Daratumumab Combination Therapy for Multiple Myeloma

Not currently recruiting at 7 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Disqualifiers: Plasma cell leukemia, POEMS, Amyloidosis, 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: Unknown

Duration: 8 cycles

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the safety and effectiveness of a combination of four drugs—daratumumab, carfilzomib, lenalidomide, and dexamethasone—for treating multiple myeloma, a type of blood cancer. The researchers aim to understand how these drugs work together to benefit newly diagnosed patients. Individuals recently diagnosed with multiple myeloma, who exhibit certain signs of the disease, such as abnormal proteins in their blood or urine, might be suitable candidates for this trial. 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, if you have been treated for smoldering myeloma, a 2-week period without treatment is required before joining the trial. Some medications like corticosteroids and bisphosphonates are allowed.

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

Research has shown that the combination of four drugs—daratumumab, carfilzomib, lenalidomide, and dexamethasone—is generally safe for patients with multiple myeloma, a type of cancer. This treatment has proven effective, with most patients experiencing no serious problems.

Earlier studies identified common side effects such as tiredness and infections like pneumonia and colds. However, medical care can usually manage these side effects. The FDA has approved this combination for treating certain types of multiple myeloma, indicating confidence in its safety. While the study aims to further confirm its safety, current evidence is encouraging for those considering joining the trial. ^{1 2 3 4 5}

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

Researchers are excited about this combination therapy for multiple myeloma because it brings together four powerful drugs: daratumumab, carfilzomib, lenalidomide, and dexamethasone. Unlike standard treatments, which often use these drugs individually or in smaller combinations, this regimen harnesses the synergistic effects of all four. Daratumumab is especially noteworthy because it is a monoclonal antibody that targets CD38, a protein highly expressed on myeloma cells, enhancing the immune system's ability to attack these cells. By integrating these targeted therapies, the combination aims to improve patient outcomes more effectively than existing treatments alone.

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

Research has shown that a combination of four drugs—daratumumab, carfilzomib, lenalidomide, and dexamethasone—holds promise for treating multiple myeloma. Participants in this trial will receive this combination therapy. Studies have found that it can significantly reduce the number of cancer cells in the body. In some studies, up to 85% of patients had very few cancer cells remaining, indicating strong treatment efficacy. This combination has also been linked to longer periods without cancer progression. This evidence suggests that the treatment could be effective for newly diagnosed multiple myeloma patients. ^{2 4 6 7 8}

Who Is on the Research Team?

Neha Korde, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

This trial is for newly diagnosed multiple myeloma patients with measurable disease, specific organ damage, and certain blood and liver function levels. Participants must not have had more than one cycle of prior treatment. Women who can bear children and men must follow strict birth control rules.

Inclusion Criteria

I am using birth control and have had a recent negative pregnancy test.

My health status meets specific criteria related to blood, bone, kidney, liver conditions, and my physical ability.

You have a specific type of disease that has been measured within the past 4 weeks using specific tests for proteins in the blood and urine, as well as any related organ damage.

Exclusion Criteria

I do not have specific conditions like uncontrolled diabetes, heart disease, or recent major surgery.

I have received more than one cycle of treatment for multiple myeloma.

I have followed the required break period after my last treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive combination therapy with daratumumab, carfilzomib, lenalidomide, and dexamethasone. Patients achieving ≥PR at the end of 4 cycles will continue to receive a total of 8 cycles.

8 cycles

Maintenance

Patients may receive additional maintenance therapy with lenalidomide under a separate treatment protocol.

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on assessing MRD negativity.

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Daratumumab
• Dexamethasone
• Lenalidomide

Trial Overview The study tests the safety and effectiveness of daratumumab combined with carfilzomib, lenalidomide, and dexamethasone in treating multiple myeloma. The goal is to determine if this drug mix is safe for patients.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 4 Interventions

Single arm, two-stage phase II trial of combination therapy (daratumumab, carfilzomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma patients. Patients achieving ≥PR at end of 4 cycles will continue to receive the planned total of 8 cycles of combination therapy. Patients may go onto receiving additional maintenance phase therapy with lenalidomide under a separate treatment protocol. Patients ≤ PR after completing 4 cycles will go off study therapy.

Group II: Cohort 1 Experimental Treatment 4 Interventions

Single arm, two-stage phase II trial of combination therapy (daratumumab, carfilzomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma patients. Patients achieving ≥PR at end of 4 cycles will continue to receive the planned total of 8 cycles of combination therapy. Patients may go onto receiving additional maintenance phase therapy with lenalidomide under a separate treatment protocol. Patients ≤ PR after completing 4 cycles will go off study 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?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Janssen Pharmaceuticals

Industry Sponsor

Trials

87

Recruited

208,000+

Joaquin Duato

Janssen Pharmaceuticals

Chief Executive Officer since 2022

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

Dr. Jijo James, MD

Janssen Pharmaceuticals

Chief Medical Officer since 2014

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

Published Research Related to This Trial

The combination of daratumumab, carfilzomib, and dexamethasone has shown strong clinical efficacy in treating relapsed multiple myeloma, particularly in patients whose disease is refractory to lenalidomide.

This triplet therapy has been approved by the US FDA for use in relapsed multiple myeloma, highlighting its significance as a treatment option in a setting with limited effective alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib in combination with daratumumab in the management of relapsed multiple myeloma. Touzeau, C., Antier, C., Moreau, P.[2021]

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]

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]

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]

The combination therapy of carfilzomib, lenalidomide, dexamethasone, and daratumumab achieved a high minimal residual disease (MRD) negativity rate of 71% in newly diagnosed multiple myeloma patients, indicating effective treatment without the need for high-dose melphalan chemotherapy or autologous transplant.

The treatment demonstrated excellent safety and tolerability, with a 1-year progression-free survival rate of 98% and no reported deaths, although some patients experienced grade 3 or 4 adverse events like neutropenia and rash.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Effectiveness of Weekly Carfilzomib, Lenalidomide, Dexamethasone, and Daratumumab Combination Therapy for Patients With Newly Diagnosed Multiple Myeloma: The MANHATTAN Nonrandomized Clinical Trial. Landgren, O., Hultcrantz, M., Diamond, B., et al.[2022]

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, 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]

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 is a monoclonal antibody that effectively targets CD38 on multiple myeloma cells, leading to cell death through various mechanisms such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

It has shown a favorable safety profile and significant clinical activity as both a standalone treatment and in combination with lenalidomide for patients with relapsed multiple myeloma who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. Xia, C., Ribeiro, M., Scott, S., et al.[2018]

Citations

1. darzalex.com darzalex.com/

Official Consumer Website | DARZALEX® & DARZALEX ... DARZALEX FASPRO® is a prescription medicine used to treat adult patients with multiple myeloma: in combination with the medicines bortezomib, lenalidomide, and ...

2. 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 ...

3. 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 ...

4. jnj.com jnj.com/media-center/press-releases/darzalex-faspro-daratumumab-and-hyaluronidase-fihj-based-regimens-demonstrate-improved-rates-of-minimal-residual-disease-mrd-negativity-and-progression-free-survival-in-patients-with-newly-diagnosed-multiple-myeloma

DARZALEX FASPRO® (daratumumab and hyaluronidase ... New analysis from Phase 3 CEPHEUS study demonstrates 85 percent of patients who achieved MRD negativity (10-6) with DARZALEX FASPRO® were ...

5. aetna.com aetna.com/cpb/medical/data/900_999/0904.html?ref=counterforcehealth.org

Daratumumab (Darzalex) and Daratumumab and ... Darzalex Faspro is indicated for the treatment of adult patients with multiple myeloma: in combination with bortezomib, lenalidomide, and dexamethasone for ...

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

FDA approves Darzalex Faspro, Kyprolis, and ... This cohort enrolled 66 patients with relapsed or refractory multiple myeloma who received at least one prior line of therapy. Patients received ...

7. 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.

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

Daratumumab, carfilzomib, and dexamethasone in ... Daratumumab, carfilzomib, and dexamethasone in relapsed or refractory myeloma: final analysis of PLEIADES and EQUULEUS