Daratumumab + KRd for Multiple Myeloma

Overseen By Ashley Franklin

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Wake Forest University Health Sciences

Must not be taking: Anti-CD-38 therapies

Disqualifiers: Infection, Pregnancy, Active malignancy, COPD, 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: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs to evaluate their effectiveness in treating multiple myeloma, a cancer affecting plasma cells in the bone marrow. The treatment includes daratumumab, which aids the immune system in attacking cancer cells, along with carfilzomib (also known as Kyprolis), lenalidomide, and dexamethasone. This trial targets individuals recently diagnosed with multiple myeloma who have not undergone more than one cycle of previous treatment. Those with a measurable level of the disease and limited prior therapy may qualify for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that you should not have more than one prior cycle of systemic therapy for multiple myeloma and any prior radiotherapy must be completed at least 14 days before starting the trial treatment.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that combining the drugs daratumumab, carfilzomib, lenalidomide, and dexamethasone is safe and manageable for patients with multiple myeloma. Studies found this drug mix effective and generally safe. Patients, including those who have tried other treatments, tolerated the treatment well. This suggests the combination can often be used without causing severe side effects. However, each patient's experience may vary, so discussing any concerns with a healthcare professional is important. ^{1 2 3 4 5}

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

Researchers are excited about the combination of Daratumumab with KRd (Carfilzomib, Lenalidomide, Dexamethasone) for treating multiple myeloma because it brings a fresh approach to tackling this cancer. Unlike standard treatments that often rely on separate use of these drugs, this combo uses Daratumumab, an antibody that targets a specific protein on myeloma cells, enhancing the immune system's ability to fight the cancer. Additionally, this combined regimen aims to improve patient outcomes by potentially offering a more powerful and comprehensive attack on the disease, which could lead to better responses than traditional therapies. This combination could change the game by improving the efficacy and possibly reducing the side effects associated with existing treatment methods.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that adding daratumumab to multiple myeloma (MM) treatment can greatly improve patient outcomes. Earlier studies have demonstrated that this combination leads to high rates of minimal residual disease (MRD) negativity, leaving behind very few cancer cells—a positive result. In this trial, participants will receive a combination of daratumumab with carfilzomib, lenalidomide, and dexamethasone. Previous studies indicated that patients who received daratumumab with other drugs had a 95% chance of living without their cancer worsening for four years. This combination effectively targets and destroys cancerous plasma cells in the bone marrow, suggesting a promising treatment option for those newly diagnosed with MM. ^{6 7 8 9 10}

Who Is on the Research Team?

Manisha Bhutani, MD

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for adults over 18 with newly diagnosed multiple myeloma. Participants must have good organ function, not be pregnant or breastfeeding, agree to use effective contraception methods, and cannot have had more than one prior treatment cycle for MM. They should not have severe lung conditions, recent major surgery, other active cancers or certain infections.

Inclusion Criteria

I have been active and mostly self-sufficient in the last 28 days.

I am committed to using two effective birth control methods.

Written informed consent and HIPAA authorization for release of personal health information signed by the subject or his/her legally authorized representative

Exclusion Criteria

I have another cancer that is growing or spreading.

I haven't used any experimental drugs or devices within the last 4 weeks.

I have had moderate to severe asthma in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Treatment

Participants receive induction therapy with carfilzomib, lenalidomide, dexamethasone, and daratumumab for 8 cycles

32 weeks

8 cycles (in-person)

Post-Induction Evaluation

Disease evaluation including assessment of minimal residual disease (MRD) to direct post-induction therapy

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

5 years

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Daratumumab
• Dexamethasone
• Lenalidomide

Trial Overview The study tests a combination of daratumumab with carfilzomib, lenalidomide and dexamethasone in new multiple myeloma cases. Daratumumab is an artificial protein that targets cancer cells and activates the immune system to fight them when combined with these medications.

How Is the Trial Designed?

Group I: KRd-Daratumumab Experimental Treatment 1 Intervention

Induction: Carfilzomib, lenalidomide, dexamethasone (KRd) + Daratumumab

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?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

Manisha Bhutani

Lead Sponsor

Trials

2

Recruited

50+

Saad Z. Usmani, MD

Lead Sponsor

Trials

5

Recruited

70+

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

Janssen, LP

Industry Sponsor

Trials

169

Recruited

329,000+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Mental Health Therapies

Top Products

Imodium, Remicade, Invega, Procrit

Joaquin Duato

Janssen, LP

Chief Executive Officer since 2022

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

Dr. Jijo James, MD

Janssen, LP

Chief Medical Officer since 2014

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

Celgene

Industry Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Published Research Related to This Trial

Daratumumab, a monoclonal antibody targeting CD38, has shown significant efficacy as a monotherapy in relapsed/refractory multiple myeloma, achieving an overall response in about one-third of patients, with rapid and durable effects.

In combination with other treatments like bortezomib or lenalidomide, daratumumab significantly prolonged progression-free survival, although the overall survival benefit is still being evaluated, and it was generally well tolerated with manageable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Relapsed and/or Refractory Multiple Myeloma. Blair, HA.[2018]

Daratumumab, when combined with lenalidomide and dexamethasone (DRd) or bortezomib and dexamethasone (DVd), showed an overall response rate of 80% in 171 heavily treated patients with relapsed/refractory multiple myeloma, indicating its efficacy in this challenging patient population.

Patients receiving the DRd combination experienced better progression-free survival (PFS) compared to those on DVd, with PFS rates of 84% and 77%, respectively, while the treatment was generally safe, with common side effects including neutropenia and infections.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab combined with dexamethasone and lenalidomide or bortezomib in relapsed/refractory multiple myeloma (RRMM) patients: Report from the multiple myeloma GIMEMA Lazio group. Fazio, F., Franceschini, L., Tomarchio, V., et al.[2022]

The combination of carfilzomib, pomalidomide, and dexamethasone (KPd) showed a high overall response rate of 79% in patients with relapsed/refractory multiple myeloma, indicating its efficacy as a treatment option.

Adding daratumumab to the KPd regimen (Dara-KPd) resulted in even better outcomes, with an overall response rate of 89% and a significant rate of measurable residual disease negativity, suggesting that Dara-KPd may provide deeper and more durable responses without compromising safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of carfilzomib, pomalidomide, and dexamethasone with and without daratumumab in relapsed multiple myeloma. Derman, BA., Zonder, J., Reece, D., et al.[2023]

Intravenous daratumumab, when combined with bortezomib, thalidomide, and dexamethasone, significantly improves treatment outcomes for adults with newly diagnosed multiple myeloma, leading to higher rates of stringent complete response and prolonged progression-free survival, as shown in the phase III CASSIOPEIA trial.

The addition of daratumumab has a minimal impact on overall toxicity, with the most common serious side effects being blood-related issues, indicating it is a relatively safe option for patients undergoing treatment for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. Lamb, YN.[2021]

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]

Intravenous daratumumab, when combined with bortezomib, melphalan, and prednisone, significantly improves progression-free survival in patients with newly diagnosed multiple myeloma who cannot undergo autologous stem cell transplantation, as shown in the phase 3 ALCYONE trial.

The addition of daratumumab does not increase overall toxicity compared to the standard treatment, although it may lead to more infusion-related reactions and infections, making it a promising and relatively safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Ineligible Newly Diagnosed Multiple Myeloma. Syed, YY.[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]

The combination therapy of daratumumab, carfilzomib, lenalidomide, and dexamethasone (D-KRd) was well tolerated in a study of 22 patients with newly diagnosed multiple myeloma, with a high overall response rate of 95%.

Most treatment-emergent adverse events were mild, with the most common being diarrhea and lymphopenia, and infusion-related reactions were primarily mild, indicating a favorable safety profile for D-KRd therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab Plus Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma. Jakubowiak, A., Usmani, SZ., Krishnan, A., et al.[2022]

Citations

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

New Treatment Indication for Multiple Myeloma Drug The most common adverse drug reactions in patients treated with daratumumab plus hyaluronidase were fatigue, pneumonia, upper respiratory tract infection and ...

2. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex/medical-content/use-of-darzalex-darzalex-faspro-in-combination-with-carfilzomib-lenalidomide-and-dexamethasone-in-m

DARZALEX® (daratumumab) A summary of clinical data regarding DARZALEX® (daratumumab) and DARZALEX FASPRO® (daratumumab and hyaluronidase) use in combination with ...

3. jnj.com jnj.com/media-center/press-releases/darzalex-faspro-daratumumab-and-hyaluronidase-fihj-based-regimen-shows-95-percent-progression-free-survival-at-four-years-in-transplant-eligible-newly-diagnosed-patients-with-multiple-myeloma-who-achieved-sustained-mrd-negativity

DARZALEX FASPRO® (daratumumab and hyaluronidase ... A DARZALEX FASPRO (daratumumab and hyaluronidase-fihj)-based quadruplet regimen demonstrated deep and sustained minimal residual disease (MRD) negativity rates.

4. darzalex.com darzalex.com/dvrd/

DARZALEX & DARZALEX FASPRO® (daratumumab and ... An FDA-approved treatment combination for patients who are newly diagnosed with multiple myeloma and eligible to receive a stem cell transplant.

5. cancer.gov cancer.gov/news-events/cancer-currents-blog/2024/multiple-myeloma-darzalex-plus-vrd

Daratumumab Plus Standard Therapy for Multiple Myeloma Adding daratumumab (Darzalex) to standard VRD treatment helped people with newly diagnosed multiple myeloma live longer without their cancer ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.7503

The ADVANCE clinical trial. In the current ADVANCE study (NCT04268498), patients were randomly assigned to receive 8 cycles of carfilzomib-lenalidomide-dexamethasone with ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10368773/

Final analysis of carfilzomib, dexamethasone, and ... Overall survival with daratumumab, lenalidomide, and dexamethasone in previously treated multiple myeloma (POLLUX): a randomized, open-label, phase III trial.

8. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2778195

Safety and Effectiveness of Weekly Carfilzomib ... This trial suggests that carfilzomib-lenalidomide-dexamethasone-daratumumab combination therapy may be safe and tolerable and is associated with high rates of ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2152265025001533

Original Study Real-World Use of carfilzomib-lenalidomide ... Carfilzomib administered as either KRd or Kd was effective and well tolerated, even in patients with multiple prior LOTs, confirming the safety and response ...

10. ashpublications.org ashpublications.org/blood/article/143/20/2029/515075/Daratumumab-carfilzomib-lenalidomide-and

Daratumumab, carfilzomib, lenalidomide, and dexamethasone ... High-risk (HR) cytogenetic abnormalities are associated with poor outcomes in patients with newly diagnosed multiple myeloma (NDMM).1,2 Risk ...