What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, including CAR-T therapies like Ciltacabtagene Autoleucel, often have manageable but notable side effects. CAR-T therapy can cause fever, hypotension, and acute renal failure. Treatments involving Pomalidomide, Bortezomib, and Dexamethasone (PVd) or Daratumumab, Pomalidomide, and Dexamethasone (DPd) frequently result in hematologic adverse events such as thrombocytopenia and anemia, as well as non-hematologic effects like fatigue, nausea, diarrhea, hypertension, and infections. Carfilzomib, another common agent, can induce or worsen hypertension and peripheral neuropathy. These side effects are generally manageable with appropriate medical care.

What prior FDA approvals exist?

The FDA has approved several treatments for multiple myeloma, including CAR-T therapies and drugs targeting BCMA. Notably, idecabtagene vicleucel (Abecma) and ciltacabtagene autoleucel (Carvykti) are CAR-T therapies targeting BCMA, approved for relapsed or refractory multiple myeloma. Other approved treatments include proteasome inhibitors like bortezomib (Velcade) and carfilzomib (Kyprolis), immunomodulatory drugs such as lenalidomide (Revlimid) and pomalidomide (Pomalyst), and monoclonal antibodies like daratumumab (Darzalex). These therapies have shown efficacy in various stages of multiple myeloma treatment.

What other types of research exist?

Promising novel alternatives to Ciltacabtagene Autoleucel for Multiple Myeloma patients include: 1) Other CAR-T therapies such as CBM.CD19 CAR-T cells, which have shown efficacy in treating B-cell malignancies. 2) Combination regimens like Pomalidomide, Bortezomib, and Dexamethasone (PVd) or Daratumumab, Pomalidomide, and Dexamethasone (DPd), which are standard therapies being compared against Ciltacabtagene Autoleucel. 3) Immunotherapies targeting PD-1/PD-L1 pathways, which are being explored in various hematologic malignancies and may offer benefits in Multiple Myeloma.

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Other

CAR-T Therapy for Multiple Myeloma (CARTITUDE-4 Trial)

Phase 3

Waitlist Available

Research Sponsored by Janssen Research & Development, LLC

Eligibility Criteria Checklist

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

Must have

Be refractory to lenalidomide per IMWG consensus guidelines

Measurable disease at screening as defined by specific criteria related to serum monoclonal paraprotein (M-protein) level or urine M-protein level, or light chain multiple myeloma without measurable M-protein

Must not have

Received a cumulative dose of corticosteroids equivalent to >=70 mg of prednisone within the 7 days prior to randomization

Participants with Grade 1 peripheral neuropathy with pain or Grade 2 or higher peripheral neuropathy will not be permitted to receive specific therapies

Timeline

Screening 3 weeks

Treatment Varies

Follow Up until end of the study (up to 6 years)

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a new treatment called JNJ-68284528 (cilta-cel) for patients with multiple myeloma who haven't responded to other treatments. The treatment uses modified immune cells to better recognize and attack cancer cells. The goal is to see if this new treatment works better than standard therapies. Cilta-cel was approved earlier this year.

Who is the study for?

This trial is for people with multiple myeloma who've had 1-3 prior treatments including specific drugs, are lenalidomide-refractory, and meet certain lab value criteria. Not eligible if they've had CAR-T or BCMA-targeted therapies, recent high-dose steroids, antibody treatment within 21 days, chemotherapy within 14 days, or have unresolved severe side effects from past cancer therapy.

What is being tested?

The study compares JNJ-68284528 (a CAR-T cell therapy targeting BCMA) against standard therapies: PVd (Pomalidomide with Bortezomib and Dexamethasone) or DPd (Daratumumab with Pomalidomide and Dexamethasone), to see which is more effective for relapsed multiple myeloma patients.

What are the potential side effects?

CAR-T therapy can cause immune system reactions like fever and low blood pressure. Standard treatments may lead to nerve damage, fatigue, infection risk increase due to lowered white blood cell counts, bleeding issues from low platelets count, and possible heart complications.

Eligibility Criteria

Inclusion Criteria

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

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My condition did not improve after taking lenalidomide.

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My cancer can be measured by specific protein levels in my blood or urine.

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I've had 1-3 treatments before that included a PI and an IMiD.

Exclusion Criteria

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

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I have taken a lot of steroids, like prednisone, recently.

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I do not have severe nerve pain or damage.

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I have not received monoclonal antibody treatment in the last 21 days.

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I haven't had chemotherapy in the last 14 days.

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My side effects from past cancer treatments are mild or gone, except for hair loss.

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I haven't taken proteasome inhibitor drugs in the last 14 days.

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I have received treatments targeting BCMA.

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I have previously undergone CAR-T cell therapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ until end of the study (up to 6 years)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~until end of the study (up to 6 years)

This trial's timeline: 3 weeks for screening, Varies for treatment, and until end of the study (up to 6 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

Progression Free Survival (PFS)

Secondary study objectives

Change from Baseline in Health-Related Quality of Life (HRQoL) as Assessed by European Organisation for Research and Treatment of Cancer Quality-of-life Questionnaire Core 30 (EORTC-QLQ-C30) Scale Score

Change from Baseline in Health-Related Quality of Life as Assessed by European Quality of Life - 5 Dimensions-5 Levels (EQ-5D-5L) Scale Score

Change from Baseline in Health-Related Quality of Life as Assessed by MySIm-Q Scale Sore

+15 more

Side effects data

From 2022 Phase 1 & 2 trial • 126 Patients • NCT03548207

100%

Neutropenia

90%

Cytokine Release Syndrome

86%

Thrombocytopenia

76%

Anaemia

69%

Leukopenia

55%

Lymphopenia

34%

Diarrhoea

34%

Aspartate Aminotransferase Increased

31%

Upper Respiratory Tract Infection

31%

Alanine Aminotransferase Increased

28%

Cough

24%

Constipation

21%

Nausea

21%

Fatigue

21%

Hypoalbuminaemia

21%

Hypophosphataemia

17%

Vomiting

17%

Headache

14%

Arthralgia

14%

Pain in Extremity

14%

Dizziness

14%

Dyspnoea Exertional

14%

Nasal Congestion

10%

Decreased Appetite

10%

Asthenia

10%

Chills

10%

Oedema Peripheral

10%

Weight Decreased

10%

Hypokalaemia

10%

Dyspnoea

10%

Erythema

10%

Hypertension

Pneumonia

Peripheral Sensory Neuropathy

Anxiety

Abdominal Pain

Malaise

Pain

Pyrexia

Hyperbilirubinaemia

Rhinovirus Infection

Sinusitis

Blood Alkaline Phosphatase Increased

Gamma-Glutamyltransferase Increased

Serum Ferritin Increased

Weight Increased

Hypercalcaemia

Hypocalcaemia

Hyponatraemia

Muscle Spasms

Muscular Weakness

Musculoskeletal Pain

Immune Effector Cell-Associated Neurotoxicity Syndrome

Memory Impairment

Parosmia

Insomnia

Pollakiuria

Oropharyngeal Pain

Pruritus

Rash

Rash Maculo-Papular

Hypotension

Neuropathy Peripheral

Hypoxia

Tremor

Productive Cough

Rhinorrhoea

Febrile Neutropenia

Gait Disturbance

Atypical Pneumonia

Cytomegalovirus Viraemia

Gastroenteritis Cryptosporidial

Gastroenteritis Salmonella

Influenza

Sepsis

Cognitive Disorder

Facial Paralysis

Noninfective Encephalitis

Confusional State

Acute Kidney Injury

Pulmonary Haemorrhage

Sinus Tachycardia

Hypogammaglobulinaemia

International Normalised Ratio Increased

Hyperglycaemia

Hypomagnesaemia

Back Pain

Musculoskeletal Chest Pain

Myalgia

Dysgeusia

Pleural Effusion

100%

80%

60%

40%

20%

Study treatment Arm

Phase 1b (US Population)

Phase 2 (US Population)

Phase 2 (Japan Population)

Awards & Highlights

No Placebo-Only Group

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

Pivotal Trial

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

Trial Design

2Treatment groups

Experimental Treatment

Group I: Arm B: JNJ-68284528 (Ciltacabtagene Autoleucel [Cilta-cel])Experimental Treatment1 Intervention

Participants will receive at least one cycle of bridging therapy (PVd or DPd) and additional cycles of bridging therapy may be considered based on participant's clinical status and timing of availability of JNJ-68284528 (cilta-cel) along with conditioning regimen (cyclophosphamide 300 milligram \[mg\]/m\^2 intravenous \[IV\] and fludarabine 30 mg/m\^2 IV daily, for 3 days), and JNJ-68284528 (cilta-cel) infusion 0.75 \* 10\^6 chimeric antigen receptor (CAR)-positive viable T cells/ kilogram (kg).

Group II: Arm A: PVd or DPd (Standard Therapy)Experimental Treatment4 Interventions

Participants will receive either PVd or DPd as a standard therapy. In PVd treatment, participants will receive oral pomalidomide 4 mg on Days 1 to 14 in each cycle; bortezomib 1.3 mg/meter square (m\^2) SC on Days 1, 4, 8 and 11 (Cycles 1 to 8) and on Days 1 and 8 (Cycle 9 onwards) and oral dexamethasone 20 mg on Days 1, 2, 4, 5, 8, 9, 11 and 12 (Cycles 1 to 8) and Days 1, 2, 8 and 9 (Cycle 9 onwards). Each cycle will consist of 21 days. In DPd treatment, participants will receive daratumumab SC 1800 mg weekly on Days 1, 8, 15, and 22 (Cycles 1 and 2), every 2 weeks on Days 1 and 15 (Cycles 3 to 6) and every 4 weeks on Day 1 (Cycle 7 onwards); oral pomalidomide 4 mg on Days 1 to 21 (Cycle 1 onwards); dexamethasone 40 mg oral or IV weekly on Days 1, 8, 15, and 22 (Cycle 1 onwards). Each cycle will consist of 28 days. Participants will continue to receive PVd or DPd until confirmed PD, death, intolerable toxicity, withdrawal of consent, or end of the study, whichever occurs earlier.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

JNJ-68284528

2018

Completed Phase 2

~130

Bortezomib

2005

Completed Phase 3

~1410

Dexamethasone

2007

Completed Phase 4

~2650

Daratumumab

2014

Completed Phase 3

~2000

Pomalidomide

2011

Completed Phase 2

~1020

0 / 11Eligibility 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 CAR-T therapy targeting BCMA, proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. CAR-T therapy, such as Ciltacabtagene Autoleucel, involves modifying a patient's T-cells to target and destroy cancer cells expressing the B-cell maturation antigen (BCMA). Proteasome inhibitors, like bortezomib, disrupt the degradation of proteins within cancer cells, leading to cell death. Immunomodulatory drugs, such as lenalidomide, enhance the immune system's ability to fight cancer and inhibit tumor growth. Monoclonal antibodies, like daratumumab, target specific proteins on the surface of myeloma cells, marking them for destruction by the immune system. These treatments are crucial for Multiple Myeloma patients as they offer targeted and effective strategies to control the disease and improve survival rates.