Costa
