What is the mechanism of action of this treatment?

Proteasome inhibitors, such as carfilzomib (Kyprolis) and bortezomib (Velcade), are key treatments for Multiple Myeloma. They work by blocking the proteasome, an enzyme complex responsible for degrading unneeded or damaged proteins. This blockage causes an accumulation of defective proteins, leading to cell stress and death, particularly in rapidly dividing myeloma cells. This mechanism is significant for patients as it directly targets cancer cells, potentially improving treatment efficacy and outcomes.

What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, such as Kyprolis (carfilzomib) and Velcade (bortezomib), often used with lenalidomide and dexamethasone, have several known side effects. Carfilzomib is associated with higher rates of serious infections, particularly in the lower respiratory tract, and can cause cardiovascular issues like hypertension and heart failure. Bortezomib frequently leads to peripheral neuropathy, which can be mitigated by subcutaneous administration and weekly dosing. Lenalidomide can increase the risk of thromboembolism and infections due to its immunomodulatory effects. Dexamethasone, a corticosteroid, can cause hyperglycemia, mood changes, and increased infection risk. Patients should discuss these potential side effects with their healthcare provider to manage and mitigate risks effectively.

What prior FDA approvals exist?

Kyprolis (carfilzomib) and Velcade (bortezomib) are both proteasome inhibitors that have been FDA-approved for the treatment of multiple myeloma. Velcade was the first proteasome inhibitor approved by the FDA in 2003 for patients with relapsed multiple myeloma. Kyprolis received FDA approval in 2012 for patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy. Both drugs are often used in combination with other agents such as lenalidomide and dexamethasone to enhance their efficacy. Other related proteasome inhibitors include ixazomib, which is approved for use in combination with lenalidomide and dexamethasone for patients who have received at least one prior therapy.

What other types of research exist?

Promising novel alternatives to Kyprolis (carfilzomib) and Velcade (bortezomib) for Multiple Myeloma patients include: <ol> <li>Daratumumab-based regimens, such as daratumumab, lenalidomide, and dexamethasone (DRd) or daratumumab, bortezomib, and dexamethasone (DVd).</li> <li></li> </ol> Isatuximab-based regimens, such as isatuximab, pomalidomide, and dexamethasone (IsaPd). 3. Elotuzumab-based regimens, such as elotuzumab, lenalidomide, and dexamethasone (ERd). 4. Venetoclax in combination with other agents for patients with specific genetic profiles. These regimens have shown improved efficacy and are considered effective for relapsed or refractory Multiple Myeloma.

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Proteasome Inhibitor

KRd vs VRd Regimens for Multiple Myeloma ((COBRA) Trial)

Phase 3

Waitlist Available

Led By Andrzej Jakubowiak, MD

Research Sponsored by University of Chicago

Eligibility Criteria Checklist

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

Must have

Patients must have received no prior radiotherapy to a large area of the pelvis (more than half of the pelvis)

Eastern Cooperative Oncology Group performance status of 0-1

Must not have

Uncontrolled or symptomatic angina, arrhythmia, hypertension, CHF, EF less than 40%, within 6 months prior to first dose

Prior or concurrent pulmonary embolism

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 5 years

Awards & highlights

Approved for 60 Other Conditions

Pivotal Trial

All Individual Drugs Already Approved

No Placebo-Only Group

Summary

This trial is testing two different combinations of medications for patients who have just been diagnosed with multiple myeloma. The medications work by killing cancer cells and boosting the immune system's ability to fight the cancer. A new type of therapy has shown promising results in treating multiple myeloma.

Who is the study for?

This trial is for adults with newly diagnosed multiple myeloma who haven't had chemotherapy or extensive radiotherapy. They must not have used bortezomib or lenalidomide before and should be fit enough for potential future stem cell transplant, though it's deferred during the trial. Participants need functioning major organs, no severe heart conditions, and can't be pregnant. Women of childbearing potential must use two forms of contraception.

What is being tested?

The study compares two drug combinations: Carfilzomib with Lenalidomide and Dexamethasone (KRd) versus Bortezomib with Lenalidomide and Dexamethasone (VRd). It aims to determine which regimen is more effective in treating patients who are new to treatment for multiple myeloma.

What are the potential side effects?

Potential side effects include fatigue, nausea, low blood counts leading to increased infection risk or bleeding problems, nerve damage causing numbness or pain, liver issues reflected by abnormal blood tests, allergic reactions during infusion of drugs, and possible heart complications.

Eligibility Criteria

Inclusion Criteria

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

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I haven't had radiation to more than half of my pelvis.

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I am fully active or can carry out light work.

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I have been diagnosed with symptomatic multiple myeloma.

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My bone marrow has more than 10% plasma cells or I have a confirmed plasmacytoma.

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I have newly diagnosed myeloma and need chemotherapy.

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My liver tests are within normal limits.

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I have never been treated with bortezomib or lenalidomide.

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My kidney function, measured by creatinine clearance, is normal or only slightly reduced.

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I have not received chemotherapy for my current illness.

Exclusion Criteria

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

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I haven't had serious heart issues like uncontrolled chest pain or heart failure in the last 6 months.

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I have had a blood clot in my lungs before or currently.

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I have been diagnosed with moderate or severe asthma or COPD.

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My multiple myeloma does not produce much protein.

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I haven't had a heart attack in the last 6 months and don't have severe heart issues.

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I have been diagnosed with amyloidosis.

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I haven't been in a drug study within the last 3 weeks or 5 drug half-lives.

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My diabetes is not under control.

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I cannot tolerate certain cancer medications like daratumumab or lenalidomide.

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I cannot or do not want to take blood clot prevention medication.

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I have mild to no diarrhea without taking medication for it.

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I have not taken antibiotics, antivirals, or antifungals for an infection in the last two weeks.

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I have POEMS syndrome.

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I have Waldenström's macroglobulinemia or IgM myeloma.

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My cancer has spread to my brain or spinal cord.

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I have been diagnosed with plasma cell leukemia.

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I have not had major surgery in the last 3 weeks.

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I have moderate to severe numbness, tingling, or pain in my hands or feet.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 5 years for reporting.

Treatment Details

Study Objectives

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

Secondary study objectives

The combination of drugs (KRd vs VRd) safety and tolerability based on patients response

Awards & Highlights

Approved for 60 Other Conditions

This treatment demonstrated efficacy for 60 other conditions.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

All Individual Drugs Already Approved

Therapies where all constituent drugs have already been approved are likely to have better-understood side effect profiles.

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Group I: VRD ArmExperimental Treatment3 Interventions

Patients assigned to this group will receive a combination of Bortezomib, lenalidomide and dexamethasone in 21-day cycles. Doses will vary

Group II: KRD ArmExperimental Treatment3 Interventions

Patients assigned to this group will receive a combination of carfilzomib, lenalidomide, and dexamethasone in 28 day cycles. Doses will vary

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Carfilzomib

FDA approved

Bortezomib D-mannitol

FDA approved

Dexamethasone

FDA approved

Lenalidomide

FDA approved

0 / 27Eligibility 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

Proteasome inhibitors, such as carfilzomib (Kyprolis) and bortezomib (Velcade), are key treatments for Multiple Myeloma. They work by blocking the proteasome, an enzyme complex responsible for degrading unneeded or damaged proteins. This blockage causes an accumulation of defective proteins, leading to cell stress and death, particularly in rapidly dividing myeloma cells. This mechanism is significant for patients as it directly targets cancer cells, potentially improving treatment efficacy and outcomes.

[Proteasome inhibitor].