Carfilzomib + Iberdomide + Dexamethasone for Multiple Myeloma

Recruiting at 1 trial location

Overseen By Kristin Ivanovski

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Hackensack Meridian Health

Must not be taking: Immunosuppressants, CYP3A4/5 inducers

Disqualifiers: Nonsecretory MM, Plasma cell leukemia, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 cycles (28 days each)

66 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have taken certain treatments like strong inhibitors or inducers of CYP3A4/5, or immunosuppressive medications within 14 days before starting the trial. It's best to discuss your current medications with the study team.

What data supports the effectiveness of the drug combination Carfilzomib, Iberdomide, and Dexamethasone for treating multiple myeloma?

Carfilzomib combined with dexamethasone has shown promising activity in patients with relapsed or refractory multiple myeloma, and Iberdomide has demonstrated enhanced tumor-killing and immune-boosting effects in preclinical models when combined with dexamethasone. ^{1 2 3 4 5}

Is the combination of Carfilzomib, Iberdomide, and Dexamethasone safe for humans?

Carfilzomib and dexamethasone have been studied together and shown to have a safety profile with mostly low-grade side effects, though some serious heart-related issues were noted in a small percentage of patients. The combination of Carfilzomib with other drugs like lenalidomide has been well tolerated in studies, but specific safety data for Iberdomide in this combination is not available. ^{1 4 5 6 7}

What makes the drug combination of Carfilzomib, Iberdomide, and Dexamethasone unique for treating multiple myeloma?

The combination of Carfilzomib, Iberdomide, and Dexamethasone is unique because it combines a proteasome inhibitor (Carfilzomib), an immunomodulatory drug (Iberdomide), and a corticosteroid (Dexamethasone) to target multiple pathways in multiple myeloma, potentially offering a more comprehensive approach than treatments using single agents. ^{8 9 10 11 12}

Research Team

Noa Biran, MD

Principal Investigator

Hackensack Meridian Health

Eligibility Criteria

This trial is for adults over 18 with newly diagnosed multiple myeloma who are eligible for a transplant. They must have measurable disease, be in good enough health to participate (ECOG score of 0-2), and agree to contraception or abstinence. High-risk patients should make up at least a quarter of participants. Those with severe medical conditions, prior malignancies within five years (except certain noninvasive ones), serious heart issues, uncontrolled diabetes or hypertension, HIV, active hepatitis, or significant neuropathy cannot join.

Inclusion Criteria

Either commit to true abstinence from heterosexual contact or agree to use two forms of contraception

I have been diagnosed with multiple myeloma and it can be measured.

I am a male and will either not have sex or use a condom with women who can get pregnant.

Exclusion Criteria

I am not pregnant, nursing, or planning to become pregnant, and I agree to follow the study's contraceptive and pregnancy monitoring requirements.

I do not have severe kidney issues or nerve damage.

I have been cancer-free for over 5 years, except for certain non-invasive cancers.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Initial dose escalation phase with Iberdomide, Carfilzomib, and Dexamethasone to determine safety and tolerability

2 months

Multiple visits for safety assessments

Treatment

Participants receive up to 4 cycles of treatment with Carfilzomib, Iberdomide, and Dexamethasone followed by Autologous Stem Cell Transplant

4 cycles (28 days each)

Weekly visits during each cycle

Follow-up

Participants are monitored every 3 months for up to 2 years for safety and effectiveness after treatment

Up to 2 years

Quarterly visits

Treatment Details

Interventions

• Carfilzomib
• Dexamethasone
• Iberdomide

Trial Overview The study tests a combination therapy called KID—Carfilzomib (an intravenous drug), Iberdomide (a pill), and Dexamethasone (also oral)—on people with new multiple myeloma who can get transplants. It's an open-label phase I/II trial which means everyone knows what treatment they're getting and it aims to find the right dose and see how well it works.

Participant Groups

Group I: Starting Dose -1 Experimental Treatment 3 Interventions

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.

Group II: Dose Level 2 Experimental Treatment 3 Interventions

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.

Group III: Dose Level 1 Experimental Treatment 3 Interventions

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.

Group IV: Dose Level -2 Experimental Treatment 3 Interventions

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.

Carfilzomib is already approved in United States, European Union, Canada, Japan for the following indications:

Approved in United States as Kyprolis for:

• Multiple myeloma

Approved in European Union as Kyprolis for:

• Multiple myeloma

Approved in Canada as Kyprolis for:

• Multiple myeloma

Approved in Japan as Kyprolis for:

• Multiple myeloma

Who Is Running the Clinical Trial?

Hackensack Meridian Health

Lead Sponsor

Trials

141

Recruited

42,900+

Findings from Research

The KRd regimen (carfilzomib, lenalidomide, and dexamethasone) demonstrated a high overall response rate of 88.5% in 26 heavily pretreated Japanese patients with relapsed or refractory multiple myeloma, indicating its efficacy in this challenging patient population.

While the KRd regimen was generally well tolerated, a higher incidence of hyperglycemia was noted, likely due to dexamethasone, suggesting the need for monitoring blood sugar levels during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, lenalidomide and dexamethasone in patients with heavily pretreated multiple myeloma: A phase 1 study in Japan. Suzuki, K., Ri, M., Chou, T., et al.[2021]

In a real-world study of 152 patients with relapsed and/or refractory multiple myeloma treated with carfilzomib plus dexamethasone, the overall response rate was 71.1%, indicating that this treatment is effective in a clinical setting.

Patients classified as trial-unfit had significantly shorter progression-free survival (3.6 months) and overall survival (15.0 months) compared to trial-fit patients (7.3 months and 36.8 months, respectively), highlighting the importance of patient fitness in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world treatment outcomes of carfilzomib plus dexamethasone in patients with relapsed and/or refractory multiple myeloma, focusing on the impact of trial-fitness: CAtholic REsearch network for Multiple Myeloma study (CAREMM-2203). Park, SS., Goo, SY., Jeon, YW., et al.[2023]

Iberdomide combined with dexamethasone demonstrated meaningful clinical activity in heavily pretreated patients with relapsed or refractory multiple myeloma, achieving an overall response rate of 32% in the dose-escalation cohort and 26% in the dose-expansion cohort, indicating its potential effectiveness even in difficult-to-treat cases.

The treatment was generally safe, with a recommended phase 2 dose established at 1.6 mg, although some patients experienced serious adverse events, including neutropenia and infections, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. Lonial, S., Popat, R., Hulin, C., et al.[2022]

In the ENDURANCE trial involving patients with newly diagnosed multiple myeloma, the combination of carfilzomib, lenalidomide, and dexamethasone (KRd) did not improve progression-free survival compared to the standard treatment of bortezomib, lenalidomide, and dexamethasone (VRd).

These findings suggest that KRd may not be a more effective treatment option than the current standard of care for patients with NDMM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib Triplet Fails to Induce Superior PFS in Newly Diagnosed Multiple Myeloma. Skarzynski, J.[2021]

In a study involving 929 patients with relapsed or refractory multiple myeloma, carfilzomib combined with dexamethasone significantly improved median progression-free survival (18.7 months) compared to bortezomib with dexamethasone (9.4 months), indicating greater efficacy of carfilzomib.

While both treatments had serious adverse events, carfilzomib was associated with a higher rate of serious adverse events (48%) compared to bortezomib (36%), suggesting that while carfilzomib may be more effective, it also carries a higher risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Dimopoulos, MA., Moreau, P., Palumbo, A., et al.[2022]

In a phase 2 study involving 72 patients with newly diagnosed multiple myeloma, the combination of carfilzomib and dexamethasone (Kd) achieved a remarkable overall response rate of 90%, with 7% of patients reaching a complete response and 58% achieving a very good partial response.

The treatment was generally well-tolerated, with most adverse events being low grade; however, there was an 11.1% incidence of grade 3 or higher cardiovascular events, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of carfilzomib and dexamethasone therapy for newly diagnosed multiple myeloma. Forsberg, PA., Rossi, AC., Boyer, A., et al.[2020]

Carfilzomib, when used in combination with lenalidomide and dexamethasone, significantly prolongs progression-free survival (PFS) by 8.7 months in patients with relapsed multiple myeloma, based on results from the phase III ASPIRE study involving a multinational patient population.

The combination therapy has a manageable safety profile, with low incidences of severe adverse events, suggesting it is a viable treatment option for patients who have received prior therapies, although overall survival data is still pending.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib Triple Combination Therapy: A Review in Relapsed Multiple Myeloma. Hoy, SM.[2018]

FK-037 demonstrated strong antibacterial activity against 90% of Enterobacteriaceae isolates at very low concentrations (≤ 0.25 microgram/ml), making it a promising option for treating infections caused by these bacteria.

In comparison to other beta-lactam antibiotics, FK-037 was particularly effective against resistant strains, showing 8- to 16-fold greater activity than cefotaxime and ceftazidime, and comparable efficacy to cefpirome and cefepime against certain resistant strains of Klebsiella pneumoniae.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multicentre comparative study on the antibacterial activity of FK-037, a new parenteral cephalosporin. Martínez-Beltrán, J., Cantón, R., Liñares, J., et al.[2023]

In a study involving 253 bacterial isolates from cancer patients, three new antimicrobial agents (cefpirome, BMY 28142, WIN 49375) and imipenem showed significantly greater effectiveness compared to four currently available antibiotics (ceftazidime, aztreonam, timentin, and piperacillin).

The findings suggest that these new agents may offer improved treatment options for infections in cancer patients, highlighting their potential efficacy in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In-vitro activity of cefpirome (HR-810), WIN-49375, BMY-28142 and other antibiotics against nosocomially important isolates from cancer patients. Rolston, KV., Alvarez, ME., Hsu, KC., et al.[2023]

FK037, a new cephalosporin antibiotic, demonstrated superior in vitro antimicrobial activity against various bacteria, including Pseudomonas aeruginosa and Staphylococcus aureus, compared to existing antibiotics like ceftazidime and cefepime.

In animal models, FK037 showed strong efficacy against systemic infections and specific conditions like pyelonephritis and pneumonia, indicating its potential as a powerful treatment option for serious bacterial infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro and in vivo antibacterial activities of FK037, a novel parenteral broad-spectrum cephalosporin. Fu, KP., Foleno, BD., Lafredo, SC., et al.[2021]

Cefpirome demonstrated strong bactericidal activity against both Haemophilus influenzae type b and Escherichia coli K1 in a rabbit model of meningitis, with significant reductions in bacterial concentrations in the cerebrospinal fluid (CSF) compared to untreated groups.

The drug achieved mean CSF penetration rates of 25% for H. influenzae and 54% for E. coli, and its effectiveness was not compromised by the prior administration of dexamethasone, indicating its potential as a safe and effective treatment for bacterial meningitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and antibacterial efficacy of cefpirome (HR 810) in experimental Escherichia coli and Haemophilus influenzae type b meningitis. Jafari, HS., Sáez-Llorens, X., Ramilo, O., et al.[2023]

FK-037, a new cephalosporin antibiotic, demonstrated superior in vitro activity compared to ceftazidime, aztreonam, and piperacillin against various bacterial isolates from cancer patients, being 2 to 16 times more effective against Enterobacteriaceae.

FK-037 showed significant effectiveness against many gram-positive bacteria, including some methicillin-resistant staphylococci, indicating its potential as a broad-spectrum antimicrobial agent, although some organisms like Enterococcus spp. were resistant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vitro activity of FK-037, a novel parenteral cephalosporin, against bacterial isolates from neutropenic cancer patients. Dholakia, N., Rolston, KV., Ho, DH., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

Carfilzomib, lenalidomide and dexamethasone in patients with heavily pretreated multiple myeloma: A phase 1 study in Japan. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Real-world treatment outcomes of carfilzomib plus dexamethasone in patients with relapsed and/or refractory multiple myeloma, focusing on the impact of trial-fitness: CAtholic REsearch network for Multiple Myeloma study (CAREMM-2203). [2023]

3. England pubmed.ncbi.nlm.nih.gov

Iberdomide plus dexamethasone in heavily pretreated late-line relapsed or refractory multiple myeloma (CC-220-MM-001): a multicentre, multicohort, open-label, phase 1/2 trial. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Carfilzomib Triplet Fails to Induce Superior PFS in Newly Diagnosed Multiple Myeloma. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Phase II study of carfilzomib and dexamethasone therapy for newly diagnosed multiple myeloma. [2020]

7. France pubmed.ncbi.nlm.nih.gov

Carfilzomib Triple Combination Therapy: A Review in Relapsed Multiple Myeloma. [2018]

8. Germany pubmed.ncbi.nlm.nih.gov

Multicentre comparative study on the antibacterial activity of FK-037, a new parenteral cephalosporin. [2023]

9. England pubmed.ncbi.nlm.nih.gov

In-vitro activity of cefpirome (HR-810), WIN-49375, BMY-28142 and other antibiotics against nosocomially important isolates from cancer patients. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

In vitro and in vivo antibacterial activities of FK037, a novel parenteral broad-spectrum cephalosporin. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and antibacterial efficacy of cefpirome (HR 810) in experimental Escherichia coli and Haemophilus influenzae type b meningitis. [2023]

12. Germany pubmed.ncbi.nlm.nih.gov

In vitro activity of FK-037, a novel parenteral cephalosporin, against bacterial isolates from neutropenic cancer patients. [2019]