Daratumumab Combo for Multiple Myeloma

Overseen By Kathleen P Research Nurse Coordinator, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Weill Medical College of Cornell University

Must be taking: Daratumumab

Must not be taking: Strong CYP3A inducers

Disqualifiers: Heart failure, HIV, Hepatitis, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of medications for multiple myeloma, a type of blood cancer. The goal is to determine if adding daratumumab (an immunotherapy drug) to a mix of clarithromycin, pomalidomide, and dexamethasone improves response rates in patients whose cancer has returned or not responded well to previous treatments. The trial targets those with relapsed or refractory multiple myeloma who have already received daratumumab, with specific conditions regarding their previous treatment responses. Participants must have measurable disease and be able to take aspirin daily. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot use certain medications like strong CYP3A inducers (e.g., rifampin, carbamazepine) or supplements like Ginkgo biloba or St. John's wort within 14 days before starting the trial. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the combination of daratumumab with clarithromycin, pomalidomide, and dexamethasone is generally well-tolerated by patients with multiple myeloma. Daratumumab, a key drug in this mix, has undergone extensive study. Common side effects include tiredness, pneumonia, and upper respiratory infections, which are usually mild to moderate and manageable.

Pomalidomide and dexamethasone have been used in treating multiple myeloma for a while. They can cause side effects like low blood cell counts and a higher risk of infections, but these are typically monitored and controlled during treatment.

Clarithromycin is an antibiotic that most people tolerate well, though it can sometimes cause stomach upset or mild allergic reactions.

Overall, while some side effects exist, the treatment is considered safe for patients with multiple myeloma. This is important because the treatment aims to improve response rates in patients previously treated with daratumumab. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for multiple myeloma?

Researchers are excited about the daratumumab combination treatment for multiple myeloma because it introduces a novel approach by combining multiple drugs that each play a specific role in attacking the cancer. Daratumumab is an antibody that targets a protein on myeloma cells, helping the immune system to identify and destroy these cells. By being administrated subcutaneously, daratumumab offers a more convenient and potentially less invasive delivery method compared to traditional intravenous infusions. Additionally, the combination with clarithromycin, pomalidomide, and dexamethasone enhances the overall therapeutic effect by utilizing their unique mechanisms, such as modulating the immune response and reducing inflammation, which might lead to better outcomes than existing treatments.

What evidence suggests that this trial's treatments could be effective for multiple myeloma?

Research has shown that using daratumumab with clarithromycin, pomalidomide, and dexamethasone, which participants in this trial will receive, can effectively treat relapsed or hard-to-treat multiple myeloma. Studies have found that combining daratumumab with pomalidomide and dexamethasone leads to better response rates than some other treatments. Specifically, previous patients experienced improved management of their condition with this combination. Daratumumab is already known to effectively treat multiple myeloma, helping many patients manage their disease better. This combination aims to build on those successes, seeking even better results. ^{1 2 3 5 6}

Who Is on the Research Team?

Cara Rosenbaum, MD

Principal Investigator

Weill Medical College of Cornell University

Are You a Good Fit for This Trial?

This trial is for adults with Multiple Myeloma that has come back or hasn't responded to treatment. They must have measurable disease, be able to take aspirin, and not be pregnant or breastfeeding. Participants should be in decent physical shape (ECOG 0-2) and expected to live more than 3 months. They can't join if they've had certain treatments recently, other cancers, severe illnesses that could affect the study, allergies to the drugs used in this trial, or some heart/lung conditions.

Inclusion Criteria

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

You must be expected to live for more than 3 months.

My myeloma has returned or is not responding to treatment.

Exclusion Criteria

I have had nerve pain, blood clots, or neuropathy recently.

I have not taken certain medications recently.

I am not pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive daratumumab, clarithromycin, pomalidomide, and dexamethasone for 8 cycles until progressive disease or unacceptable toxicity

8 months

Weekly visits for Cycles 1-2, bi-weekly for Cycles 3-6, monthly for Cycles 7-8

Maintenance

Participants continue treatment with daratumumab, pomalidomide, and dexamethasone for up to 24 cycles

Up to 2 years

Monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Clarithromycin
• Daratumumab
• Dexamethasone
• Pomalidomide

Trial Overview The study tests a combination therapy called D-ClaPd on patients who've previously been treated with Daratumumab. It's a phase II trial where participants receive Daratumumab subcutaneously along with Clarithromycin/Pomalidomide/Dexamethasone until their disease progresses or side effects become too much.

How Is the Trial Designed?

Group I: daratumumab/clarithromycin/pomalidomide/dexamethasone Experimental Treatment 4 Interventions

Induction Phase: 8 cycles (cycle length of 28 days) * Daratumumab SC: 1800mg SC weekly for 8 weeks for Cycle 1 and 2 1800mg SC every 2 weeks on Day 1 and 15 for Cycle 3-6 1800mg SC every 4 weeks on Day 1 for Cycle 7-8 * Clarithromycin 500mg PO BID until VGPR or 8 cycles, whichever occurs first * Pomalidomide 4mg PO on Days 1-21 * Dexamethasone 20mg IV as pre-medication on Day 1, 8 40mg PO on the day after daratumumab for Cycle 1 Days 15 and 22 40mg PO pre-daratumumab weekly for Cycle 2-6 20mg PO pre-daratumumab weekly for Cycle 7-8 Maintenance Phase (Cycle 9+): Up to 24 cycles (cycle length of 28 days) * Daratumumab 1800 mg SC on Day 1 * Pomalidomide 4mg PO on Day 1-21 * Dexamethasone 20mg PO pre-daratumumab weekly for Cycles 9 and beyond

Clarithromycin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Biaxin for:

• Acute maxillary sinusitis
• Acute otitis media
• Community-acquired pneumonia
• Uncomplicated skin and skin structure infections
• Helicobacter pylori eradication
• Mycobacterium avium complex (MAC) infection

Approved in European Union as Klaricid for:

• Acute bacterial exacerbation of chronic bronchitis
• Community-acquired pneumonia
• Uncomplicated skin and skin structure infections
• Helicobacter pylori eradication
• Mycobacterium avium complex (MAC) infection

Approved in Canada as Biaxin for:

• Acute maxillary sinusitis
• Acute otitis media
• Community-acquired pneumonia
• Uncomplicated skin and skin structure infections
• Helicobacter pylori eradication
• Mycobacterium avium complex (MAC) infection

Who Is Running the Clinical Trial?

Weill Medical College of Cornell University

Lead Sponsor

Trials

1,103

Recruited

1,157,000+

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Joaquin Duato

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2022

MBA from ESADE, Master of International Management from Thunderbird School of Global Management

Dr. Jijo James, MD

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2014

MD from St. Johns Medical College, MPH from Columbia University

Published Research Related to This Trial

In a study of 141 patients receiving daratumumab for multiple myeloma, 33% experienced infusion-related reactions (IRRs) during their first infusion.

The addition of montelukast to the standard premedication regimen significantly reduced the incidence of IRRs, with only 27% of patients receiving montelukast experiencing reactions compared to 45% of those who did not (P = .0371).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Montelukast for the Prevention of Infusion-related Reactions With Daratumumab. Moore, DC., Arnall, JR., Thompson, DL., et al.[2021]

The BLT-D regimen, which combines clarithromycin, low-dose thalidomide, and dexamethasone, showed a high response rate of 93% in 50 patients with multiple myeloma, indicating its efficacy as a treatment option.

While the treatment was generally well-tolerated, neurotoxicity was the main reason for discontinuation, and caution is advised for patients with existing health issues like severe cardiopulmonary disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

BLT-D (clarithromycin [Biaxin], low-dose thalidomide, and dexamethasone) for the treatment of myeloma and Waldenström's macroglobulinemia. Coleman, M., Leonard, J., Lyons, L., et al.[2022]

Daratumumab combined with lenalidomide and dexamethasone showed an impressive overall response rate of 81% in patients with relapsed/refractory multiple myeloma, indicating its efficacy in this challenging patient population.

The treatment was well tolerated, with no dose-limiting toxicities observed and manageable infusion-related reactions, suggesting a favorable safety profile consistent with previous treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Plesner, T., Arkenau, HT., Gimsing, P., et al.[2022]

In a phase II study involving 30 patients with relapsed and refractory myeloma, a combination of clarithromycin, low-dose thalidomide, and low-dose dexamethasone was well tolerated and effective, with a 96% overall response rate.

The combination therapy led to high response rates, with 89% of patients achieving at least a 50% reduction in paraprotein levels, demonstrating that this approach allows for lower and more tolerable doses of the medications while still providing significant clinical benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clarithromycin with low dose dexamethasone and thalidomide is effective therapy in relapsed/refractory myeloma. Morris, TC., Kettle, PJ., Drake, M., et al.[2022]

Daratumumab significantly improves overall survival (OS) compared to pomalidomide plus low-dose dexamethasone in patients with heavily pretreated multiple myeloma, with hazard ratios indicating a strong treatment benefit (0.56 and 0.51 for two different studies).

The survival advantage of daratumumab is even more pronounced in patients who have not previously been treated with pomalidomide, suggesting it may be particularly effective in this subgroup.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative Efficacy of Daratumumab Monotherapy and Pomalidomide Plus Low-Dose Dexamethasone in the Treatment of Multiple Myeloma: A Matching Adjusted Indirect Comparison. Van Sanden, S., Ito, T., Diels, J., et al.[2019]

Daratumumab is a monoclonal antibody that effectively targets CD38 on multiple myeloma cells, leading to cell death through various mechanisms such as complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity.

It has shown a favorable safety profile and significant clinical activity as both a standalone treatment and in combination with lenalidomide for patients with relapsed multiple myeloma who have not responded to other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. Xia, C., Ribeiro, M., Scott, S., et al.[2018]

Intravenous daratumumab, when combined with bortezomib, thalidomide, and dexamethasone, significantly improves treatment outcomes for adults with newly diagnosed multiple myeloma, leading to higher rates of stringent complete response and prolonged progression-free survival, as shown in the phase III CASSIOPEIA trial.

The addition of daratumumab has a minimal impact on overall toxicity, with the most common serious side effects being blood-related issues, indicating it is a relatively safe option for patients undergoing treatment for multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Eligible Newly Diagnosed Multiple Myeloma. Lamb, YN.[2021]

Intravenous daratumumab, when combined with bortezomib, melphalan, and prednisone, significantly improves progression-free survival in patients with newly diagnosed multiple myeloma who cannot undergo autologous stem cell transplantation, as shown in the phase 3 ALCYONE trial.

The addition of daratumumab does not increase overall toxicity compared to the standard treatment, although it may lead to more infusion-related reactions and infections, making it a promising and relatively safe treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Combination Therapy for Transplant-Ineligible Newly Diagnosed Multiple Myeloma. Syed, YY.[2021]

In a phase 3 trial involving 304 patients with relapsed or refractory multiple myeloma, the combination of daratumumab with pomalidomide and dexamethasone significantly improved progression-free survival compared to pomalidomide and dexamethasone alone, with a median of 12.4 months versus 6.9 months.

While the combination treatment was effective, it was associated with a higher incidence of grade 3 or 4 adverse events, particularly neutropenia, indicating that while daratumumab enhances treatment efficacy, it may also increase the risk of serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial. Dimopoulos, MA., Terpos, E., Boccadoro, M., et al.[2021]

In a subgroup analysis of the CASTOR trial involving 498 patients, daratumumab combined with bortezomib and dexamethasone (D-Vd) significantly prolonged progression-free survival (PFS) in patients with high cytogenetic risk (12.6 months) compared to bortezomib and dexamethasone alone (6.2 months).

D-Vd also demonstrated a higher rate of minimal residual disease (MRD) negativity, indicating deeper responses in treatment effectiveness, while maintaining a safety profile consistent with the overall study population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. Weisel, K., Spencer, A., Lentzsch, S., et al.[2021]

In a study of 103 patients with relapsed/refractory multiple myeloma, the combination of daratumumab, pomalidomide, and dexamethasone showed an overall response rate of 60%, indicating significant efficacy even in patients with a history of multiple prior therapies.

The safety profile of this combination treatment was similar to pomalidomide and dexamethasone alone, with the main exception being a higher incidence of neutropenia and infusion-related reactions, but without an increase in infection rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Chari, A., Suvannasankha, A., Fay, JW., et al.[2022]

Citations

1. bloodcancerunited.org bloodcancerunited.org/resources/newsroom/fda-approval-new-treatment-indication-multiple-myeloma-drug

New Treatment Indication for Multiple Myeloma Drug The most common adverse drug reactions in patients treated with daratumumab plus hyaluronidase were fatigue, pneumonia, upper respiratory tract infection and ...

2. darzalex.com darzalex.com/

Official Consumer Website | DARZALEX® & DARZALEX ... Be heard in the face of a multiple myeloma diagnosis or a relapse. Ask your doctor if DARZALEX FASPRO or DARZALEX is right for you.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9400732/

The evolving role and utility of off-label drug use in multiple ... Daratumumab plus pomalidomide and dexamethasone ... Phase 2 study of clarithromycin, pomalidomide, and dexamethasone in relapsed or refractory multiple myeloma.

4. cancer.gov cancer.gov/news-events/cancer-currents-blog/2025/fda-daratumumab-isatuximab-newly-diagnosed-myeloma

Darzalex Faspro, Sarclisa Approvals for Multiple Myeloma Two recent approvals by the Food and Drug Administration (FDA) broaden the initial treatment options for people who have a new diagnosis of multiple myeloma.

5. myeloma.org myeloma.org/darzalex-daratumumab

Darzalex (Daratumumab) Darzalex (daratumumab) is a highly effective drug used to treat multiple myeloma. Read about who is a candidate, side effects, special warnings.

6. jnj.com jnj.com/media-center/press-releases/european-commission-approves-darzalex-daratumumab-as-the-first-licensed-treatment-for-patients-with-high-risk-smouldering-multiple-myeloma

European Commission approves DARZALEX® ... Median time to first-line multiple myeloma treatment was not reached for patients receiving daratumumab SC compared to 50.2 months with active ...