What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, such as lenalidomide, bortezomib, and dexamethasone, are associated with several side effects. Lenalidomide can cause fatigue, diarrhea, and an increased risk of blood clots. Bortezomib may lead to peripheral neuropathy, gastrointestinal issues, and thrombocytopenia. Dexamethasone often results in insomnia, hyperglycemia, and mood changes. Newer agents like carfilzomib can cause cardiovascular issues, including hypertension and heart failure, while ixazomib is generally well-tolerated but can cause gastrointestinal symptoms and rash. These side effects should be closely monitored and managed by healthcare providers.

What prior FDA approvals exist?

The FDA has approved several drugs for the treatment of Multiple Myeloma, including bortezomib, lenalidomide, and dexamethasone, which are often used in combination regimens. Bortezomib, a proteasome inhibitor, and lenalidomide, an immunomodulatory drug, have shown significant efficacy in both newly diagnosed and relapsed/refractory Multiple Myeloma. Additionally, daratumumab, a monoclonal antibody targeting CD38, has been approved for use in combination with these agents. These treatments are relevant in the context of minimal residual disease (MRD) assessment, as they aim to reduce cancer cell levels to undetectable amounts, which can be monitored using next-generation sequencing techniques.

What other types of research exist?

Promising novel alternatives to MRD assessment by NGS for Multiple Myeloma patients include advanced imaging techniques like PET-CT scans with novel tracers, digital droplet PCR (ddPCR) for highly sensitive detection of specific genetic mutations, and single-cell sequencing technologies. These methods offer high sensitivity and specificity for detecting low-level cancer cells and can provide valuable information to inform treatment decisions.

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Monoclonal Antibodies

DaraVRD for Multiple Myeloma

Q: What is the mechanism of action of this treatment?

The most common treatments for Multiple Myeloma include proteasome inhibitors (e.g., bortezomib), immunomodulatory drugs (e.g., lenalidomide), and monoclonal antibodies (e.g., daratumumab). Proteasome inhibitors work by blocking the proteasome's function, leading to the accumulation of proteins that induce cancer cell death. Immunomodulatory drugs enhance the immune system's ability to fight cancer cells and inhibit their growth. Monoclonal antibodies target specific proteins on the surface of myeloma cells, marking them for destruction by the immune system. These treatments are significant for Multiple Myeloma patients as they can reduce the disease burden to very low levels, which is essential for achieving MRD-negative status. MRD assessment by next-generation sequencing helps in detecting low-level cancer cells, allowing for more precise and effective treatment adjustments, ultimately improving patient outcomes.

Phase 2

Recruiting

Led By Susan Bal, MD

Research Sponsored by University of Alabama at Birmingham

Eligibility Criteria Checklist

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

Must have

Age >18 years with no upper age limit with a diagnosis of newly diagnosed multiple myeloma with indication for initiation of therapy with Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Be older than 18 years old

Must not have

Cerebrovascular disease manifested as prior stroke at any time or transient ischemic attack in the 12 months prior to initiation of therapy.

Major surgery, radiotherapy or infection requiring therapy within 14 days of starting treatment.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline through 7 years

Awards & highlights

All Individual Drugs Already Approved

Approved for 60 Other Conditions

No Placebo-Only Group

Summary

This trial uses a high-tech test to check for tiny amounts of leftover cancer cells in patients with newly diagnosed multiple myeloma. If no cancer cells are found, doctors might delay a major treatment called stem cell transplant. This approach aims to avoid the severe side effects of the transplant if it's not needed.

Who is the study for?

This trial is for adults with newly diagnosed multiple myeloma who haven't had much prior treatment. They must be expected to live at least a year, have good organ function, and agree to use contraception. It's important they can follow the study rules and are fit enough for stem cell transplant. At least 30% of participants will be ethnic/racial minorities.

What is being tested?

The MILESTONE trial is testing if using next-generation sequencing to check for minimal residual disease can help decide whether patients with new multiple myeloma can wait before having a stem cell transplant. The intervention being tested is DaraVRD.

What are the potential side effects?

Possible side effects include reactions related to immune system activation, such as infusion-related symptoms, liver issues reflected by increased enzymes or bilirubin levels, kidney problems shown by reduced clearance rates, blood disorders like anemia or clotting issues, and potential harm to unborn babies.

Eligibility Criteria

Inclusion Criteria

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

Select...

I am over 18, diagnosed with multiple myeloma, and need to start treatment.

Exclusion Criteria

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

Select...

I have had a stroke before or a temporary blockage of blood flow to my brain in the last year.

Select...

I haven't had major surgery, radiotherapy, or needed treatment for an infection in the last 14 days.

Select...

I have been diagnosed with POEMS syndrome or Waldenstrom's macroglobulinemia.

Select...

I haven't had a recent heart attack and my heart condition is stable.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline through 7 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline through 7 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline through 7 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Number of patients who are able to attain MRD<10-5 by next generation sequencing after 6 cycles of Dara-VRD and defer AHCT.

Secondary study objectives

Number of patients who was MRD>10-5 that undergo AHCT and attain MRD<10-5.

Overall survival

Progression free survival

Awards & Highlights

All Individual Drugs Already Approved

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

Approved for 60 Other Conditions

This treatment demonstrated efficacy for 60 other conditions.

No Placebo-Only Group

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

Trial Design

1Treatment groups

Experimental Treatment

Group I: Induction - Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (DaraVRD)Experimental Treatment1 Intervention

Quadruplet therapy with DaraVRD in the treatment of newly diagnosed myeloma

0 / 5Eligibility 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

The most common treatments for Multiple Myeloma include proteasome inhibitors (e.g., bortezomib), immunomodulatory drugs (e.g., lenalidomide), and monoclonal antibodies (e.g., daratumumab). Proteasome inhibitors work by blocking the proteasome's function, leading to the accumulation of proteins that induce cancer cell death. Immunomodulatory drugs enhance the immune system's ability to fight cancer cells and inhibit their growth. Monoclonal antibodies target specific proteins on the surface of myeloma cells, marking them for destruction by the immune system. These treatments are significant for Multiple Myeloma patients as they can reduce the disease burden to very low levels, which is essential for achieving MRD-negative status. MRD assessment by next-generation sequencing helps in detecting low-level cancer cells, allowing for more precise and effective treatment adjustments, ultimately improving patient outcomes.

How best to use new therapies in multiple myeloma.