What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, such as Isatuximab (an anti-CD38 monoclonal antibody) combined with lenalidomide and dexamethasone, often result in side effects like neutropenia, infections (including upper respiratory tract infections and pneumonia), and infusion-related reactions. Other notable adverse events include fatigue, diarrhea, hypertension, and anemia. Severe side effects can include grade 3 or higher neutropenia, pneumonia, and hypertension. Similar treatments, like Daratumumab, also share these side effects, emphasizing the need for careful monitoring and management during therapy.

What prior FDA approvals exist?

Isatuximab is an anti-CD38 monoclonal antibody approved for the treatment of relapsed or refractory multiple myeloma. Similar drugs include Daratumumab, another anti-CD38 monoclonal antibody, which has been approved for use in combination with other agents like lenalidomide and dexamethasone. Other related treatments include Elotuzumab, a monoclonal antibody targeting SLAMF7, which is also used in combination with lenalidomide and dexamethasone. These therapies have shown efficacy in improving progression-free survival and overall response rates in multiple myeloma patients.

What other types of research exist?

Promising novel alternatives to Isatuximab for Multiple Myeloma patients include: 1) Elotuzumab, another monoclonal antibody targeting SLAMF7, which has shown efficacy in combination with lenalidomide and dexamethasone. 2) Daratumumab, an anti-CD38 monoclonal antibody, which has been effective in various combinations, including with bortezomib and dexamethasone. 3) Selinexor, a selective inhibitor of nuclear export, which has shown promise in combination with bortezomib and dexamethasone. 4) Carfilzomib, a proteasome inhibitor, which has demonstrated efficacy in combination with dexamethasone. These alternatives have been evaluated in clinical trials and have shown potential for treating relapsed or refractory Multiple Myeloma.

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Corticosteroid

Isatuximab + Lenalidomide + Dexamethasone for Multiple Myeloma (ITHACA Trial)

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

The most common treatments for Multiple Myeloma include monoclonal antibodies like Isatuximab, proteasome inhibitors, and immunomodulatory drugs. Isatuximab targets CD38, a protein highly expressed on myeloma cells, leading to cell death through immune-mediated mechanisms. Proteasome inhibitors, such as bortezomib, disrupt protein degradation in cancer cells, causing apoptosis. Immunomodulatory drugs like lenalidomide enhance the immune system's ability to attack myeloma cells and inhibit their growth. These treatments are crucial as they target specific pathways involved in myeloma cell survival and proliferation, thereby improving patient outcomes and prolonging progression-free survival.

Phase 3

Waitlist Available

Research Sponsored by Sanofi

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 or 1 or 2

Capable of giving voluntary written informed consent

Must not have

Malabsorption syndrome or any condition that can significantly impact the absorption of lenalidomide

Women of childbearing potential or male participant with women of childbearing potential who do not agree to use a highly effective method of birth control

Timeline

Screening 3 weeks

Treatment Varies

Follow Up end of treatment (up to approximately 3 year)

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing a new drug combination (isatuximab, lenalidomide, and dexamethasone) in patients with high-risk smoldering multiple myeloma. The treatment aims to boost the immune system to fight cancer cells and prevent the disease from getting worse. Lenalidomide helps the immune system and directly targets cancer cells.

Who is the study for?

This trial is for people diagnosed within the last 5 years with high-risk smoldering multiple myeloma (SMM), which means they have certain levels of M-protein and bone marrow plasma cells but no severe symptoms. They should be able to perform daily activities with ease or with some limitations (ECOG Performance Status 0-2).

What is being tested?

The study tests if adding Isatuximab to Lenalidomide and Dexamethasone can prolong the time patients live without their disease getting worse, compared to just Lenalidomide and Dexamethasone. It's a Phase 3 trial where one group gets all three drugs, while another gets only two.

What are the potential side effects?

Possible side effects include reactions at the infusion site, increased risk of infections due to low blood cell counts, fatigue, digestive issues like constipation or diarrhea, and potential allergic reactions.

Eligibility Criteria

Inclusion Criteria

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

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I can take care of myself and am up and about more than half of my waking hours.

Select...

I can sign the consent form on my own.

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I was diagnosed with high-risk smoldering multiple myeloma within the last 5 years.

Exclusion Criteria

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

Select...

I do not have conditions that affect how my body absorbs medication.

Select...

I agree to use effective birth control during the study.

Select...

I do not have serious heart problems or recent heart attacks.

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My condition involves symptoms like high calcium, kidney issues, anemia, or bone problems due to myeloma.

Select...

I haven't had severe stomach issues, bowel diseases, or serious blood clots in the last 3 months.

Select...

I have been treated for cancer within the last 3 years.

Select...

I am currently taking more than 10 mg of prednisone or its equivalent daily.

Select...

I do not have AIDS, HIV needing treatment, or active hepatitis A.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ end of treatment (up to approximately 3 year)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~end of treatment (up to approximately 3 year)

This trial's timeline: 3 weeks for screening, Varies for treatment, and end of treatment (up to approximately 3 year) 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) Randomized Phase 3 Part

Receptor density/receptor occupancy Safety Run-in Part

Secondary study objectives

Complete response (CR) rate - Randomized Phase 3 Part

Duration of Response (DOR) - Safety Run-in Part

Duration of response (DOR) - Randomized Phase 3 Part

+22 more

Side effects data

From 2023 Phase 1 & 2 trial • 351 Patients • NCT01084252

54%

Infusion Related Reaction

42%

Cough

38%

Nausea

29%

Diarrhoea

29%

Upper Respiratory Tract Infection

29%

Back Pain

29%

Fatigue

25%

Insomnia

21%

Chills

21%

Dyspnoea

21%

Headache

21%

Oedema Peripheral

21%

Pyrexia

21%

Arthralgia

17%

Pneumonia

17%

Constipation

17%

Vomiting

17%

Chest Discomfort

17%

Dehydration

17%

Myalgia

17%

Oropharyngeal Pain

13%

Productive Cough

13%

Bone Pain

13%

Non-Cardiac Chest Pain

13%

Oral Candidiasis

13%

Decreased Appetite

13%

Hypercalcaemia

13%

Hypokalaemia

13%

Nasal Congestion

13%

Anaemia

Upper-Airway Cough Syndrome

Peripheral Sensory Neuropathy

Sinus Congestion

Abdominal Pain Upper

Dysphagia

Nasopharyngitis

Influenza

Asthenia

Influenza Like Illness

Fall

Blood Creatinine Increased

Dyspnoea Exertional

Muscle Spasms

Pain In Extremity

Restless Legs Syndrome

Hypertension

Hypotension

Malaise

Bronchitis

Spinal Stenosis

Flank Pain

Pneumonia Viral

Urinary Tract Infection

Pneumonia Aspiration

Lacrimation Increased

Infective Aortitis

Pneumonia Mycoplasmal

Sepsis

Aortic Aneurysm

Cerebral Haemorrhage

Anaphylactic Reaction

Herpes Zoster

Septic Shock

Pathological Fracture

Spinal Cord Compression

Bronchospasm

Musculoskeletal Chest Pain

Dry Eye

Dry Mouth

Gastrooesophageal Reflux Disease

Toothache

Hypoaesthesia

Varicella Zoster Virus Infection

Neutropenia

Pain

Peripheral Swelling

Procedural Pain

Hyperkalaemia

Neutrophil Count Decreased

Hypocalcaemia

Epistaxis

Muscular Weakness

Dizziness

Dysgeusia

Agitation

Anxiety

Depression

Acute Kidney Injury

Rhinorrhoea

Sneezing

Throat Irritation

Throat Tightness

Hyperhidrosis

Flushing

Pneumonia Respiratory Syncytial Viral

Spinal Column Stenosis

Pelvic Pain

100%

80%

60%

40%

20%

Study treatment Arm

Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W

Phase 1: Isatuximab 20mg/kg QW

Phase 1: Isatuximab <=1 mg/kg Q2W

Phase 1: Isatuximab 3mg/kg Q2W

Phase1:Isatuximab (CD38+HM and Standard Risk Multiple Myeloma)

Phase 1: Isatuximab 20mg/kg Q2W

Phase 2 Stage 2: Isatuximab Alone

Phase 2 Stage 1a: Isatuximab 10mg/kg Q2W; Then Q4W

Phase 1: Isatuximab 5mg/kg Q2W

Phase 2 Stage 1b: Isatuximab 20 mg/kg QW and Then Q2W

Phase 2 Stage 2: Isatuximab + Dexamethasone

Phase 2 Stage 1a: Isatuximab 3mg/kg Q2W

Phase 1: Isatuximab (CD38 + HM and High Risk Multiple Myeloma)

Phase 1: Isatuximab 10mg/kg QW

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

Active Control

Group I: Isatuximab, lenalidomide, and dexamethasone (ILd)Experimental Treatment7 Interventions

Participants will receive isatuximab \[intravenous (IV) administration\] in combination with lenalidomide \[per os (PO) administration\] and dexamethasone \[IV on Day 1 of Cycle 1 for participants receiving isatuximab IV only and PO otherwise for subsequent cycles\] for 24 cycles followed by isatuximab monotherapy for 12 cycles for a total duration of 36 cycles. 1 cycle = 28 days. Participants may receive other treatments as pre-medication.

Group II: Lenalidomide and dexamethasone (Ld)Active Control2 Interventions

Lenalidomide \[PO administration\] in combination with dexamethasone \[PO administration\] for 24 cycles. 1 cycle = 28 days

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Isatuximab SAR650984

2015

Completed Phase 2

~580

Acetaminophen

2017

Completed Phase 4

~2030

Methylprednisolone or equivalent

2007

Completed Phase 4

~50

Lenalidomide

2005

Completed Phase 3

~2240

Dexamethasone

2007

Completed Phase 4

~2650

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 monoclonal antibodies like Isatuximab, proteasome inhibitors, and immunomodulatory drugs. Isatuximab targets CD38, a protein highly expressed on myeloma cells, leading to cell death through immune-mediated mechanisms. Proteasome inhibitors, such as bortezomib, disrupt protein degradation in cancer cells, causing apoptosis. Immunomodulatory drugs like lenalidomide enhance the immune system's ability to attack myeloma cells and inhibit their growth. These treatments are crucial as they target specific pathways involved in myeloma cell survival and proliferation, thereby improving patient outcomes and prolonging progression-free survival.