Venetoclax + Carfilzomib + Dexamethasone for Multiple Myeloma

Not currently recruiting at 39 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AbbVie

Disqualifiers: Cardiovascular disease, Active infections, Diabetes, 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: Up to 17 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs—venetoclax (a targeted therapy), carfilzomib (a proteasome inhibitor), and dexamethasone (a corticosteroid)—to determine their safety and effectiveness for people with multiple myeloma, a type of blood cancer, who have not responded well to other treatments. It targets individuals who have tried 1 to 3 different treatments and have a specific genetic marker (t(11;14) positive) related to their myeloma. The study seeks participants whose multiple myeloma has returned or worsened after previous treatments. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research has shown that the combination of venetoclax, carfilzomib, and dexamethasone is generally safe for patients with multiple myeloma. Earlier studies found no new or unexpected safety issues with this combination. Patients experienced anticipated side effects that could be managed. While all medications can cause side effects, the available evidence considers the safety of this treatment acceptable. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Venetoclax, Carfilzomib, and Dexamethasone combination for multiple myeloma because it offers a novel approach compared to standard treatments like lenalidomide or bortezomib-based therapies. Venetoclax uniquely targets the BCL-2 protein, which plays a crucial role in cancer cell survival, offering a new mechanism of action that could potentially enhance treatment effectiveness. Additionally, this combination allows for dose adjustments and the possibility of continuing Venetoclax as a monotherapy, providing flexibility and potentially reducing side effects while maintaining efficacy. This innovative strategy could lead to more personalized and effective treatment options for patients with multiple myeloma.

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

Research has shown that adding venetoclax to carfilzomib and dexamethasone improves treatment response in multiple myeloma patients. In this trial, participants will receive the three-drug combination of venetoclax, carfilzomib, and dexamethasone. Studies have found that this combination is more effective than using carfilzomib and dexamethasone alone. Patients with a specific genetic marker, called t(11;14) positive, particularly benefit from this treatment. Early results suggest improved outcomes for those with relapsed or difficult-to-treat multiple myeloma. Overall, this combination shows promise in helping patients manage their condition more effectively. ^{1 5 6 7 8}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

This trial is for people with Multiple Myeloma who've had 1-3 prior treatments, can perform daily activities (ECOG score ≤2), and have a specific genetic marker (t(11;14) positive). They must have measurable disease, adequate blood counts, liver and kidney function. Excluded are those with certain MM types, other cancers within 3 years, severe infections including COVID-19 or hepatitis B/C, significant heart disease, recent major surgery or uncontrolled diabetes/hypertension.

Inclusion Criteria

You have a detectable amount of myeloma according to specific guidelines.

My recent blood tests meet the required levels for white blood cells, platelets, hemoglobin, and liver and kidney function.

My multiple myeloma has worsened or not responded to my last treatment.

Exclusion Criteria

I have a serious heart condition.

I have severe nerve pain or damage in my hands or feet.

Any other medical condition that, in the opinion of the Investigator, would adversely affect the participant's participation in the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Evaluate the safety and pharmacokinetic profiles to determine appropriate doses of venetoclax and carfilzomib

Approximately 6 months

Regular visits for dose adjustment and monitoring

Treatment

Participants receive the VenKd combination to evaluate safety and efficacy

Up to 17 months

Monthly visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Carfilzomib
• Dexamethasone
• Venetoclax

Trial Overview The study tests Venetoclax combined with Carfilzomib and Dexamethasone in participants whose Multiple Myeloma has returned after treatment or didn't respond to the last therapy. It's an open-label Phase 2 trial where everyone knows what treatment they're getting. The goal is to find out how safe this combination is and how well it works.

How Is the Trial Designed?

Group I: Venetoclax + Carfilzomib + Dexamethasone Experimental Treatment 3 Interventions

Part 1: Evaluate the safety and pharmacokinetic profiles while providing information to determine the appropriate doses of venetoclax and carfilzomib (VenKd) to be used in the VenKd combination in approximately 18 participants. The dose levels are Venetoclax 400 mg or 800 mg; Carfilzomib 20/27 mg/m2, 20/70 mg/m2, and/or 20/56 mg/m2; Dexamethasone 40 mg Part 2: Further evaluate the safety and efficacy profile of the VenKd combination selected after completion of Part 1 in approximately 22 additional participants. Participants may discontinue Kd but may continue receiving venetoclax once daily (QD) as monotherapy. Part 3: Further evaluation of the efficacy of the VenKd combination after completion of Part 1 and Part 2 in 7 additional participants. Part 4, An additional 65 participants t(11;14) positive will receive varying doses of the VenKd combination or carfilzomib and dexamethasone

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?

AbbVie

Lead Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

Genentech, Inc; Onyx Therapeutics, Inc.

Collaborator

Trials

1

Recruited

120+

Published Research Related to This Trial

In a study involving 929 patients with relapsed or refractory multiple myeloma, carfilzomib combined with dexamethasone significantly improved median progression-free survival (18.7 months) compared to bortezomib with dexamethasone (9.4 months), indicating greater efficacy of carfilzomib.

While both treatments had serious adverse events, carfilzomib was associated with a higher rate of serious adverse events (48%) compared to bortezomib (36%), suggesting that while carfilzomib may be more effective, it also carries a higher risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Dimopoulos, MA., Moreau, P., Palumbo, A., et al.[2022]

In a phase 2 study involving 49 adults with relapsed/refractory multiple myeloma, the combination of venetoclax, carfilzomib, and dexamethasone (VenKd) demonstrated an overall response rate of 80%, with even higher rates (92%) in patients with the t(11;14) genetic alteration.

The treatment was generally well tolerated, with a median progression-free survival of 22.8 months, although some patients experienced significant side effects, including diarrhea and fatigue.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 2 study of venetoclax plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma. Costa, LJ., Davies, FE., Monohan, GP., et al.[2022]

Venetoclax, when combined with carfilzomib and dexamethasone, showed rapid initial effectiveness in two patients with multiple myeloma harboring the t(11,14)(q13;q32) genetic alteration, but the responses were short-lived, indicating a need for ongoing monitoring and potential adjustments in treatment.

The emergence of the t(11;14)(q13;q32) alteration during the disease progression highlights the importance of regular cytogenetic testing in multiple myeloma, as it can influence treatment strategies and outcomes in this challenging disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax in combination with carfilzomib and dexamethasone in relapsed/refractory multiple myeloma harboring t(11,14)(q13;q32): two case reports and a review of the literature. Abuelgasim, KA., Alherz, N., Alhejazi, A., et al.[2021]

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 trial involving 291 patients with relapsed or refractory multiple myeloma, venetoclax combined with bortezomib and dexamethasone significantly improved progression-free survival compared to placebo, with a median of 22.4 months versus 11.5 months (hazard ratio 0.63).

Despite its efficacy, the venetoclax group experienced higher rates of serious treatment-emergent adverse events, particularly infections, leading to increased mortality, which underscores the need for careful patient selection for this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial. Kumar, SK., Harrison, SJ., Cavo, M., et al.[2021]

The MUK Five trial is a phase II study comparing the effectiveness of a new combination treatment (carfilzomib, cyclophosphamide, and dexamethasone) against the standard treatment (cyclophosphamide, bortezomib, and dexamethasone) in patients with multiple myeloma at first relapse, involving participants who have received no more than one prior treatment.

The trial aims to determine if the new combination (CCD) is at least as effective as the standard treatment (CVD) in achieving significant response rates, while also assessing the potential benefits of maintenance therapy with carfilzomib for improving progression-free survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The MUK five protocol: a phase II randomised, controlled, parallel group, multi-centre trial of carfilzomib, cyclophosphamide and dexamethasone (CCD) vs. cyclophosphamide, bortezomib (Velcade) and dexamethasone (CVD) for first relapse and primary refractory multiple myeloma. Brown, S., Hinsley, S., Ballesteros, M., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8679663/

Phase 2 study of venetoclax plus carfilzomib and ... Outcomes for patients with multiple myeloma (MM) have improved over the past decade. However, MM remains incurable and invariably relapses. In ...

2. onclive.com onclive.com/view/venetoclax-carfilzomib-dexamethasone-triplet-shows-early-efficacy-in-t-11-14-r-r-myeloma

Venetoclax/Carfilzomib/Dexamethasone Triplet Shows ... The addition of venetoclax (Venclexta) to carfilzomib (Kyprolis) and dexamethasone increased response rates compared with carfilzomib plus dexamethasone alone.

3. abbvieclinicaltrials.com abbvieclinicaltrials.com/study/?id=M15-538

Study of Venetoclax in Combination With Carfilzomib and ... A Phase 2, open-label, dose escalation study to evaluate the safety and efficacy of venetoclax in combination with carfilzomib-dexamethasone (Kd)

4. nature.com nature.com/articles/s41408-025-01264-2

Venetoclax-based treatment combinations in relapsed ... Outcomes for patients with multiple myeloma (MM) have improved significantly over the past decade with several new approved modalities [1].

5. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(25)00139-5/abstract

Venetoclax or placebo in combination with bortezomib and ... The phase 3 BELLINI primary endpoint was met, showing superior progression-free survival with venetoclax versus placebo plus bortezomib and dexamethasone.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01794520

NCT01794520 | Study Evaluating ABT-199 in Participants ... This study also assessed the safety profile and PK of venetoclax in combination with dexamethasone in participants with t(11;14)-positive multiple myeloma. The ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5030378/

New investigational drugs with single-agent activity in ... Venetoclax (ABT-199) is a potent, selective oral drug that specifically acts to inhibit Bcl-2, a well-known regulator of apoptosis. Myeloma cells are especially ...

8. jmedicalcasereports.biomedcentral.com jmedicalcasereports.biomedcentral.com/articles/10.1186/s13256-020-02376-y

Venetoclax in combination with carfilzomib and ... Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed/refractory multiple myeloma. Blood ...