What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, particularly those involving monoclonal antibodies like daratumumab, elotuzumab, and isatuximab, often lead to side effects such as neutropenia, lymphocytopenia, and increased infection rates, including pneumonia and viral reactivations (e.g., herpes zoster, CMV). Daratumumab, when combined with other drugs like lenalidomide, dexamethasone, and bortezomib, has been associated with higher rates of grade 3 or 4 infections, infusion-related reactions, and hematologic toxicities such as anemia and thrombocytopenia. Elotuzumab and isatuximab also show similar side effects, with additional risks of hypertension and gastrointestinal issues like diarrhea.

What prior FDA approvals exist?

Daratumumab, an anti-CD38 monoclonal antibody, has been approved by the FDA for the treatment of Multiple Myeloma in various settings, including newly diagnosed and relapsed/refractory cases. Other similar monoclonal antibodies include isatuximab, which also targets CD38 and has been approved for relapsed/refractory Multiple Myeloma. Additionally, elotuzumab, targeting SLAMF7, has been approved in combination with lenalidomide and dexamethasone. These approvals highlight the effectiveness of monoclonal antibodies in combination with other agents like lenalidomide, bortezomib, and dexamethasone in treating Multiple Myeloma.

What other types of research exist?

Promising novel alternatives to Daratumumab for Multiple Myeloma patients include: 1) Bispecific T cell engagers (BiTEs) such as teclistamab (targeting BCMA and CD3) and talquetamab (targeting GPRC5D and CD3), 2) Chimeric Antigen Receptor (CAR) T cell therapies like idecabtagene vicleucel and ciltacabtagene autoleucel, 3) Antibody-drug conjugates such as belantamab mafodotin (targeting BCMA), and 4) CELMoDs targeting cereblon, such as iberdomide and CC92480.

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Proteasome Inhibitor

Daratumumab Combination Therapy for Multiple Myeloma

Phase 2

Waitlist Available

Led By Neha Korde, MD

Research Sponsored by Memorial Sloan Kettering Cancer Center

Eligibility Criteria Checklist

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

Must have

Men must agree to use a latex condom during sexual contact with a FCBP

Evidence of underlying end organ damage and/or myeloma defining event attributed to underlying plasma cell proliferative disorder

Must not have

Specific medical conditions including plasma cell leukemia, POEMS syndrome, amyloidosis, chronic obstructive pulmonary disease, pregnancy, lactation, uncontrolled hypertension or diabetes, active hepatitis B or C infection, human immunodeficiency virus (HIV) seropositivity, significant cardiovascular disease, pulmonary hypertension, refractory GI disease, significant neuropathy, contraindication to any concomitant medication, and major surgery within 3 weeks prior to first dose

Patients receiving >1 cycle of prior treatment or concurrent systemic treatment for multiple myeloma

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new treatment combining four drugs to see if it is safe for patients with multiple myeloma. The drugs work together to attack cancer cells in different ways, making it harder for the cancer to survive. The introduction of new treatments has greatly improved survival outcomes.

Who is the study for?

This trial is for newly diagnosed multiple myeloma patients with measurable disease, specific organ damage, and certain blood and liver function levels. Participants must not have had more than one cycle of prior treatment. Women who can bear children and men must follow strict birth control rules.

What is being tested?

The study tests the safety and effectiveness of daratumumab combined with carfilzomib, lenalidomide, and dexamethasone in treating multiple myeloma. The goal is to determine if this drug mix is safe for patients.

What are the potential side effects?

Possible side effects include immune system reactions, infusion-related reactions from daratumumab; blood clots or bone thinning from dexamethasone; kidney problems or low blood counts from lenalidomide; heart issues or lung complications from carfilzomib.

Eligibility Criteria

Inclusion Criteria

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

Select...

I agree to use a latex condom during sex with a female capable of becoming pregnant.

Select...

My condition has caused damage to my organs or significant health events due to a plasma cell disorder.

Select...

I have been recently diagnosed with multiple myeloma.

Exclusion Criteria

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

Select...

I do not have specific conditions like uncontrolled diabetes, heart disease, or recent major surgery.

Select...

I have received more than one cycle of treatment for multiple myeloma.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and 2 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

assess the rate of MRD negativity

Side effects data

From 2020 Phase 1 & 2 trial • 22 Patients • NCT02841033

86%

Diarrhea

82%

Cough

82%

Lymphocyte count decreased

77%

Creatinine Increased

73%

Fatigue

73%

Hypertriglyceridemia

68%

Anemia

64%

Hypermagnesemia

64%

Myalgia

64%

Headache

59%

Cholesterol high

59%

Hyperuricemia

59%

Nausea

55%

Back pain

55%

Insomnia

50%

Hypoalbuminemia

50%

Dizziness

50%

Chronic kidney disease

50%

Upper respiratory infection

45%

Sore throat

45%

Edema limbs

45%

Alkaline phosphatase increased

45%

Cardiac troponin I increased

45%

CPK increased

45%

Platelet count decreased

45%

Pain in extremity

45%

Bruising

41%

Nasal congestion

41%

Dyspnea

36%

Abdominal pain

36%

Constipation

36%

Paresthesia

36%

Vomiting

36%

Rhinitis infective

36%

Aspartate aminotransferase increased (AST)

36%

Hypophosphatemia

36%

Metabolic and nutrition disorders - other, specify: iron deficiency

32%

Rhinorrhea

32%

Abdominal distention

32%

Eye disorders - other, specify: subconjunctival hemorrhage

32%

Fever

32%

Arthalgia

32%

Neck pain

32%

Anorexia

32%

Hyponatremia

32%

Rash maculopapular

27%

Post nasal drip

27%

Productive cough

27%

Total bilirubin increased

27%

White blood cell decreased

27%

Hyperkalemia

27%

Hoarseness

23%

Neutrophil count decreased

23%

Hypoglycemia

23%

Hematuria

23%

Urinary frequency

23%

Hypercalcemia

18%

Atrial fibrillation

18%

Chills

18%

Musculoskeletal and connective tissue disorder - other, specify: Restless legs

18%

Hyperglycemia

18%

Epistaxis

14%

Hyperthyroidism

14%

Blurred vision

14%

Acute kidney injury

14%

Heart failure

14%

Lung infection

14%

Ear pain

14%

Tinnitus

14%

Localized Edema

14%

Hypocalcemia

14%

Flank pain

14%

Peripheral sensory neuropathy

14%

Nocturia

14%

Allergic Rhinitis

14%

Endocrine disorder - other, specify: TSH elevated

14%

Gastroesophageal Reflux

14%

Oral pain

14%

Sinusitis

14%

Pruritus

14%

Rash acneiform

14%

Skin and Subcutaneous tissue disorders - other, specify: bug bite

14%

Skin and Subcutaneous tissue disorders - other, specify: Laceration

14%

Hypertension

Dysgeusia

Congestion

Conjunctivitis

Alopecia

Sepsis

Syncope

Palpitations

Hearing loss

Dry eye

Flu like symptoms

Fall

Investigations - other, specify: Lactate dehydrogenase elevated

Metabolic and nutrition disorders - other, specify: Type 2 diabetes mellitus

Neck stiffness

Proteinuria

Gastrointestinal disorder - other, specify: Tooth extraction

Gastrointestinal disorder - other, specify: inguinal hernia

Serum amylase increased

Weight gain

Dehydration

Metabolic and nutrition disorders - other, specify: increased appetite

Tremor

Anxiety

Depression

Dry Skin

Nail infection

Surgical procedure - other, specify: pre-cancerous areas removed

Periorbital edema

Cataract

Eye disorders - other, specify: obstructive tear duct

Eye disorders - other, specify: redness

Eye disorders - other, specify: scleral abrasian

Vaginal infection

Alanine aminotransferase increased (ALTT)

Wheezing

Hypothyroidism

Watering eyes

Bloating

Gastrointestinal hemorrhage - melena

Myocardial infarction (NSTEMI)

Renal and urinary disorders - other, UTI sepsis

Thromboembolic event

Upper gastrointestinal bleeding

Urinary tract infection

Urine output decreased

Lymph node pain

Chest pain - cardiac

Vertigo

Eye disorders - other, specify: cloudiness

Eye disorders - other, specify: Scotoma

Eye infection

Floaters

Anal hemorrhage

Dental caries

Dry mouth

Flatulence

Gait disturbance

Cystitis non-infective

Metabolic and nutrition disorders - other, specify: vitamin B12 deficiency

Arthritis

Generalized muscle weakness

Muscle weakness lower limb

Musculoskeletal and connective tissue disorder - other, specify: Dupuytren's contracture

Neoplasms - other, specify: basal cell carcinoma on sternum

Concentration impairment

Dysphagia

Memory impairment

Nervous system disorders - Other, specify: Autonomic Postural Hypotension

Irritability

Urinary incontinence

Urinary tract pain

Urinary urgency

Genital edema

Bronchospasm

Sleep apnea

Hypotension

CK increased

Colitis

Gastrointestinal disorder - other, specify: ulcer - Left lateral tongue

Gastrointestinal disorder - other, specify: viral gastroenteritis

Chest pain

Chest pain - non cardiac

Gastrointestinal disorder - other, specify: black stool

Gastrointestinal disorder - other, specify: broken tooth

Gastrointestinal disorder - other, specify: H. pylori

Immune system disorders - other, specify: lymphadenopathy

Laryngitis

Pharyngitis

Tooth infection

Weight loss

Hypokalemia

Hypomagnesemia

Agitation

Confusion (forgetfullness)

Mania

Hiccups

Hypoxia

Laryngeal inflammation

Photosensitivity

Rash

Skin & subcutaneous tissue disorders - other, specify: cercarial dermatitis/swimmer's itch

Skin and Subcutaneous tissue disorders - other, specify: Abrasion

Skin and Subcutaneous tissue disorders - other, specify: erythema

Skin and subcutaneous tissue disorders - other, specify: Skin sensitivity

Skin and Subcutaneous tissue disorders - other, specify: Wound

Skin induration

Surgical procedure - other, specify: Biopsy /wart removal

Surgical procedure - other, specify: biopsy, face, head, back

Surgical procedure - other, specify: shaved excision of dysplastic nevus

Arterial injury

Hot flashes

100%

80%

60%

40%

20%

Study treatment Arm

Daratumumab

Awards & Highlights

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: Cohort 2Experimental Treatment4 Interventions

Single arm, two-stage phase II trial of combination therapy (daratumumab, carfilzomib, lenalidomide, and dexamethasone for newly diagnosed multiple myeloma patients. Patients achieving ≥PR at end of 4 cycles will continue to receive the planned total of 8 cycles of combination therapy. Patients may go onto receiving additional maintenance phase therapy with lenalidomide under a separate treatment protocol. Patients ≤ PR after completing 4 cycles will go off study therapy.

Group II: Cohort 1Experimental Treatment4 Interventions

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

daratumumab

2017

Completed Phase 2

~180

dexamethasone

1995

Completed Phase 3

~9520

lenalidomide

2012

Completed Phase 3

~3370

carfilzomib

2010

Completed Phase 2

~710

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

Multiple Myeloma treatments often target specific cellular mechanisms to combat the disease. Daratumumab, a monoclonal antibody, targets CD38 on myeloma cells, leading to cell death through immune-mediated mechanisms. Proteasome inhibitors like bortezomib disrupt protein degradation, causing toxic protein accumulation in cancer cells. Immunomodulatory drugs such as lenalidomide enhance the immune system's ability to attack myeloma cells and inhibit their growth. These treatments are crucial as they target the unique biology of Multiple Myeloma, improving patient outcomes by reducing tumor burden and prolonging survival.

CD38 expression and complement inhibitors affect response and resistance to daratumumab therapy in myeloma.