Daratumumab Combo for Multiple Myeloma

Recruiting in Palo Alto (17 mi)

Overseen by Cara Rosenbaum, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a new combination of four drugs for patients with multiple myeloma who did not respond to previous treatments. The drugs work together to boost the immune system, fight infections, reduce inflammation, and directly target cancer cells.

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.

What data supports the effectiveness of the drug combination Daratumumab, Clarithromycin, Dexamethasone, and Pomalidomide for treating multiple myeloma?

Research shows that combining daratumumab with pomalidomide and dexamethasone leads to a 60% overall response rate in patients with relapsed or refractory multiple myeloma. Additionally, a combination of clarithromycin, thalidomide, and dexamethasone achieved a 96% overall response rate in similar patients, suggesting that these combinations can be effective in treating multiple myeloma. ^{1 2 3 4 5}

What is the safety profile of the Daratumumab combination treatment for multiple myeloma?

The combination of Daratumumab with other drugs like pomalidomide and dexamethasone has been generally well-tolerated in patients with multiple myeloma. Common side effects include infusion-related reactions, which are most frequent during the first infusion, and blood-related issues like neutropenia (low white blood cell count), anemia (low red blood cell count), and leukopenia (low white blood cell count). These side effects are consistent with those seen in the individual therapies. ^{5 6 7 8 9}

What makes the Daratumumab Combo for Multiple Myeloma drug unique?

The Daratumumab Combo for Multiple Myeloma is unique because it combines daratumumab, a monoclonal antibody targeting CD38 on myeloma cells, with clarithromycin, pomalidomide, and dexamethasone, offering a novel approach by leveraging multiple mechanisms to kill cancer cells and modulate the immune system, potentially improving outcomes for patients who have already tried other treatments. ^{2 6 7 10 11}

Research Team

Cara Rosenbaum, MD

Principal Investigator

Weill Medical College of Cornell University

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Clarithromycin (Other)
• Daratumumab (Monoclonal Antibodies)
• Dexamethasone (Corticosteroid)
• Pomalidomide (Other)

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.

Participant Groups

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 Canada for the following indications:

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+

Dr. Robert Min

Weill Medical College of Cornell University

Chief Executive Officer since 2024

MD, MBA

Dr. Adam R. Stracher

Weill Medical College of Cornell University

Chief Medical Officer since 2024

MD

Janssen Scientific Affairs, LLC

Industry Sponsor

Trials

165

Recruited

579,000+

Ricardo Attar

Janssen Scientific Affairs, LLC

Chief Executive Officer since 2008

PhD in Molecular Biology, University of Buenos Aires

Dr. Anastasia G. Daifotis

Janssen Scientific Affairs, LLC

Chief Medical Officer since 2023

MD

Findings from Research

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]

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]

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]

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 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]

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, 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Clarithromycin with low dose dexamethasone and thalidomide is effective therapy in relapsed/refractory myeloma. [2022]

2. England 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. [2021]

3. England pubmed.ncbi.nlm.nih.gov

Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

BLT-D (clarithromycin [Biaxin], low-dose thalidomide, and dexamethasone) for the treatment of myeloma and Waldenström's macroglobulinemia. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. [2022]

6. New Zealand pubmed.ncbi.nlm.nih.gov

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

7. United States pubmed.ncbi.nlm.nih.gov

Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. [2022]

8. England 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. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Evaluation of Montelukast for the Prevention of Infusion-related Reactions With Daratumumab. [2021]

10. Spain pubmed.ncbi.nlm.nih.gov

Daratumumab: monoclonal antibody therapy to treat multiple myeloma. [2018]

11. New Zealand pubmed.ncbi.nlm.nih.gov

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