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Proteasome Inhibitor

Quadruple Therapy for Multiple Myeloma (ADVANCE Trial)

Phase 2

Recruiting

Led By Carl Landgren, MD

Research Sponsored by University of Miami

Eligibility Criteria Checklist

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

Must have

Eastern Cooperative Oncology Group (ECOG) performance status 0-2

Females of childbearing potential (FCBP) must have a negative pregnancy test and use effective birth control methods

Must not have

Uncontrolled gastrointestinal disease, significant neuropathy, contraindication to concomitant medication, and recent major surgery

Patients with certain infections including HIV, hepatitis B or C, and active Coronavirus Disease of 2019 (COVID-19) infection

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing whether two different treatments for multiple myeloma are safer and more effective than the current standard of care.

Who is the study for?

Adults aged 18-75 with newly diagnosed Multiple Myeloma, able to perform daily activities (ECOG 0-2), and have good heart, kidney, liver, and blood function. Participants must not have had more than one cycle of prior MM treatment or exposure to certain drugs. They should be free from significant heart disease, uncontrolled diabetes or hypertension, severe lung conditions like COPD, and active infections including HIV and COVID-19.

What is being tested?

The trial is testing if a combination of carfilzomib, lenalidomide & dexamethasone (KRD) alone or with Daratumumab (KRD+DARA) is safer/more effective for controlling multiple myeloma compared to the standard care combo of lenalidomide, bortezomib & dexamethasone (VRD).

What are the potential side effects?

Possible side effects include allergic reactions due to Diphenhydramine; nerve damage from Bortezomib; infusion-related reactions from Daratumumab; high blood sugar levels from Dexamethasone; increased risk of infection due to Lenalidomide; lung issues related to Montelukast; liver toxicity from Acetaminophen; and 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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I am able to care for myself and perform daily activities.

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I am able to have children, not pregnant, and use birth control.

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My condition has caused damage to my organs or meets specific criteria for myeloma.

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I can undergo treatments to prevent blood clots.

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I am between 18 and 75 years old.

Exclusion Criteria

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

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I do not have severe stomach issues, nerve pain, drug allergies, or recent major surgery.

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I do not have HIV, hepatitis B or C, or active COVID-19.

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I have conditions like leukemia, COPD, high blood pressure, or diabetes that are not well-controlled.

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I have a serious heart condition or recently had a heart attack.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 3 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

Rate of Minimal Residual Disease (MRD) Negativity

Secondary study objectives

Event Free Survival (EFS)

Incidence of treatment related toxicity

Minimal Residual Disease (MRD) Negativity

+4 more

Side effects data

From 2021 Phase 3 trial • 126 Patients • NCT03029234

62%

Anaemia

49%

Upper respiratory tract infection

49%

Platelet count decreased

39%

White blood cell count decreased

38%

Hypertension

35%

Hypokalaemia

30%

Neutrophil count decreased

28%

Lymphocyte count decreased

23%

Pneumonia

21%

Cough

19%

Blood creatinine increased

19%

Insomnia

18%

Pyrexia

17%

Hyperuricaemia

17%

Diarrhoea

16%

Hypocalcaemia

16%

Neutrophil count increased

16%

Hypoalbuminaemia

16%

Blood lactate dehydrogenase increased

15%

Blood pressure increased

15%

Blood uric acid increased

15%

Lung infection

14%

Blood bilirubin increased

14%

Hyperglycaemia

14%

White blood cell count increased

14%

Blood glucose increased

14%

Constipation

12%

Neutrophil percentage increased

12%

Blood urea increased

11%

Alanine aminotransferase increased

11%

Hypercalcaemia

11%

Hyponatraemia

10%

Bronchitis

10%

Blood potassium decreased

10%

Oedema peripheral

10%

Neuropathy peripheral

10%

Productive cough

10%

Aspartate aminotransferase increased

10%

Lymphocyte percentage decreased

Leukocytosis

Hypoproteinaemia

Influenza

Blood albumin decreased

Blood phosphorus increased

Peripheral swelling

Back pain

Hypophosphataemia

Mean cell volume increased

Prealbumin decreased

Bilirubin conjugated increased

Vomiting

Abdominal distension

Cataract

Nasopharyngitis

Hypoglycaemia

Gamma-glutamyltransferase increased

Thrombocytopenia

Hyperkalaemia

Hepatic function abnormal

Respiratory tract infection

Nausea

Vision blurred

Plasma cell myeloma

Acute kidney injury

Bone pain

Localised infection

Cardiac amyloidosis

Hypotension

Chronic kidney disease

Interstitial lung disease

Pleural effusion

Deep vein thrombosis

Obstructive airways disorder

Myelopathy

Organising pneumonia

Myolipoma

Neuralgia

Asthma

Lipoma

Cerebral ischaemia

Nerve compression

Disease progression

Infusion site extravasation

Escherichia sepsis

Otitis media

Periodontitis

Pathological fracture

Pain

Device related infection

Dysuria

Soft tissue infection

Spinal compression fracture

Cardiac failure acute

Supraventricular tachycardia

Bronchiolitis

Pancreatitis acute

100%

80%

60%

40%

20%

Study treatment Arm

Carfilzomib With Dexamethasone

Awards & Highlights

No Placebo-Only Group

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

Trial Design

3Treatment groups

Experimental Treatment

Group I: Arm C- Carfilzomib, Lenalidomide and Dexamethasone with Daratumumab (DKrd)Experimental Treatment8 Interventions

Participants in this group will receive Carfilzomib, Lenalidomide, Dexamethasone with Daratumumab, Acetaminophen, Diphenhydramine and Montelukast on a 28 day cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years.

Group II: Arm B - Carfilzomib, Lenalidomide and Dexamethasone (KRD)Experimental Treatment4 Interventions

Participants in this group will receive Carfilzomib, Lenalidomide and Dexamethasone on a 28 day cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years.

Group III: Arm A - Bortezomib, Lenalidomide and Dexamethasone (VRD)Experimental Treatment4 Interventions

Participants in this group will receive Bortezomib, Lenalidomide and Dexamethasone on a 21 day treatment cycle. Participants achieving a PR or better at the end of 4 cycles will continue to receive a total of 8 cycles of combination therapy. Participants with less than PR after completing 4 cycles will go off study therapy. After 8 cycles of therapy, participants who are MRD positive will have the option to receive an ASCT if stem cells were able to be extracted, before initiating maintenance therapy with Lenalidomide for up to 2 years, and patients who are MRD negative will go directly on to receive maintenance therapy with Lenalidomide for up to 2 years.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Bortezomib

2005

Completed Phase 3

~1410

Daratumumab

2014

Completed Phase 3

~2000