What is the mechanism of action of this treatment?

Venetoclax, a BCL-2 inhibitor, promotes apoptosis by inhibiting the BCL-2 protein, which cancer cells use to avoid cell death. Carfilzomib, a proteasome inhibitor, disrupts protein degradation, causing toxic protein accumulation and cell death. Dexamethasone, a corticosteroid, reduces inflammation and can induce apoptosis in cancer cells. These treatments are important for Multiple Myeloma patients as they target different pathways, enhancing the effectiveness of therapy and overcoming resistance.

What side effects are associated with this type of intervention?

The combination of Venetoclax (BCL-2 inhibitor), Carfilzomib (proteasome inhibitor), and Dexamethasone (corticosteroid) for treating Multiple Myeloma can lead to several side effects. Venetoclax may cause prolonged cytopenias, febrile neutropenia, gastrointestinal issues, fatigue, and edema. Carfilzomib is associated with cardiovascular problems, renal toxicity, and hematologic toxicities. Dexamethasone can result in hyperglycemia, increased infection risk, osteoporosis, and mood changes. The combination of these drugs requires careful monitoring to manage and mitigate these potential side effects.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Multiple Myeloma that are similar to the combination being studied with Venetoclax, Carfilzomib, and Dexamethasone. Carfilzomib, a proteasome inhibitor, has been approved for use in combination with Dexamethasone for relapsed or refractory Multiple Myeloma, showing improved overall response rates and progression-free survival. Bortezomib, another proteasome inhibitor, has also been widely used in combination with Dexamethasone and other agents. While Venetoclax, a BCL-2 inhibitor, is still under investigation for Multiple Myeloma, it has shown promise in combination with proteasome inhibitors and corticosteroids in clinical trials.

What other types of research exist?

Promising alternatives to Venetoclax, Carfilzomib, and Dexamethasone for Multiple Myeloma patients include: 1) Daratumumab, Bortezomib, and Dexamethasone, which has shown efficacy in relapsed or refractory cases; 2) Elotuzumab, Lenalidomide, and Dexamethasone, which has demonstrated extended progression-free survival; 3) Carfilzomib and Dexamethasone alone, which has shown improved overall response rates and progression-free survival compared to Bortezomib and Dexamethasone. These combinations offer different mechanisms of action and may be suitable based on individual patient profiles and prior treatments.

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Proteasome Inhibitor

Venetoclax + Carfilzomib + Dexamethasone for Multiple Myeloma

Phase 2

Waitlist Available

Research Sponsored by AbbVie

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Meets absolute neutrophil count, platelet count, hemoglobin, liver and kidney function laboratory values within 2 weeks prior to first dose of study drug

Documented relapsed or progressive Multiple Myeloma (MM) on or after any regimen or is refractory to the most recent line of therapy

Must not have

Significant cardiovascular disease

Peripheral neuropathy ≥ Grade 3 or ≥ Grade 2 with pain within 2 weeks prior to first dose

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to approximately 17 months

Awards & highlights

Summary

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.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Possible side effects include low blood cell counts leading to increased infection risk or bleeding problems; nerve damage causing pain or numbness; liver issues; digestive symptoms like nausea/vomiting; fatigue; muscle weakness from steroids like dexamethasone; potential heart complications due to carfilzomib.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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

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I can take care of myself and am up and about more than half of my waking hours.

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My cancer has a specific genetic change known as t(11;14).

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I have received at least one treatment for multiple myeloma.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a serious heart condition.

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

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I have been diagnosed with Waldenström's macroglobulinemia.

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I have not had major surgery in the last 4 weeks.

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I have active plasma cell leukemia.

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I have not had any other cancers, including MDS, in the last 3 years.

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I currently have an active COVID-19 infection.

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I have POEMS syndrome.

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My multiple myeloma does not produce high levels of M-protein.

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I have been diagnosed with primary amyloidosis.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to approximately 17 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to approximately 17 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to approximately 17 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Multiple Myeloma

Number of Participants with Adverse Events

Multiple Myeloma

+1 more

Secondary study objectives

AUC from 0 to Infinity (AUC∞) of Carfilzomib

AUC from Time 0 to the Time of the Last Measurable Concentration (AUCt) of Carfilzomib

Area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) post-dose of Venetoclax

+13 more

Side effects data

From 2022 Phase 3 trial • 389 Patients • NCT02005471

33%

Neutropenia

11%

Sepsis

11%

SARS-CoV-2 test positive

11%

Abdominal pain

11%

Pneumonia

11%

Rhinovirus infection

11%

COVID-19

11%

Gastroenteritis

11%

Pneumonia pseudomonal

11%

Electrocardiogram QT prolonged

11%

Anaemia

11%

Neutrophil count decreased

11%

Hypokalaemia

11%

Febrile neutropenia

11%

Supraventricular tachycardia

11%

Blood creatinine increased

11%

White blood cell count decreased

11%

Dermatitis

100%

80%

60%

40%

20%

Study treatment Arm

Bendamustine + Rituximab Crossover Substudy

Venetoclax + Rituximab Re-Treatment Substudy

Venetoclax + Rituximab Main Study

Bendamustine + Rituximab Main Study

Trial Design

1Treatment groups

Experimental Treatment

Group I: Venetoclax + Carfilzomib + DexamethasoneExperimental Treatment3 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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Carfilzomib

2017

Completed Phase 3

~1310

Dexamethasone

2007

Completed Phase 4

~2640

Venetoclax

2019

Completed Phase 3

~2200

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Venetoclax, a BCL-2 inhibitor, promotes apoptosis by inhibiting the BCL-2 protein, which cancer cells use to avoid cell death. Carfilzomib, a proteasome inhibitor, disrupts protein degradation, causing toxic protein accumulation and cell death. Dexamethasone, a corticosteroid, reduces inflammation and can induce apoptosis in cancer cells. These treatments are important for Multiple Myeloma patients as they target different pathways, enhancing the effectiveness of therapy and overcoming resistance.

Chidamide and venetoclax synergistically exert cytotoxicity on multiple myeloma by upregulating BIM expression.Double remission of chronic lymphocytic leukemia and secondary acute myeloid leukemia after venetoclax monotherapy: A case report.A Novel MCL1 Inhibitor Combined with Venetoclax Rescues Venetoclax-Resistant Acute Myelogenous Leukemia.