DPd for Amyloidosis

Not currently recruiting at 3 trial locations

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: Non-AL amyloidosis, Myeloma, Cardiac disease, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of drugs—daratumumab (Darzalex), pomalidomide, and dexamethasone—to determine if it can help more people with relapsed or stubborn amyloidosis achieve complete remission. The study targets patients previously treated with daratumumab. It may suit those with primary AL amyloidosis who have tried daratumumab before and have no severe heart or lung conditions. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Will I have to stop taking my current medications?

The trial protocol 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.

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

Research has shown that the combination of daratumumab, pomalidomide, and dexamethasone (DPd) has been tested for safety in people with multiple myeloma and light chain amyloidosis. A large study involving 1,249 patients with these conditions found the treatment to be generally well-tolerated, with most patients not experiencing severe side effects.

Common side effects included tiredness, nausea, and low blood counts, but these were manageable and often temporary. Daratumumab, a key component of this treatment, is already approved for treating light chain amyloidosis, which supports its safety profile.

While no treatment is without risk, current data indicate that the DPd combination has been used safely in many patients. Those considering joining a clinical trial for this treatment can find reassurance in the existing safety data. However, discussing potential risks with a healthcare provider remains important. ^{1 2 3 4 5}

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

Unlike the standard treatments for amyloidosis, which often involve chemotherapy and stem cell transplants, the combination of Daratumumab, Pomalidomide, and Dexamethasone offers a targeted approach. Daratumumab is a monoclonal antibody that specifically targets CD38 on plasma cells, potentially reducing amyloid production without the widespread side effects of traditional chemotherapy. Additionally, this regimen is notable for its subcutaneous administration of Daratumumab, which can be more convenient and less invasive than intravenous options. Researchers are excited about this combination because it could offer a more tailored and less toxic treatment option, potentially improving outcomes for patients with amyloidosis.

What evidence suggests that this treatment might be an effective treatment for amyloidosis?

This trial will evaluate the combination of daratumumab, pomalidomide, and dexamethasone for treating amyloidosis. Studies have shown that this combination can effectively treat conditions like multiple myeloma and amyloidosis. Daratumumab, in particular, has approval for treating newly diagnosed light chain amyloidosis, especially when combined with other medications. Specifically, research indicates that more than half of the patients who received this combination experienced long-term disease control. These findings suggest that this treatment could benefit patients with amyloidosis that has returned or not responded to previous treatments, especially those who have used daratumumab before. ^{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 patients with relapsed/refractory light chain amyloidosis who have previously been treated with daratumumab. They should be relatively healthy (performance status 0-2), have normal liver function, stable kidney function, and acceptable blood counts. Patients must not have non-AL amyloidosis, serious infections, significant heart disease, or recent major surgery.

Inclusion Criteria

Able to give voluntary written consent

You need to have a certain level of white blood cells and platelets in your blood.

I took pomalidomide, improved, and didn't worsen within 60 days after the last dose.

Exclusion Criteria

My condition is active multiple myeloma.

You have HIV, hepatitis B, or hepatitis C.

I haven't needed IV antibiotics for an infection in the last 14 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive daratumumab, pomalidomide, and dexamethasone (DPd) therapy. Pomalidomide is administered orally on days 1-21 of a 28-day cycle. Dexamethasone is given as premedication and on specific days depending on the cycle. Daratumumab is administered subcutaneously weekly for 8 weeks, then every 2 weeks during induction, and every 4 weeks during maintenance.

6 months

Weekly visits initially, then bi-weekly and monthly

Follow-up

Participants are monitored for safety and effectiveness after treatment, with a focus on hematologic and organ response rates.

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab
• Dexamethasone
• Pomalidomide

Trial Overview The study is testing a combination therapy of Daratumumab SC (subcutaneous injection), Pomalidomide, and Dexamethasone in patients who've had Daratumumab before. It aims to see if this combo increases complete remission rates compared to previous treatments with pomalidomide/dexamethasone alone.

How Is the Trial Designed?

Group I: daratumumab/pomalidomide/dexamethasone Experimental Treatment 3 Interventions

Pomalidomide: (4mg orally) on days 1-21 of a 28-day cycle Dexamethasone: * 20mg IV as premedication on days 1, 8, 15, and 22 * 20mg orally the day after daratumumab dosing for cycles 1-2 of induction * 40mg IV as premedication on days 1 and 15 on daratumumab treatment days * 40mg orally on non-daratumumab days (8 and 15) for cycles 3-6 * 20mg on day 1 of every cycle as premedication on daratumumab dosing day 1 in maintenance cycles (cycles 7 and beyond) * If you are a subject age 70 and older, the dexamethasone dosing will be reduced by 50% at the time of induction. Daratumumab: * 1800mg sub-cutaneously weekly x8 weeks * 1800mg sub-cutaneously every 2 weeks during induction (cycles 3-6) * 1800mg sub-cutaneously every 4 weeks cycles 7 and beyond

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

Approved in European Union as Darzalex for:

• Relapsed and refractory multiple myeloma
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone

Approved in United States as Darzalex for:

• Multiple myeloma in patients who have received at least three prior therapies
• Newly diagnosed multiple myeloma in combination with bortezomib, melphalan, and prednisone
• Relapsed or refractory multiple myeloma in combination with lenalidomide and dexamethasone

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 21 patients with light chain amyloidosis treated with daratumumab, bortezomib, and limited-duration dexamethasone (Dara-Vd), 90% achieved a hematologic response, indicating the regimen's high efficacy, especially in patients with significant organ dysfunction.

Dara-Vd was well-tolerated and resulted in rapid responses, with a median time to response of just 11 days, and a 1-year overall survival rate of 76%, demonstrating its potential as a frontline treatment option for patients who may not tolerate more intensive therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab Plus Bortezomib and Dexamethasone in Newly Diagnosed Systemic Light Chain Amyloidosis. Kennedy, VE., Natsuhara, K., Maringanti, SA., et al.[2023]

In a phase 1/2 trial involving 27 patients with light chain amyloidosis, pomalidomide combined with dexamethasone was found to be safe, with a maximum tolerated dose established at 4 mg, despite some patients experiencing significant side effects like myelosuppression and fatigue.

The treatment resulted in a 50% hematologic response rate among evaluable patients, with responses typically peaking after 3 cycles and lasting an average of 15 months, indicating promising efficacy for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 1 and 2 trial. Sanchorawala, V., Shelton, AC., Lo, S., et al.[2021]

In a safety run-in of the ANDROMEDA study involving 28 patients with newly diagnosed AL amyloidosis, the combination of daratumumab and CyBorD showed a high overall hematologic response rate of 96%, with 54% achieving a complete response.

The treatment was well tolerated, with minimal adverse events and no new safety concerns compared to the intravenous formulation, indicating its potential as a safe and effective option for patients with AL amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. Palladini, G., Kastritis, E., Maurer, MS., et al.[2021]

A 43-year-old female patient with severe light-chain amyloidosis and multiple myeloma showed significant improvement after switching to a treatment regimen of daratumumab, pomalidomide, and dexamethasone (DaraPomD), achieving an amyloid complete-hematologic response after just two cycles.

The treatment was well tolerated and did not worsen her heart failure symptoms, suggesting that DaraPomD could be a promising option for patients with severe AL amyloidosis, warranting further clinical trials to evaluate its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab, pomalidomide, and dexamethasone as a bridging therapy to autologous stem cell transplantation in a case of systemic light-chain amyloidosis with advanced cardiac involvement. Arnall, JR., Usmani, SZ., Adamu, H., et al.[2019]

The combination therapy of daratumumab, cyclophosphamide, bortezomib, and dexamethasone (daratumumab-CyBorD) has become the new standard-of-care for systemic light chain (AL) amyloidosis, showing high rates of hematologic and organ response.

Recent advancements in patient selection and induction regimens have significantly reduced the mortality associated with autologous stem cell transplant (ASCT), while new treatments like venetoclax are proving effective for patients with specific genetic abnormalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in the treatment of light chain amyloidosis. Palladini, G., Milani, P.[2023]

In a phase 2 trial involving 33 patients with previously treated AL amyloidosis, the combination of pomalidomide and dexamethasone showed a confirmed hematologic response rate of 48%, indicating its efficacy in this rare condition.

The treatment resulted in a median overall survival of 28 months and a progression-free survival of 14 months, suggesting that pomalidomide could be a valuable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Dispenzieri, A., Buadi, F., Laumann, K., et al.[2022]

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]

In the phase III ANDROMEDA trial, subcutaneous daratumumab combined with bortezomib, cyclophosphamide, and dexamethasone significantly improved the rate of complete hematological response in patients with newly diagnosed systemic AL amyloidosis compared to the standard treatment alone.

This combination therapy not only produced rapid and deep responses but also resulted in better progression-free survival and higher rates of cardiac and renal responses at 6 and 12 months, while maintaining an acceptable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Daratumumab: A Review in Newly Diagnosed Systemic Light Chain Amyloidosis. Blair, HA.[2022]

In a study of 72 previously treated patients with multiple myeloma and AL amyloidosis, daratumumab showed a high efficacy, with 82% of patients achieving a hematologic response after eight infusions, including 16% complete responses and 42% very good partial responses.

Daratumumab also demonstrated notable renal responses in 60% of patients and cardiac responses in 29%, indicating its potential as an effective treatment option for patients with relapsed/refractory AL amyloidosis, especially those with high plasma cell burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High rate of profound clonal and renal responses with daratumumab treatment in heavily pre-treated patients with light chain (AL) amyloidosis and high bone marrow plasma cell infiltrate. Milani, P., Fazio, F., Basset, M., et al.[2020]

In a study of 97 patients with relapsed/refractory multiple myeloma treated with daratumumab, pomalidomide, and dexamethasone (DPd), the overall response rate was 74%, indicating that this treatment is effective for many patients.

However, a significant risk of hematological toxicities was observed, with 79% of responders experiencing neutropenia and 65% leukopenia, leading to a high incidence of dose reductions or treatment interruptions (76%) and increased hospitalization due to complications like pneumonia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse Hematological and Non-Hematological Events in Patients With Relapsed/Refractory Multiple Myeloma That Are Responsive to Daratumumab, Pomalidomide and Dexamethasone. Alkharabsheh, O., Bellman, P., Mahmoudjafari, Z., et al.[2023]

Citations

1. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex-faspro/medical-content/use-of-darzalex-darzalex-faspro-in-combination-with-pomalidomide-and-dexamethasone-in-multiple-myel

DARZALEX FASPRO® (daratumumab and hyaluronidase- ... Outcomes of daratumumab, pomalidomide, and dexamethasone, followed by high-dose chemotherapy and autologous stem cell transplantation, in ...

2. jnj.com jnj.com/media-center/press-releases/darzalex-faspro-daratumumab-and-hyaluronidase-fihj-based-regimen-shows-95-percent-progression-free-survival-at-four-years-in-transplant-eligible-newly-diagnosed-patients-with-multiple-myeloma-who-achieved-sustained-mrd-negativity

DARZALEX FASPRO® (daratumumab and hyaluronidase ... More than half of patients who received the DARZALEX FASPRO®-based regimen achieved sustained MRD negativity for 24 or more months and more than ...

3. aetna.com aetna.com/cpb/medical/data/900_999/0904.html?ref=counterforcehealth.org

Daratumumab (Darzalex) and Daratumumab and ... Darzalex Faspro is indicated for the treatment of adult patients with newly diagnosed light chain amyloidosis in combination with bortezomib, cyclophosphamide ...

4. mayoclinic.org mayoclinic.org/drugs-supplements/daratumumab-and-hyaluronidase-fihj-subcutaneous-route/description/drg-20489593

Daratumumab and hyaluronidase-fihj (subcutaneous route) Daratumumab and hyaluronidase-fihj combination injection is used together with bortezomib, melphalan, and prednisone to treat newly diagnosed multiple myeloma.

5. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/761145s009lbl.pdf

Darzalex Faspro - accessdata.fda.gov In Combination with Pomalidomide and Dexamethasone. The efficacy of DARZALEX FASPRO with pomalidomide and dexamethasone (DARZALEX. FASPRO-Pd) versus ...

6. darzalexhcp.com darzalexhcp.com/indications-and-dosing/

Indications & Dosing In a pooled safety population of 1249 patients with multiple myeloma (N=1056) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as ...