DKRd Regimen for Multiple Myeloma

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Disqualifiers: Frail, Amyloidosis, Plasma cell leukemia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 8 cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of four drugs—daratumumab, carfilzomib, lenalidomide, and dexamethasone—to evaluate their effectiveness in treating multiple myeloma, a cancer affecting plasma cells in the bone marrow. The goal is to assess patient responses after eight cycles of treatment. Newly diagnosed multiple myeloma patients who require chemotherapy might be suitable candidates, particularly if they have measurable disease markers like specific protein levels in blood or urine. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. However, it does mention that you should not have had certain treatments like radiotherapy or investigational drugs recently. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that the D-KRd regimen is likely to be safe for humans?

Research has shown that the combination of carfilzomib, daratumumab, and dexamethasone has been thoroughly studied in people with multiple myeloma. In earlier studies, patients generally tolerated carfilzomib and daratumumab well, both of which are approved for treating multiple myeloma. A large safety review of over 1,000 patients found that daratumumab, whether used alone or with other drugs, was generally safe.

The FDA has approved the combination of carfilzomib, daratumumab, and dexamethasone for patients whose multiple myeloma has returned or not responded to other treatments, indicating it meets safety standards for these patients. While side effects can occur, medical care usually manages them well.

Overall, this treatment plan has a well-documented safety record, which can reassure those considering joining clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Researchers are excited about the DKRd regimen for multiple myeloma because it combines four powerful treatments: Carfilzomib, Daratumumab, Dexamethasone, and Lenalidomide. Unlike the standard treatments which often involve just one or two of these drugs, this combination targets the cancer in multiple ways, potentially improving effectiveness. Carfilzomib and Daratumumab are particularly notable for their unique mechanisms; Carfilzomib is a proteasome inhibitor that disrupts protein breakdown in cancer cells, while Daratumumab is a monoclonal antibody that targets a specific protein on the surface of myeloma cells. Together, these drugs could offer a more comprehensive attack on the disease, giving patients a better chance at remission.

What evidence suggests that the D-KRd regimen could be effective for multiple myeloma?

Research has shown that the D-KRd regimen, which includes daratumumab, carfilzomib, lenalidomide, and dexamethasone, can effectively treat multiple myeloma. This blood cancer can return after treatment or not respond to it. In this trial, participants will receive the D-KRd regimen. Studies have found that this combination can lead to a good response in patients with relapsed or refractory multiple myeloma. The FDA has approved similar drug combinations for patients who have not responded to other treatments. Specifically, carfilzomib, when used with daratumumab and dexamethasone, showed promising results in improving patient outcomes. These findings suggest that the D-KRd regimen could be a strong option for those dealing with this challenging condition. ^{2 3 4 6 7}

Who Is on the Research Team?

Andrzej Jakubowiak, MD, PhD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for adults with newly diagnosed, untreated multiple myeloma who need systemic chemotherapy. They must have measurable disease, good performance status (able to carry out daily activities), and proper liver function. Women of childbearing age must use two forms of contraception or abstain from sex, and men must use condoms. Participants cannot join if they have certain heart conditions, severe lung problems like COPD or asthma, recent major surgery, active infections requiring treatment within the last two weeks, or a history of other cancers in the past three years.

Inclusion Criteria

You have a high level of protein in your urine.

I will provide a bone marrow sample for the study.

I am a woman who can have children and have had 2 negative pregnancy tests before starting lenalidomide.

Exclusion Criteria

I haven't had a heart attack in the last 6 months and don't have severe heart issues.

I have COPD with less than half the normal lung function.

I have been diagnosed with plasma cell leukemia.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 8 cycles of D-KRd (daratumumab, carfilzomib, lenalidomide, and dexamethasone) for multiple myeloma

8 cycles

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Daratumumab
• Dexamethasone
• Lenalidomide

Trial Overview The study tests a combination therapy called D-KRd: daratumumab (an antibody that targets cancer cells), carfilzomib (a drug that disrupts cancer cell waste disposal), lenalidomide (which affects the immune system and can kill cancer cells) and low dose dexamethasone (a steroid to reduce inflammation). The response rate after eight cycles will be measured to see how well this regimen works against multiple myeloma.

How Is the Trial Designed?

Group I: Treatment Arm (D-KRd) Experimental Treatment 4 Interventions

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?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Published Research Related to This Trial

In a phase 3 study involving 466 patients with relapsed or refractory multiple myeloma, the combination of carfilzomib, dexamethasone, and daratumumab (KdD) significantly improved progression-free survival compared to carfilzomib and dexamethasone alone (Kd), with a hazard ratio of 0.63, indicating a 37% reduction in the risk of disease progression.

Despite a higher incidence of grade 3 or higher adverse events in the KdD group (82%) compared to the Kd group (74%), the overall safety profile was considered favorable, with similar rates of treatment discontinuation due to adverse events in both groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Dimopoulos, M., Quach, H., Mateos, MV., et al.[2020]

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 the phase 3 CANDOR study involving 466 patients with relapsed or refractory multiple myeloma, the combination of carfilzomib, daratumumab, and dexamethasone (KdD) demonstrated a significantly longer median progression-free survival of 28.6 months compared to 15.2 months for carfilzomib and dexamethasone (Kd), indicating KdD's potential as a new standard-of-care treatment.

While KdD showed improved efficacy, it was associated with a higher incidence of grade 3 or worse treatment-emergent adverse events (87% in KdD vs. 76% in Kd), including thrombocytopenia and pneumonia, highlighting the need for careful monitoring of patients receiving this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): updated outcomes from a randomised, multicentre, open-label, phase 3 study. Usmani, SZ., Quach, H., Mateos, MV., et al.[2022]

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]

Isatuximab combined with carfilzomib and dexamethasone (Isa-Kd) demonstrated significantly better progression-free survival (PFS) compared to daratumumab combined with lenalidomide and dexamethasone (Dara-Rd) in patients with relapsed and/or refractory multiple myeloma, based on a matching-adjusted indirect comparison of 179 patients from the IKEMA trial and 286 patients from the POLLUX trial.

Patients receiving Isa-Kd experienced lower rates of treatment-emergent adverse events (TEAEs) compared to those on Dara-Rd, indicating a potentially safer profile for Isa-Kd in this treatment setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Matching-adjusted indirect comparison of isatuximab plus carfilzomib and dexamethasone with daratumumab plus lenalidomide and dexamethasone in relapsed multiple myeloma. Richter, J., Lin, PL., Garcia-Horton, V., et al.[2023]

Citations

1. amgen.com amgen.com/newsroom/press-releases/2021/12/fda-approves-new-kyprolis-carfilzomib-combination-regimen-with-darzalex-faspro-daratumumab-and-hyaluronidasefihj-and-dexamethasone-for-patients-with-multiple-myeloma-at-first-or-subsequent-relapse

FDA Approves New KYPROLIS® (carfilzomib ... The efficacy of KYPROLIS in combination with DARZALEX FASPRO and dexamethasone was evaluated in 66 patients with relapsed or refractory multiple ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9989580/

Daratumumab, carfilzomib, and dexamethasone in ... In conclusion, D-Kd continues to be well tolerated and effective in RRMM patients, including lenalidomide-refractory patients. Final analysis ...

3. bloodcancerunited.org bloodcancerunited.org/resources/newsroom/fda-approval-new-treatment-indication-multiple-myeloma-drug

New Treatment Indication for Multiple Myeloma Drug This is the sixth indication for daratumumab plus hyaluronidase in patients with multiple myeloma. It was first approved in 2015 and can be given alone or in ...

4. darzalexhcp.com darzalexhcp.com/indications-and-dosing/

Indications & Dosing DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with multiple myeloma: In combination with bortezomib, ...

5. fda.gov fda.gov/drugs/resources-information-approved-drugs/fda-approves-darzalex-faspro-kyprolis-and-dexamethasone-multiple-myeloma

FDA approves Darzalex Faspro, Kyprolis, and ... FDA approves Darzalex Faspro, Kyprolis, and Dexamethasone for Multiple Myeloma. ... The main efficacy outcome measure was overall response ...

6. kyprolis-hcp.com kyprolis-hcp.com/combinations/dkd-dosing

DKd Dosing | KYPROLIS® (carfilzomib) Learn more about dosing options and treatment schedules for KYPROLIS® (carfilzomib) + Darzalex® (daratumumab) + dexamethasone. See Full Safety Info.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/761145s009lbl.pdf

Darzalex Faspro - accessdata.fda.gov In a pooled safety population of 898 patients with multiple myeloma (N=705) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO as monotherapy ...