Carfilzomib, Iberdomide (CC-220) and Dexamethasone (KID) in Transplant Eligible Multiple Myeloma

NCT05199311 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: Pro2021-0842
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 2

Brief Summary

This is a multi-institution, open label, phase I/II study of Iberdomide, Carfilzomib, and dexamethasone (KID) in patients with newly diagnosed transplant eligible MM.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (2)

• Rate of treatment emergent adverse events (TEAEs)

  Rate of patients with treatment emergent adverse events (TEAEs) overall and per dose level

  Measured after cycle 4 of induction KID (each cycle is 28 days)

• CR and sCR

  Evaluation of the rate of complete remission (CR) + stringent complete (sCR) remission for patients receiving 2-4 cycles of the combination of KID followed by ASCT in patients with newly diagnosed MM.

  Measured after cycle 4 of induction KID (each cycle is 28 days)

Secondary Outcomes (3)

• Overall Response Rate (ORR)

  Participants will be followed for response assessment every 28 days until progression of disease or a subsequent myeloma regimen has been started. On treatment study duration will last up to 12 months; Post treatment follow up will last up to two years.

• Progression Free Survival (PFS)

  Participants will be followed for response assessment every 28 days until progression of disease or a subsequent myeloma regimen has been started. On treatment study duration will last up to 12 months; Post treatment follow up will last up to two years.

• Overall Survival (OS)

  Participants will be followed for response assessment every 28 days until progression of disease or a subsequent myeloma regimen has been started. On treatment study duration will last up to 12 months; Post treatment follow up will last up to two years.

Study Arms (4)

Starting Dose -1

EXPERIMENTAL

CC-220/Iberdomide: 1.1 mg \[CC-220 dosing schedule: daily for 21 days of each 28-day cycle\] Carfilzomib: 20 mg/m2 C1D1 56 mg/m2 thereafter \[Days 1, 8, 15 per 28-day cycle\] Dexamethasone: 40 mg (≤ 75 years) 20 mg (\> 75 years) \[Days 1, 8, 15, 22 per 28-day cycle\] Treatment will continue with carfilzomib, iberdomide, and dexamethasone for up to 4 cycles (28 days) at the physician's discretion followed by the Autologous Stem Cell Transplant. Patients will be followed every 3 months for up to 2 years, or until PD or the start of a new line of therapy.

Drug: Carfilzomib; Drug: Iberdomide; Drug: Oral Dexamethasone

Dose Level 1

EXPERIMENTAL

CC-220/Iberdomide: 1.3 mg \[CC-220 dosing schedule: daily for 21 days of each 28-day cycle\] Carfilzomib: 20 mg/m2 C1D1 56 mg/m2 thereafter \[Days 1, 8, 15 per 28-day cycle\] CC-220 dose level 1 enrollment will occur following an independent safety review two months after the first 10 patients have completed at least 2 cycles of therapy at dose level -1. Dexamethasone: 40 mg (≤ 75 years) 20 mg (\> 75 years) \[Days 1, 8, 15, 22 per 28-day cycle\] Treatment will continue with carfilzomib, iberdomide, and dexamethasone for up to 4 cycles (28 days) at the physician's discretion followed by the Autologous Stem Cell Transplant. Patients will be followed every 3 months for up to 2 years, or until PD or the start of a new line of therapy.

Drug: Carfilzomib; Drug: Iberdomide; Drug: Oral Dexamethasone

Dose Level 2

EXPERIMENTAL

CC-220/Iberdomide: 1.6 mg \[CC-220 dosing schedule: daily for 21 days of each 28-day cycle\] Carfilzomib: 20 mg/m2 C1D1 56 mg/m2 thereafter \[Days 1, 8, 15 per 28-day cycle\] CC-220 dose level 2 enrollment will occur following an independent safety review two months after the first 10 patients have completed at least 2 cycles of therapy at dose level 1. Dexamethasone: 40 mg (≤ 75 years) 20 mg (\> 75 years) \[Days 1, 8, 15, 22 per 28-day cycle\] Treatment will continue with carfilzomib, iberdomide, and dexamethasone for up to 4 cycles (28 days) at the physician's discretion followed by the Autologous Stem Cell Transplant. Patients will be followed every 3 months for up to 2 years, or until PD or the start of a new line of therapy.

Drug: Carfilzomib; Drug: Iberdomide; Drug: Oral Dexamethasone

Dose Level -2

EXPERIMENTAL

CC-220/Iberdomide: 0.75 mg \[CC-220 dosing schedule: daily for 21 days of each 28-day cycle\] Carfilzomib: 20 mg/m2 C1D1 56 mg/m2 thereafter \[Days 1, 8, 15 per 28-day cycle\] Dexamethasone: 40 mg (≤ 75 years) 20 mg (\> 75 years) \[Days 1, 8, 15, 22 per 28-day cycle\] Treatment will continue with carfilzomib, iberdomide, and dexamethasone for up to 4 cycles (28 days) at the physician's discretion followed by the Autologous Stem Cell Transplant. Patients will be followed every 3 months for up to 2 years, or until PD or the start of a new line of therapy.

Drug: Carfilzomib; Drug: Iberdomide; Drug: Oral Dexamethasone

Interventions

Carfilzomib DRUG

20 mg/m2 C1D1; 56 mg/m2 thereafter

Dose Level -2; Dose Level 1; Dose Level 2; Starting Dose -1

Iberdomide DRUG

Oral CC-220 at dose specified by cohort dose level from Day 1-21 of each 28-day cycle

Dose Level -2; Dose Level 1; Dose Level 2; Starting Dose -1

Oral Dexamethasone DRUG

40 mg (\<=75 years old); 20 mg (\>75 years old)

Dose Level -2; Dose Level 1; Dose Level 2; Starting Dose -1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Documented newly diagnosed multiple myeloma
• a. At least 25% of patients accrued should be high risk as defined by IMWG or mSMART criteria.
• Patient should be deemed transplant eligible.
• Patients may not have had more than 1 cycle of prior induction therapy. If a patient has had 1 cycle of prior multiple myeloma therapy, the patient must have had documented measurable disease prior to initiation of cycle 1.
• Subjects must satisfy the following criteria to be enrolled in the study:
• Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF).
• Subject must understand and voluntarily sign an ICF prior to any study-related assessments/procedures being conducted.
• Subject is willing and able to adhere to the study visit schedule and other protocol requirements.
• Subjects must have a documented diagnosis of MM and have measurable disease defined as:
• M-protein (serum and/or urine protein electrophoresis (sPEP or uPEP)): sPEP≥0.5 g/dL or uPEP ≥ 200 mg/24 hours and/or
• Light chain MM without measurable disease in the serum or urine: serum immunoglobulin free light chain ≥ 10 mg/dL (100 mg/L) and abnormal serum immunoglobulin kappa lambda free light chain ratio
• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1 or 2.
• A female of childbearing potential (FCBP) is a female who: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral salpingectomy, or 3) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (ie, has had menses at any time in the preceding 24 consecutive months) and must:
• a. Have two negative pregnancy tests as verified by the Investigator prior to starting study treatment. She must agree to ongoing pregnancy testing during the course of the study, and after end of study treatment. This applies even if the subject practices true abstinence from heterosexual contact.
• Either commit to true abstinence from heterosexual contact (which must be reviewed on a monthly basis and source documented) or agree to use, and be able to comply with two forms of contraception: one highly effective, and one additional effective (barrier) measure of contraception without interruption 28 days prior to starting investigational product, during the study treatment (including dose interruptions), and for at least 28 days after the last dose of iberdomide.

You may not qualify if:

• Subject has any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from participating in the study
• Subject has any condition including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study
• Subject has any condition that confounds the ability to interpret data from the study
• Subject has nonsecretory multiple myeloma
• Subjects with Plasma Cell leukemia or amyloidosis (with the exception of isolated marrow involvement).
• Any of the following laboratory abnormalities:
• Absolute neutrophil count (ANC) \< 1,000/μL
• Platelet count \< 50,000/μL. It is not permissible to transfuse subjects to achieve minimum platelet counts.
• Corrected serum calcium \> 13.5 mg/dL (\> 3.4 mmol/L)
• Serum glutamic oxaloacetic transaminase (SGOT)/aspartate aminotransferase (AST) or serum glutamic pyruvic transaminase (SGPT)/alanine aminotransferase (ALT) ≥ 2.5 x upper limit of normal (ULN)
• Serum total bilirubin, direct bilirubin, or alkaline phosphatase ≥ 1.5 x ULN
• Subjects with serious renal impairment (\[CrCl\] \< 30 mL/min) or requiring dialysis would be excluded
• Subjects with peripheral neuropathy ≥ Grade 2
• Subjects with gastrointestinal disease that may significantly alter the absorption of iberdomide
• Subjects with a prior history of malignancies, other than MM, unless the subject has been free of the disease for ≥ 3 years with the exception of the following noninvasive malignancies:

Sponsors & Collaborators

• Hackensack Meridian Health: lead

Study Sites (2)

Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

RECRUITING

John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

RECRUITING

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• Ludwig H, Miguel JS, Dimopoulos MA, Palumbo A, Garcia Sanz R, Powles R, Lentzsch S, Ming Chen W, Hou J, Jurczyszyn A, Romeril K, Hajek R, Terpos E, Shimizu K, Joshua D, Hungria V, Rodriguez Morales A, Ben-Yehuda D, Sondergeld P, Zamagni E, Durie B. International Myeloma Working Group recommendations for global myeloma care. Leukemia. 2014 May;28(5):981-92. doi: 10.1038/leu.2013.293. Epub 2013 Oct 9.

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• Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, Sandhu I, Ganly P, Baker BW, Jackson SR, Stoppa AM, Simpson DR, Gimsing P, Palumbo A, Garderet L, Cavo M, Kumar S, Touzeau C, Buadi FK, Laubach JP, Berg DT, Lin J, Di Bacco A, Hui AM, van de Velde H, Richardson PG; TOURMALINE-MM1 Study Group. Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med. 2016 Apr 28;374(17):1621-34. doi: 10.1056/NEJMoa1516282.

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• Moreau P, San Miguel J, Sonneveld P, Mateos MV, Zamagni E, Avet-Loiseau H, Hajek R, Dimopoulos MA, Ludwig H, Einsele H, Zweegman S, Facon T, Cavo M, Terpos E, Goldschmidt H, Attal M, Buske C; ESMO Guidelines Committee. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2017 Jul 1;28(suppl_4):iv52-iv61. doi: 10.1093/annonc/mdx096. No abstract available.

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• Richardson PG, Siegel DS, Vij R, Hofmeister CC, Baz R, Jagannath S, Chen C, Lonial S, Jakubowiak A, Bahlis N, Song K, Belch A, Raje N, Shustik C, Lentzsch S, Lacy M, Mikhael J, Matous J, Vesole D, Chen M, Zaki MH, Jacques C, Yu Z, Anderson KC. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood. 2014 Mar 20;123(12):1826-32. doi: 10.1182/blood-2013-11-538835. Epub 2014 Jan 13.

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MeSH Terms

Conditions

Multiple Myeloma

Interventions

carfilzomib; iberdomide; Dexamethasone

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Study Officials

• Noa Biran, MD

  Hackensack Meridian Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Palka Anand

CONTACT

551-996-3040; Palka.Anand@hmhn.org

Kristin Ivanovski

CONTACT

551-996-5231; Kristin.Ivanovski@hmhn.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2021
• First Posted: January 20, 2022
• Study Start: May 13, 2022
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: February 18, 2026

Record last verified: 2026-02

Locations

US (2)