Venetoclax + Carfilzomib + Dexamethasone for Multiple Myeloma

Recruiting at 35 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

120 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing a combination of three drugs to treat patients with multiple myeloma whose cancer has come back or didn't respond to previous treatments. The drugs work together to kill cancer cells and help manage side effects. The study aims to find out if this combination is safe and effective. Filanesib, one of the drugs in the trial, has shown durable activity in patients with multiple myeloma in previous studies.

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.

What data supports the effectiveness of the drug combination Venetoclax, Carfilzomib, and Dexamethasone for treating multiple myeloma?

A phase 2 study showed that the combination of Venetoclax, Carfilzomib, and Dexamethasone had an overall response rate of 80% in patients with relapsed or refractory multiple myeloma, with a median progression-free survival of 22.8 months. The response was particularly strong in patients with a specific genetic marker (t(11;14)). ^{1 2 3 4 5}

What makes the drug combination of Venetoclax, Carfilzomib, and Dexamethasone unique for treating multiple myeloma?

This drug combination is unique because Venetoclax targets a specific protein (BCL-2) that helps cancer cells survive, and when combined with Carfilzomib and Dexamethasone, it shows promising results, especially in patients with a specific genetic marker (t(11;14)). ^{1 2 3 5 6}

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

References

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

Phase 2 study of venetoclax plus carfilzomib and dexamethasone in patients with relapsed/refractory multiple myeloma. [2022]

2. England 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. [2021]

3. England 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. [2022]

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

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

5. England 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. [2021]

6. England 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. [2022]