Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Neoplasms by Histologic Type

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Anti-Inflammatory Agents

Antineoplastic Agents

Antiemetics

Gastrointestinal Agents

All Drugs and Chemicals

Antipyretics

Analgesics

Anti-Allergic Agents

Central Nervous System Depressants

Dermatologic Agents

Respiratory System Agents

Dexamethasone

Acetaminophen

Daratumumab

Dexamethasone acetate

Diphenhydramine

Promethazine

Montelukast

Glucocorticoids

Hormones

Hormone Antagonists

Antineoplastic Agents, Hormonal

Analgesics, Non-Narcotic

Anti-Asthmatic Agents

Leukotriene Antagonists

Hypnotics and Sedatives

Anesthetics

Anesthetics, Local

Histamine H1 Antagonists

Histamine

Histamine phosphate

Histamine Antagonists

Neurotransmitter Agents

Prior to Iber-KDd combination therapy, participants will receive Acetaminophen, Diphenhydramine and Montelukast therapy per protocol. Participants will receive up to eight (8) 28-day cycles of combination Iberdomide (I), Carfilzomib (K), Daratumumab (D), and Dexamethasone (d) (Iber-KDd) therapy. Participants will receive Iber-KDd combination therapy for approximately 8 months. In the absence of disease progression, participants will continue on to Iber monotherapy. Participants with disease progression will discontinue study therapy but will continue to be followed for up to three (3) years after conclusion of Iber-KDd combination therapy.

After completion of Iber-KDd combination therapy, and In the absence of disease progression, participants will then receive up to twelve (12) 28-day cycles of Iberdomide (Iber) monotherapy. Participants will receive Iber monotherapy for up to 12 months or until disease progression. Participants will be followed for up to three (3) years after conclusion of Iber monotherapy. Total study participation is up to five (5) years.

Participants will receive Iberdomide (Iber) therapy orally (PO) in capsules as follows:

* Combination therapy: Cycles 1 to 8: 1 mg per day\*, Days 1 to 21 every 28 days.
* Monotherapy: Cycles 9 to 20: 1 mg per day\*, Days 1 to 21 every 28 days.

(\*) The first 6 patients will begin at 1 mg/day as lead-in with option to increase to 1.3 mg with dose-escalation cohort after two (2) cycles tolerated therapy

Iberdomide

Participants will receive Carfilzomib (K) therapy intravenously (IV) as follows:

* Cycle 1: 20 mg/m2 per dose on Day 1; 56 mg/m2 per dose on Days 8 and 15
* Cycles 2 to 8: 56 mg/m2 per dose on Days 1, 8, and 15.

Carfilzomib

Participants will receive Daratumumab (D) therapy subcutaneously (SC) or intravenously (IV) as follows:

* Cycles 1 and 2: 1800 mg SC or 16 mg/kg IV on Days 1, 8, 15, and 22
* Cycles 3 through 6: 1800 mg SC or 16 mg/kg IV on Days 1 and 15
* Cycles 7 and 8: 1800 mg SC or 16 mg/kg IV on Day 1.

Participants will receive Dexamethasone (d) therapy either orally (PO) or intravenously (IV) as follows:

* Cycles 1 and 2: 40 mg/dose on Days 1, 8, and 15; 20 mg/dose on Day 22
* Cycles 3 and 4: 40 mg/dose on Days 1, 8, and 15
* Cycles 5 through 8: 20 mg/dose on Days 1, 8, and 15.

Participants will receive Acetaminophen orally (PO) prior to Iber-KDd therapy as follows:

* Cycles 1 and 2: 650 mg/dose on Days 1, 8, 15, and 22
* Cycles 3 through 6: 650 mg/dose on Days 1 and 15
* Cycles 7 and 8: 650 mg/dose on Day 1.

Participants will receive Diphenhydramine either orally (PO) or intravenously (IV) prior to Iber-KDd therapy as follows:

* Cycles 1 and 2: 25 mg/dose on Days 1, 8, 15, and 22
* Cycles 3 through 6: 25 mg/dose on Days 1 and 15
* Cycles 7 and 8: 25 mg/dose on Day 1.

Participants will receive Montelukast orally (PO) prior to Iber-KDd as follows:

* Cycle 1 only: 10 mg/dose, Days 1, 8, 15, and 22, to be administered prior to the first 4 doses of Daratumumab (D).

Michelle D Armogan

Carl O Landgren, MD, PhD

Benjamin Diamond, MD

The investigators want to find out whether or not giving patients who have relapsed or refractory multiple myeloma (MM) the experimental medication combination iberdomide, carfilzomib, daratumumab, and dexamethasone (Iber-KDd) may produce better results than the current (standard of care) treatments. This study will examine the tolerability and efficacy of this combination therapy for all participants and the ability of this combination therapy to shrink or prevent MM from returning.

Iberdomide, Daratumumab, Carfilzomib, and Dexamethasone (Iber-KDd) in Patients With Relapsed/Refractory Multiple Myeloma

Phase 2, Single-Arm Study of Iberdomide, Daratumumab, Carfilzomib, and Dexamethasone (Iber-KDd) in Patients With Relapsed/Refractory Multiple Myeloma

The rate of minimal residual disease negativity (MRD-negativity) will be reported as the number of participants achieving MRD-negativity after eight cycles of Iber-KDd combination therapy. MRD-negativity is defined as less than one (\<1) residual cancer cell detected in 100,000 cells assessed.

The safety and tolerability of Iber-KDd combination therapy will be assessed and reported as the number of participants experiencing treatment-related toxicity after start of combination therapy, including treatment-related adverse events (AEs) and serious adverse events (SAEs). AEs and SAEs will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5, per physician discretion.

Best response will be reported as the proportion of participants achieving their greatest response to Iber-KDd combination therapy as follows: Partial response (PR) or better, very good partial response (VGPR) or better, complete response (CR), and stringent complete response (sCR). Response will be assessed using the International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma.

Overall response rate (ORR) is defined as the number of participants achieving partial response (PR), very good partial response (VGFR)m complete response (CR) or stringent complete response (sCR) to Iber-KDd combination therapy. Response will be assessed using the International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma.

Best response will be reported as the proportion of participants achieving their greatest response to Iberdomide monotherapy as follows: Partial response (PR) or better, very good partial response (VGPR) or better, complete response (CR), and stringent complete response (sCR). Response will be assessed using the International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma.

Overall response rate (ORR) is defined as the number of participants achieving partial response (PR), very good partial response (VGFR)m complete response (CR) or stringent complete response (sCR) to Iberdomide monotherapy. Response will be assessed using the International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma.

Duration of Response (DOR) to Iber-KDd combination therapy will be assessed. Duration of response (DOR) is defined as time from response to progression of disease or death, whichever occurs first.

Overall survival (OS) is defined as the time from date of first dose of study treatment to death from any cause.

Progression-free survival (PFS) is defined as time from date of first dose of study treatment to time of progression or death, whichever occurs first.

Event-free survival (EFS) is defined as time from date of first dose of study treatment until 1) toxicity requiring removal from study, 2) progression, or 3) death, whichever occurs first.

The rate of sustained minimal residual disease negativity (MRD-negativity) at the completion combination Iber-KDd therapy and 12 cycles of iberdomide monotherapy will be assessed. MRD-negativity is defined as less than one (\<1) residual cancer cell detected in 100,000 cells assessed. The number of participants will sustained Response will be assessed using the International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma.

The rate of MRD-negativity as best response will be assessed among participants completing Iberdomide monotherapy. The number of participants with MRD-negativity at the 10\^-5 sensitivity will be reported. MRD-negativity is defined as less than one (\<1) residual cancer cell detected in 100,000 cells assessed. Response will be assessed using the International Myeloma Working Group (IMWG) Response Criteria for Multiple Myeloma.

The safety and tolerability of Iber monotherapy will be assessed and reported as the number of participants experiencing treatment-related toxicity after start of monotherapy, including treatment-related adverse events (AEs) and serious adverse events (SAEs). AEs and SAEs will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5, per physician discretion.

Spots Global Cancer Trial Database for Iberdomide, Daratumumab, Carfilzomib, and Dexamethasone (Iber-KDd) in Patients With Relapsed/Refractory Multiple Myeloma

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