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

Trial Summary

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.

What data supports the effectiveness of the drug combination Carfilzomib, Kyprolis, Daratumumab, Darzalex, Darzalex SC, Darzalex Faspro, Dexamethasone, Decadron, Dexone, Hexadrol, Lenalidomide, Revlimid for treating multiple myeloma?

Research shows that the combination of carfilzomib, dexamethasone, and daratumumab is effective for patients with relapsed or refractory multiple myeloma, with studies demonstrating substantial efficacy and tolerable safety. Additionally, carfilzomib combined with lenalidomide and dexamethasone has been shown to significantly prolong progression-free survival in patients who have received prior therapy. ^{1 2 3 4 5}

Is the combination chemotherapy for multiple myeloma safe for humans?

The combination of carfilzomib, dexamethasone, and daratumumab has shown tolerable safety in patients with relapsed or refractory multiple myeloma. Carfilzomib combined with lenalidomide and dexamethasone also has a manageable safety profile, with low incidences of severe side effects, making it a viable treatment option for multiple myeloma. ^{2 3 4 6 7}

What makes the combination chemotherapy for multiple myeloma unique?

This treatment combines carfilzomib, daratumumab, dexamethasone, and lenalidomide, which includes a proteasome inhibitor (carfilzomib) and an immunotherapy drug (daratumumab) that work together to target cancer cells in different ways, potentially offering a more effective option for patients with relapsed or refractory multiple myeloma. ^{2 3 4 6 7}

What is the purpose of this trial?

This phase II trial test whether combination chemotherapy works to improve blood test results in patients with high-risk multiple myeloma. Chemotherapy drugs, such as carfilzomib, daratumumab, lenalidomide, and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. This trial may help determine if patients who have a small amount of cancer left after the initial treatment, called minimal residual disease, will benefit from the drug combination.

Research Team

Shaji K. Kumar, MD

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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 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]

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]

References

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

Carfilzomib in combination with daratumumab in the management of relapsed multiple myeloma. [2021]

2. England 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. [2020]

3. France pubmed.ncbi.nlm.nih.gov

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

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

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

5. United States 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. [2023]

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

Daratumumab Plus Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Newly Diagnosed Multiple Myeloma. [2022]

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

Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. [2022]