What side effects are associated with this type of intervention?

Common treatments for Multiple Myeloma, such as daratumumab, often lead to side effects including neutropenia, lymphocytopenia, and increased risk of infections like pneumonia and viral reactivations (e.g., herpes zoster, CMV). Radioimmunotherapy, which combines monoclonal antibodies with radioactive isotopes, can add radiation-related side effects such as fatigue, nausea, and potential bone marrow suppression. These treatments require careful monitoring to manage and mitigate adverse effects.

What prior FDA approvals exist?

Daratumumab, an anti-CD38 monoclonal antibody, has been approved by the FDA for the treatment of relapsed or refractory Multiple Myeloma. It is often used in combination with other agents such as bortezomib, lenalidomide, and dexamethasone. Other similar treatments include elotuzumab, another monoclonal antibody targeting SLAMF7, used in combination with lenalidomide and dexamethasone. While radioimmunotherapy with Actinium-225 linked to daratumumab (225Ac-DOTA-daratumumab) is still under investigation, it represents a novel approach combining targeted monoclonal antibody therapy with radiotherapy.

What other types of research exist?

Promising novel alternatives to 225Ac-DOTA-daratumumab for Multiple Myeloma patients include: 1) Lutetium Lu 177 vipivotide tetraxetan, which has shown clinical efficacy in metastatic castration-resistant prostate cancer and is being studied for other cancers. 2) Trebananib (AMG 386), an angiopoietin-1/2 antagonist, which has shown antitumor activity in advanced solid tumors. 3) Lifastuzumab vedotin (DNIB0600A), an antibody-drug conjugate, which has shown safety and tolerability in recurrent platinum-sensitive ovarian cancer and may have potential in other cancers.

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Radioimmunotherapy

Radioimmunotherapy for Multiple Myeloma

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

Multiple Myeloma treatments often involve monoclonal antibodies, proteasome inhibitors, and immunomodulatory drugs. Monoclonal antibodies, such as daratumumab, target specific proteins on myeloma cells to induce cell death through immune-mediated mechanisms. Proteasome inhibitors, like bortezomib, disrupt protein degradation in cancer cells, leading to apoptosis. Immunomodulatory drugs, such as lenalidomide, enhance the immune system's ability to attack myeloma cells and inhibit their growth. Radioimmunotherapy, like 225Ac-DOTA-daratumumab, combines targeted antibody therapy with radioactive isotopes to deliver lethal radiation directly to cancer cells, minimizing damage to surrounding tissues. These mechanisms are crucial for effectively reducing tumor burden and improving patient outcomes in Multiple Myeloma.

Phase 1

Recruiting

Led By Scott R Goldsmith

Research Sponsored by City of Hope Medical Center

Eligibility Criteria Checklist

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

Must have

Men who are sexually active with a woman of childbearing potential must agree to use a barrier method of birth control

CD38 expression on multiple myeloma (MM) cells from bone marrow aspirate or biopsy as demonstrated by flow cytometry or immunohistochemistry

Must not have

Severe persistent asthma (forced expiratory volume in 1 second [FEV1] < 60% and/or daily symptoms) or severe chronic obstructive pulmonary disease (COPD)

Subject has uncontrolled human immunodeficiency virus (HIV-1), chronic or active hepatitis B, or active hepatitis A or C

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 12 months

Awards & highlights

Approved for 5 Other Conditions

No Placebo-Only Group

Summary

This trial tests a new treatment for patients with difficult-to-treat or returning multiple myeloma. The treatment aims to target and kill cancer cells more effectively by delivering radiation directly to them.

Who is the study for?

This trial is for adults over 18 with multiple myeloma that's resistant to treatment or has returned. They must have tried at least two prior therapies, including a proteasome inhibitor, an immunomodulatory drug, and anti-CD38 monoclonal antibody. Participants need good organ function and performance status, not be pregnant or breastfeeding, use effective birth control if applicable, and can't have other active cancers or severe lung/heart conditions.

What is being tested?

The trial tests the safety and optimal dose of a new therapy combining three agents: Actinium Ac 225-DOTA-daratumumab (radioimmunotherapy), Daratumumab (monoclonal antibody), and Indium In 111-DOTA-daratumumab (another radioimmunotherapy). This combination aims to target cancer cells more effectively in those with refractory or recurrent multiple myeloma.

What are the potential side effects?

Potential side effects include reactions related to the infusion of antibodies such as fever or chills; radiation-related issues like nausea; blood count changes leading to increased infection risk; liver function alterations; allergic responses; fatigue; heart complications due to radiation exposure.

Eligibility Criteria

Inclusion Criteria

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

Select...

I am a man and will use protection if I have sex with a woman who can have children.

Select...

My multiple myeloma cells show CD38 expression.

Select...

I am capable of becoming pregnant or fathering a child.

Select...

I have recovered from side effects of cancer treatment, except for hair loss.

Select...

I am 18 years old or older.

Select...

I can care for myself but may need occasional help.

Select...

I am a woman who can have children and my pregnancy test is negative.

Select...

I have undergone at least two different treatments.

Select...

I have multiple myeloma with measurable signs according to IMWG criteria.

Select...

I have been treated with drugs targeting proteins, immune system, and CD38.

Select...

My condition did not improve after taking daratumumab.

Exclusion Criteria

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

Select...

I have severe asthma or COPD with daily symptoms or low lung function.

Select...

I have uncontrolled HIV or active hepatitis.

Select...

I do not have unstable or poorly controlled chest pain.

Select...

I have another active cancer besides the one being treated.

Select...

I have severe heart failure.

Select...

I have not received any live vaccines in the last 4 weeks.

Select...

I have been diagnosed with a rare blood disorder.

Select...

I have had radiation on more than a quarter of my bone marrow.

Select...

I am currently undergoing chemotherapy, radiation, or biologic treatment for cancer.

Select...

I am not pregnant or breastfeeding.

Select...

I have not had major surgery in the last 14 days.

Select...

I have had radiopharmaceutical therapy before.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 12 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 12 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 12 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Incidence of dose-limiting toxicities (DLTs)

Maximum tolerated dose (MTD)

Secondary study objectives

12-month overall survival

Complete response rate

Duration of response

+3 more

Side effects data

From 2024 Phase 3 trial • 498 Patients • NCT02136134

44%

Thrombocytopenia

38%

Peripheral sensory neuropathy

38%

Peripheral Sensory Neuropathy

32%

Anaemia

24%

Fatigue

22%

Diarrhoea

17%

Upper respiratory tract infection

17%

Upper Respiratory Tract Infection

16%

Constipation

15%

Insomnia

15%

Asthenia

13%

Cough

11%

Nausea

11%

Neuralgia

11%

Pyrexia

11%

Dizziness

10%

Back Pain

10%

Pneumonia

10%

Back pain

10%

Neutropenia

Dyspnoea

Oedema peripheral

Oedema Peripheral

Pain in extremity

Hyperglycaemia

Pain in Extremity

Headache

Arthralgia

Paraesthesia

Bronchitis

Bone pain

Epistaxis

Bone Pain

Decreased Appetite

Hypocalcaemia

Dyspepsia

Leukopenia

Hypokalaemia

Decreased appetite

Lymphopenia

Oedema

Vomiting

Hypotension

Alanine aminotransferase increased

Abdominal pain

Nasopharyngitis

Alanine Aminotransferase Increased

Hypertension

Rash

Abdominal Pain Upper

Conjunctivitis

Hypophosphataemia

Abdominal pain upper

Influenza

Muscle Spasms

Musculoskeletal Chest Pain

Aspartate aminotransferase increased

Muscle spasms

Urinary tract infection

Myalgia

Herpes zoster

Musculoskeletal chest pain

Herpes Zoster

Pulmonary Embolism

Weight Decreased

Pulmonary embolism

Myocardial infarction

Dehydration

Myocardial Infarction

Lower Respiratory Tract Infection

Abdominal Pain

Orthostatic Hypotension

General Physical Health Deterioration

Condition aggravated

General physical health deterioration

Hyponatraemia

Orthostatic hypotension

Lower respiratory tract infection

Syncope

Productive cough

Nasal congestion

Respiratory failure

Weight decreased

Chills

Gastroenteritis

Sepsis

Respiratory Failure

Condition Aggravated

100%

80%

60%

40%

20%

Study treatment Arm

Bortezomib + Dexamethasone (Vd)

Daratumumab + Bortezomib and Dexamethasone (DVd)

Switch From Bortezomib + Dexamethasone (Vd) to Daratumumab Monotherapy

Awards & Highlights

Approved for 5 Other Conditions

This treatment demonstrated efficacy for 5 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: Treatment (daratumumab, 225Ac/111In-DOTA-daratumumab)Experimental Treatment3 Interventions

Patients receive daratumumab IV over 45 minutes. Two hours later, patients receive 111In-DOTA-daratumumab and 225Ac-DOTA-daratumumab IV over 20-30 minutes.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Daratumumab

FDA approved

0 / 23Eligibility 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 involve monoclonal antibodies, proteasome inhibitors, and immunomodulatory drugs. Monoclonal antibodies, such as daratumumab, target specific proteins on myeloma cells to induce cell death through immune-mediated mechanisms. Proteasome inhibitors, like bortezomib, disrupt protein degradation in cancer cells, leading to apoptosis. Immunomodulatory drugs, such as lenalidomide, enhance the immune system's ability to attack myeloma cells and inhibit their growth. Radioimmunotherapy, like 225Ac-DOTA-daratumumab, combines targeted antibody therapy with radioactive isotopes to deliver lethal radiation directly to cancer cells, minimizing damage to surrounding tissues. These mechanisms are crucial for effectively reducing tumor burden and improving patient outcomes in Multiple Myeloma.

Relapsed/Refractory multiple myeloma: defining refractory disease and identifying strategies to overcome resistance.Complement and cellular cytotoxicity in antibody therapy of cancer.