Carfilzomib + Pomalidomide + Dexamethasone + Daratumumab for Multiple Myeloma

No longer recruiting at 4 trial locations

Overseen By Cancer Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Chicago

Must be taking: Lenalidomide

Must not be taking: Antibiotics, Antivirals, Antifungals

Disqualifiers: Stem cell transplant, Plasma cell leukemia, Waldenström's macroglobulinemia, Uncontrolled hypertension, Diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Variable (until disease progression or unacceptable toxicity)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores new combinations of medications to treat multiple myeloma, a type of blood cancer that can recur or resist treatment. Researchers aim to determine if adding daratumumab (Darzalex) to a regimen of carfilzomib (Kyprolis), pomalidomide (Pomalyst), and dexamethasone enhances treatment effectiveness. The trial seeks participants whose multiple myeloma has returned or not responded after at least one treatment, particularly if lenalidomide was ineffective. Participants should be able to manage daily activities without major health issues. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new combination therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you should not have received any anti-cancer therapy within 21 days of enrollment, which might imply a need to pause certain treatments. Please consult with the trial coordinators for specific guidance.

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

Research has shown that the combination of carfilzomib, pomalidomide, and dexamethasone is generally well-tolerated by patients with relapsed or hard-to-treat multiple myeloma. Studies have found this treatment beneficial, with most patients managing any side effects.

When daratumumab is added, research suggests it remains safe and effective. Some studies note a few additional blood-related side effects with this combination, but overall, it remains a good option for patients. In both cases, the treatments help control the disease while keeping side effects manageable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for multiple myeloma because they combine powerful drugs in a novel way to enhance effectiveness. Carfilzomib, pomalidomide, and dexamethasone are well-known for their ability to target cancer cells, but adding daratumumab—a monoclonal antibody that specifically attacks myeloma cells—can potentiate this effect. Unlike standard treatments that use these drugs separately, this combination aims to maximize cancer cell destruction while potentially minimizing side effects and resistance. By integrating these agents, this approach may provide a more comprehensive attack on the disease, offering hope for improved outcomes.

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

In this trial, participants will receive one of two treatment combinations. Studies have shown that the combination of carfilzomib, pomalidomide, and dexamethasone can be effective for patients with relapsed or refractory multiple myeloma. Earlier research demonstrated that this combination improved patient outcomes by targeting and killing cancer cells. Another group in this trial will receive this combination plus an additional drug, daratumumab. Research indicates that adding daratumumab can enhance the treatment's effectiveness. These medicines work together to attack cancer cells in different ways, offering hope for better disease control. ^{2 4 5 6 7}

Who Is on the Research Team?

Andrzej Jakubowiak, MD, PhD

Principal Investigator

University of Chicago Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with relapsed or refractory multiple myeloma who've had at least one prior treatment and are not planning a stem cell transplant soon. They must have measurable disease, be able to follow the study plan, use birth control, and have good liver function and blood counts. People can't join if they've had recent cancer treatments, heart issues, certain other cancers within 3 years, uncontrolled conditions like hypertension or diabetes, active infections requiring drugs, HIV/AIDS, significant neuropathy or allergies to related drugs.

Inclusion Criteria

Must agree to practice abstinence or use two acceptable methods of birth control

Written informed consent

Must agree to adhere to all study requirements, visit schedule, outpatient treatment, required concomitant medications, and laboratory monitoring

Exclusion Criteria

Pregnant or lactating

You have had an allergic reaction to mannitol, thalidomide, lenalidomide, or pomalidomide in the past.

I have been diagnosed with POEMS syndrome.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive carfilzomib, pomalidomide, and dexamethasone in 28-day treatment cycles. Treatment continues as long as the myeloma does not worsen and there are no unacceptable side effects.

Variable (until disease progression or unacceptable toxicity)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Daratumumab
• Dexamethasone
• Pomalidomide

Trial Overview

The study tests adding carfilzomib to pomalidomide and dexamethasone in patients with multiple myeloma that has come back or didn't respond to treatment. It also looks at the effects of including daratumumab in this combination therapy. The trial involves increasing doses of these drugs to find out how well they work together.

How Is the Trial Designed?

Group I: PdC Group Experimental Treatment 3 Interventions

Patients receive carfilzomib, pomalidomide, and dexamethasone at indicated doses and schedule every 28 days. Patients may continue to receive treatment in the absence of disease progression or unacceptable toxicity.

Group II: PdC + Dara Group Experimental Treatment 4 Interventions

Patients receive carfilzomib, pomalidomide, dexamethasone, and daratumumab at indicated doses and schedule every 28 days. Patients may continue to receive treatment in the absence of disease progression or unacceptable toxicity.

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+

Multiple Myeloma Research Foundation

Collaborator

Trials

11

Recruited

3,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Pomalidomide, combined with low-dose dexamethasone, has been shown to be effective in treating adult patients with relapsed and refractory multiple myeloma, significantly improving progression-free survival and overall response rates compared to high-dose dexamethasone.

The treatment demonstrated a manageable safety profile and was effective across various patient subgroups, including those who were refractory to previous therapies, indicating its potential as a valuable salvage therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. Scott, LJ.[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]

Pomalidomide, when combined with low-dose dexamethasone, significantly improves progression-free survival and overall survival in adults with relapsed and refractory multiple myeloma, based on results from multinational phase II and III studies involving patients who had undergone at least two prior treatments.

The treatment has a manageable safety profile, with the most common serious side effects being neutropenia, infections, anemia, and thrombocytopenia, making it a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. Hoy, SM.[2018]

The novel combination therapy of carfilzomib, pomalidomide, and dexamethasone (CPD) was found to be well-tolerated and highly active in treating patients with relapsed and refractory multiple myeloma, with a total of 32 patients enrolled in the study.

The maximum tolerated dose (MTD) was established at carfilzomib 20/27 mg/m², pomalidomide 4 mg, and dexamethasone 40 mg, although hematologic adverse events were common, affecting over 60% of patients, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Shah, JJ., Stadtmauer, EA., Abonour, R., et al.[2022]

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 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 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]

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 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 2 study involving 72 patients with newly diagnosed multiple myeloma, the combination of carfilzomib and dexamethasone (Kd) achieved a remarkable overall response rate of 90%, with 7% of patients reaching a complete response and 58% achieving a very good partial response.

The treatment was generally well-tolerated, with most adverse events being low grade; however, there was an 11.1% incidence of grade 3 or higher cardiovascular events, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of carfilzomib and dexamethasone therapy for newly diagnosed multiple myeloma. Forsberg, PA., Rossi, AC., Boyer, A., et al.[2020]

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