Carfilzomib + Lenalidomide + Dexamethasone with Stem Cell Transplant for Multiple Myeloma

Not currently recruiting at 5 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Chicago

Must be taking: Carfilzomib, Lenalidomide, Dexamethasone

Disqualifiers: Non-secretory myeloma, POEMS syndrome, Waldenstrom's, 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: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of a combination of three drugs—carfilzomib, lenalidomide, and dexamethasone—before and after a stem cell transplant in treating newly diagnosed multiple myeloma, a type of blood cancer. Carfilzomib (Kyprolis) blocks enzymes that cancer cells need to grow, lenalidomide (Revlimid) boosts the immune system to fight cancer, and dexamethasone kills cancer cells. The trial aims to determine if this approach can kill more cancer cells and improve patient outcomes. People newly diagnosed with multiple myeloma who need chemotherapy might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

The trial information does not specify if you need to stop taking your current medications. However, certain medications like bisphosphonates are allowed, and there are restrictions on recent treatments like radiotherapy and investigational drugs. It's best to discuss your specific medications with the trial team.

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

Research has shown that the combination of carfilzomib, lenalidomide, and dexamethasone is generally well-tolerated by patients, even those with prior treatments. One study found that this combination, often called KRd, was effective and safe, yielding good results without severe side effects. Another study found that adding another drug to this mix did not cause major safety issues, suggesting the main treatment is safe.

While side effects can occur with any treatment, these studies suggest that most patients manage this combination well. This is encouraging news for those considering joining a trial with these drugs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Carfilzomib, Lenalidomide, and Dexamethasone with a stem cell transplant for multiple myeloma because it offers a unique multi-faceted approach. Unlike standard treatments like Bortezomib and Melphalan, this combination includes Carfilzomib, a next-generation proteasome inhibitor, which potentially offers a more effective blockade of protein breakdown in cancer cells. Lenalidomide adds an immune-modulating effect, enhancing the body's ability to fight cancer, while Dexamethasone reduces inflammation and helps manage symptoms. This combination aims to not only target the cancer cells more effectively but also maintain a longer-lasting remission, which is an exciting prospect for improving patient outcomes.

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

Research shows that a combination of three drugs—carfilzomib, lenalidomide, and dexamethasone—can effectively treat multiple myeloma, a type of blood cancer. In this trial, participants will receive this combination as part of their treatment regimen. Studies have found that this combination helps patients live longer, especially those whose cancer has returned or did not respond to previous treatments. Carfilzomib blocks certain proteins that cancer cells need to grow, lenalidomide helps the immune system fight the cancer, and dexamethasone kills cancer cells or stops them from multiplying. Past studies indicate that patients generally tolerated this treatment well, even after many other treatments. This suggests it could also be a good option for newly diagnosed patients. ^{1 5 6 7 8}

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 with newly diagnosed multiple myeloma who can follow the study plan, including birth control and testing. They must have certain blood cell counts, organ function, and agree to not get pregnant or father a child. People with recent major surgery, other cancers within 3 years (except some skin cancers), heart issues, uncontrolled diabetes or hypertension, active infections, HIV or hepatitis cannot join.

Inclusion Criteria

You are expected to live for more than 3 months.

Subjects must agree to adhere to all study requirements, including birth control measures and pregnancy testing, visit schedule, outpatient treatment, required concomitant medications, and laboratory monitoring

I have been newly diagnosed with myeloma and need chemotherapy.

Exclusion Criteria

You have had an allergic reaction to mannitol in the past.

I have Waldenstrom's macroglobulinemia or IgM myeloma.

I haven't had cancer in the last 3 years, except for certain skin, thyroid, cervix, or low-grade prostate cancers.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants receive dexamethasone, carfilzomib, and lenalidomide for 4 cycles

16 weeks

Multiple visits for drug administration

Transplant

Participants undergo autologous stem cell transplant

1-2 weeks

Inpatient stay for transplant procedure

Consolidation Therapy

Participants receive dexamethasone, carfilzomib, and lenalidomide for 4 cycles as in induction

16 weeks

Multiple visits for drug administration

Maintenance Therapy

Participants receive dexamethasone, carfilzomib, and lenalidomide for 10 cycles

40 weeks

Multiple visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Hematopoietic Stem Cell Transplantation
• Carfilzomib
• Dexamethasone
• Lenalidomide

Trial Overview The trial tests carfilzomib, lenalidomide & dexamethasone before/after stem cell transplant in treating new multiple myeloma patients. Carfilzomib blocks enzymes cancer cells need; lenalidomide stimulates the immune system; dexamethasone kills or stops cancer cells from dividing.

How Is the Trial Designed?

Group I: Treatment (dexamethasone, carfilzomib, lenalidomide) Experimental Treatment 5 Interventions

INDUCTION THERAPY: Patients receive dexamethasone IV or PO QD on days 1, 8, 15 and 22; carfilzomib IV over 10-30 minutes on days 1, 2, 8, 9, 15, and 16; and lenalidomide PO QD on days 1-21. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity.. TRANSPLANT: Patients undergo autologous stem cell transplant. CONSOLIDATION THERAPY: Patients receive dexamethasone, carfilzomib, and lenalidomide as in induction. Treatment repeats every 28 days for 4 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive dexamethasone and lenalidomide as in induction therapy and carfilzomib IV over 30 minutes on days 1, 2, 15, and 16. Treatment repeats every 28 days for 10 courses 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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. 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 ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40447540/

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

3. haematologica.org haematologica.org/article/view/haematol.2024.285534

Superior outcomes and high-risk features with carfilzomib ... Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma ...

4. nature.com nature.com/articles/s41408-025-01256-2

Carfilzomib prescribing patterns and outcomes for relapsed ... Our findings do not support improved outcomes with twice-weekly carfilzomib in RRMM. K56-1x may provide the best balance of efficacy, safety, and avoidance of ...

5. nejm.org nejm.org/doi/full/10.1056/NEJMoa1411321

Carfilzomib, Lenalidomide, and Dexamethasone for ... The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple ...

6. 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 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9240591/

Real-world effectiveness and safety analysis of carfilzomib ... Real-world effectiveness and safety analysis of carfilzomib–lenalidomide–dexamethasone and carfilzomib–dexamethasone in relapsed/refractory multiple myeloma

8. ashpublications.org ashpublications.org/bloodadvances/article/8/19/5012/517073/A-R-R-O-W-2-once-vs-twice-weekly-carfilzomib

A.R.R.O.W.2: once- vs twice-weekly carfilzomib, lenalidomide ... This open-label, phase 3, multicenter, randomized study aimed to demonstrate noninferiority of the overall response rate (ORR) for once-weekly carfilzomib.