Combination Chemotherapy for Multiple Myeloma

Recruiting at 2 trial locations

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Must not be taking: Concurrent chemotherapy

Disqualifiers: HIV, Hepatitis B, Hepatitis C, 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: 7

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of four chemotherapy drugs to determine if they can improve blood test results for individuals with high-risk multiple myeloma, a type of blood cancer. The drugs employ different methods to halt the growth and spread of cancer cells. Participants with a small amount of cancer remaining after the first treatment may benefit significantly. Suitable candidates have untreated high-risk multiple myeloma and specific genetic markers or symptoms, such as more than 5% circulating plasma cells. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take other chemotherapy treatments not related to multiple myeloma while participating in this trial.

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

Research shows that the combination of carfilzomib, daratumumab, lenalidomide, and dexamethasone has been tested in patients with multiple myeloma, particularly those whose cancer has returned after treatment. In these studies, common side effects include fatigue, pneumonia, and upper respiratory infections like a cold.

The FDA has approved this combination for certain cases of multiple myeloma, indicating it is generally safe for use. A review of 1,249 patients found that the treatment had side effects that could usually be managed, meaning they can often be treated or controlled.

While these findings support the combination's safety, each person's experience can differ. Always consult a healthcare provider about potential risks and benefits before joining a clinical trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment combination for multiple myeloma because it brings together four powerful drugs: Carfilzomib, Daratumumab, Dexamethasone, and Lenalidomide. This combo targets the cancer in multiple ways, potentially leading to better outcomes. Carfilzomib is a proteasome inhibitor that disrupts cancer cell growth, while Daratumumab, a monoclonal antibody, directly targets myeloma cells. Lenalidomide and Dexamethasone further enhance the immune response against the cancer. This multi-pronged approach could offer a more robust treatment option compared to standard regimens, which often use fewer drugs with narrower mechanisms of action.

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

Research shows that a combination of four drugs—carfilzomib, daratumumab, lenalidomide, and dexamethasone—effectively treats multiple myeloma, a type of blood cancer. In this trial, participants will receive this combination as part of the treatment regimen. Studies have found that this combination improves the condition of patients whose cancer has returned or is not responding to other treatments, slowing the disease's progression. This drug mix has received approval for use in certain situations, highlighting its potential effectiveness. Overall, this combination has shown promise in helping patients manage their multiple myeloma. ^{2 3 4 5 6}

Who Is on the Research Team?

Shaji K. Kumar, MD

Principal Investigator

Mayo Clinic in Rochester

Are You a Good Fit for This Trial?

Adults aged 18-80 with newly diagnosed high-risk multiple myeloma, able to perform daily activities (ECOG PS 0 or 1), and have not had significant treatment yet. Participants must be willing to provide samples for research, take daily aspirin, and have a life expectancy over 6 months. They should not have severe allergies to trial drugs or their components, major surgery within the last two weeks, other serious medical conditions that could affect participation, or be pregnant/nursing without using contraception.

Inclusion Criteria

Your total bilirubin level needs to be within a certain range, as measured within the last 14 days before joining the study.

Your heart's pumping ability (LVEF) should be between 40% and 30% within the last 30 days before pre-registration.

My kidney function, measured by creatinine clearance, is adequate.

Exclusion Criteria

I am HIV positive.

I have not had major surgery in the last 14 days.

I have heart failure that affects my daily activities.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Patients receive carfilzomib, lenalidomide, daratumumab, and dexamethasone. Treatment repeats every 28 days for 12 cycles.

48 weeks

Multiple visits per cycle

Consolidation

Patients continue receiving carfilzomib, lenalidomide, and daratumumab. Treatment repeats every 28 days for 12 cycles.

48 weeks

Multiple visits per cycle

Maintenance

Patients receive carfilzomib, lenalidomide, and daratumumab. Treatment repeats every 28 days for 12 cycles.

48 weeks

Multiple visits per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

Up to 10 years

Every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Daratumumab
• Dexamethasone
• Lenalidomide

Trial Overview The REACH Trial is testing if a combination of chemotherapy drugs—carfilzomib, daratumumab, lenalidomide, and dexamethasone—can improve blood test results in patients with high-risk multiple myeloma after initial treatment has left minimal residual disease. The study includes imaging tests like CT scans and MRIs to monitor cancer progression.

How Is the Trial Designed?

Group I: Treatment (combination chemotherapy) Experimental Treatment 12 Interventions

INDUCTION: Patients receive carfilzomib IV on days 2, 8, and 15 of cycle 1 and days 1, 8, and 15 of cycles 2-12, lenalidomide PO days 1-21 of each cycle, daratumumab SC days 1, 8, 15, and 22 of cycles 1 and 2, days 1 and 15 of cycles 3-6, and day 1 of subsequent cycles, and dexamethasone PO or IV on days 1, 8, 15, and 22 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients receive carfilzomib IV on days 1, 8, and 15, lenalidomide PO days 1-21, daratumumab SC day 1 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. MAINTENANCE: Patients receive carfilzomib IV on day 1, lenalidomide PO days 1-21, daratumumab day 1 of each cycle. Treatment repeats every 28 days for 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo bone marrow aspirate and biopsy, MRI and, CT/PET.

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?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

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]

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]

In a study involving 792 patients with relapsed multiple myeloma, the combination of carfilzomib with lenalidomide and dexamethasone significantly improved progression-free survival, with a median of 26.3 months compared to 17.6 months for the control group.

The carfilzomib group also showed a higher overall response rate (87.1% vs. 66.7%) and better health-related quality of life, indicating a favorable risk-benefit profile despite similar rates of serious adverse events between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. Stewart, AK., Rajkumar, SV., Dimopoulos, MA., 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 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]

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. 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. 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 ...

3. 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 ...

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

Daratumumab, carfilzomib, and dexamethasone in ... Overall, D-Kd demonstrated efficacy in PLEIADES, EQUULEUS, and CANDOR, supporting its use for RRMM, including lenalidomide-refractory multiple ...

5. 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, ...

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 ...