Quad Therapy for Multiple Myeloma

No longer recruiting at 3 trial locations

Overseen By Caitlin Costello, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Diego

Must be taking: Aspirin, Warfarin, Heparin

Must not be taking: Strong CYP3A inducers

Disqualifiers: HIV, Hepatitis, Heart failure, 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: 8

Duration: 16 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination of four drugs—Daratumumab (Darzalex), Ixazomib, Pomalidomide, and Dexamethasone—to evaluate their effectiveness in treating Multiple Myeloma, a type of blood cancer. The goal is to determine how many patients respond positively to this treatment mix. Suitable candidates for this trial include those diagnosed with Multiple Myeloma who have undergone one to three previous treatments and have experienced a return or worsening of the disease. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

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 strong medications like rifampin 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 combining the drugs daratumumab, ixazomib, pomalidomide, and dexamethasone has promising safety results for treating multiple myeloma. The FDA has already approved these medicines for this condition, and they have been used together in various ways.

Studies have linked daratumumab to common side effects such as tiredness, pneumonia, and upper respiratory infections, which can be managed with medical care. Ixazomib and pomalidomide are also widely used and generally well-tolerated, though they might cause low blood counts or nausea.

Overall, this treatment combination aims to be effective, but it can have side effects that should be discussed with a healthcare provider. The current trial examines patient response to the treatment, with safety being closely monitored. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the quad therapy for multiple myeloma because it combines four powerful drugs—daratumumab, dexamethasone, ixazomib, and pomalidomide—each bringing unique strengths to the table. Unlike standard treatments that use these drugs separately, this combination leverages daratumumab's ability to target and destroy cancer cells, pomalidomide's immune-boosting effects, and ixazomib's role in disrupting cancer cell survival. This multi-faceted approach could potentially enhance treatment effectiveness and offer new hope for patients by addressing the disease from multiple angles simultaneously.

What evidence suggests that this trial's treatments could be effective for Multiple Myeloma?

Research has shown that a combination of four drugs—Daratumumab, Ixazomib, Pomalidomide, and Dexamethasone—may be promising for treating Multiple Myeloma. Participants in this trial will receive this combination therapy. Daratumumab, when used with other drugs, is approved for newly diagnosed patients and has slowed the disease. Patients who have used similar drug combinations in the past have experienced positive results. This suggests that this treatment could effectively manage Multiple Myeloma by attacking cancer cells in different ways. The goal of this combination is to improve patient outcomes by enhancing the effectiveness of each drug. ^{3 5 6 7 8}

Who Is on the Research Team?

Caitlin Costello, MD

Principal Investigator

University of California, San Diego

Are You a Good Fit for This Trial?

This trial is for adults with Multiple Myeloma who've had 1-3 prior treatments but haven't used Daratumumab or Ixazomib before. They must not be pregnant, agree to birth control measures, and join the POMALYST REMS program. Participants should have a life expectancy over 3 months, an ECOG status of 0-2, and adequate organ function.

Inclusion Criteria

My liver is working well.

I agree to use two forms of birth control or abstain from sex for 120 days after the last dose.

I agree to take daily aspirin or, if I have a history of blood clots, to be on full anticoagulation treatment.

Exclusion Criteria

My condition did not improve after taking pomalidomide.

I have previously used daratumumab or ixazomib.

I am HIV positive or suspected to be.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Daratumumab, Ixazomib, Pomalidomide, and Dexamethasone as salvage therapy

16 weeks

Weekly visits for 8 weeks, biweekly for 8 weeks, then monthly

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Long-term follow-up

Participants are monitored for progression-free survival and overall survival

Up to 100 months

What Are the Treatments Tested in This Trial?

Interventions

• Daratumumab
• Dexamethasone
• Ixazomib
• Pomalidomide

Trial Overview The study tests a combination therapy using Daratumumab, Ixazomib, Pomalidomide, and Dexamethasone in patients with relapsed/refractory Multiple Myeloma. It aims to evaluate the overall response rate to this salvage therapy regimen.

How Is the Trial Designed?

Group I: ixazomib, daratumumab, pomalidomide and dexamethasone Experimental Treatment 4 Interventions

Daratumumab will be administered at 16mg/kg IV weekly x 8 weeks, biweekly x 8 weeks, then monthly. Pomalidomide 4mg will be administered orally daily for days 1-21. Patients ≤ age 75 will receive a 40mg dose of dexamethasone, and those over the age of 75 may receive a 20mg dose of dexamethasone orally on days 1, 8, 15, and 22 (weekly). Ixazomib will be administered 4mg orally on days 1, 8 and 15.

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?

University of California, San Diego

Lead Sponsor

Trials

1,215

Recruited

1,593,000+

Celgene

Industry Sponsor

Trials

649

Recruited

130,000+

Top Products

>- **Revlimid (lenalidomide)**: Multiple myeloma, myelodysplastic syndromes, and mantle cell lymphoma treatment. - **Pomalyst (pomalidomide)**: Relapsed/refractory multiple myeloma treatment. - **Otezla (apremilast)**: Psoriatic arthritis treatment. - **Thalomid (thalidomide)**: Erythema nodosum leprosum and multiple myeloma treatment.

Jay Backstrom

Celgene

Chief Medical Officer since 2016

MD

Mark Alles

Celgene

Chief Executive Officer since 2016

Bachelor's degree from Lock Haven University of Pennsylvania

Takeda

Industry Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

Janssen, LP

Industry Sponsor

Trials

169

Recruited

329,000+

Founded

1953

Headquarters

Beerse, Belgium

Known For

Mental Health Therapies

Top Products

Imodium, Remicade, Invega, Procrit

Joaquin Duato

Janssen, LP

Chief Executive Officer since 2022

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

Dr. Jijo James, MD

Janssen, LP

Chief Medical Officer since 2014

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

Published Research Related to This Trial

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 phase II study involving 65 intermediate-fit patients with newly diagnosed multiple myeloma, the combination of Ixazomib, Daratumumab, and low-dose dexamethasone resulted in a 71% overall response rate during induction therapy, indicating its efficacy as a first-line treatment.

While the treatment improved global quality of life significantly, it also led to frequent dose modifications due to low-grade polyneuropathy, suggesting that the regimen's long-term tolerability may be a concern for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixazomib, daratumumab and low-dose dexamethasone in intermediate-fit patients with newly diagnosed multiple myeloma: an open-label phase 2 trial. Groen, K., Stege, CAM., Nasserinejad, K., et al.[2023]

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]

In a study comparing two induction therapies for newly diagnosed multiple myeloma, the quadruplet regimen (D-VTd) showed significantly better response rates after treatment, with 90.5% achieving complete remission (CR) or stringent complete remission (sCR) compared to 68.6% in the triplet regimen (VRd).

The quadruplet regimen (D-VTd) also resulted in a higher rate of very good partial response (VGPR or better) at 93%, compared to 67.6% in the triplet regimen (VRd), although VRd was associated with a higher incidence of skin rash.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advantage of achieving deep response following frontline daratumumab-VTd compared to VRd in transplant-eligible multiple myeloma: multicenter study. Byun, JM., Park, SS., Yoon, SS., et al.[2023]

In a study of 90 patients with relapsed/refractory multiple myeloma, the combination of ixazomib, thalidomide, and dexamethasone showed a 51.1% overall response rate, indicating significant efficacy in treating this condition.

The treatment was well tolerated, with rare occurrences of severe toxicities, and ixazomib maintenance therapy improved response depth in 12.4% of patients, suggesting a beneficial long-term effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixazomib-Thalidomide-Dexamethasone for induction therapy followed by Ixazomib maintenance treatment in patients with relapsed/refractory multiple myeloma. Ludwig, H., Poenisch, W., Knop, S., et al.[2021]

In a phase I/II study involving 29 patients with lenalidomide and proteasome inhibitor-refractory multiple myeloma, the combination of ixazomib, pomalidomide, and dexamethasone showed a promising overall response rate of 51.7% and a median duration of response of 16.8 months.

The treatment was generally well-tolerated, with common side effects aligning with those expected from the individual drugs, suggesting that this all-oral regimen warrants further investigation in relapsed/refractory multiple myeloma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I/II study of ixazomib, pomalidomide, and dexamethasone for lenalidomide and proteasome inhibitor refractory multiple myeloma (Alliance A061202). Voorhees, PM., Suman, VJ., Tuchman, SA., 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]

Lenalidomide combined with dexamethasone has been shown to be effective for treating relapsed/refractory multiple myeloma, and it has received approval from both the FDA and EMA for patients who have undergone at least one prior therapy.

The most common serious side effects include cytopenias and infections, but an expert panel has provided management strategies to minimize these risks, ensuring that patients can receive the full benefits of the treatment without unnecessary dose reductions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma. Palumbo, A., Dimopoulos, M., San Miguel, J., et al.[2018]

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/dvrd/

DARZALEX & DARZALEX FASPRO® (daratumumab and ... An FDA-approved treatment combination for patients who are newly diagnosed with multiple myeloma and eligible to receive a stem cell transplant.

3. jnjmedicalconnect.com jnjmedicalconnect.com/products/darzalex-faspro/medical-content/use-of-darzalex-darzalex-faspro-in-combination-with-ixazomib-in-multiple-myeloma

DARZALEX FASPRO® (daratumumab and hyaluronidase- ... A summary of all available data regarding DARZALEX® (daratumumab) and DARZALEX FASPRO® (daratumumab and hyaluronidase) use in combination ...

4. myeloma.org myeloma.org/news-events/multiple-myeloma-news/phase-3-majestec-3-tecvayli-darzalex-results

Phase 3 MajesTEC-3 Results: Tecvayli-Darzalex Faspro ... At follow-up after almost three years, treatment with TECVAYLI and DARZALEX FASPRO showed significant delayed progression of multiple myeloma ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT03590652

Study Details | NCT03590652 | Daratumumab, Ixazomib, ... The purpose of this study is to determine the overall response rate of patients with Multiple Myeloma to the combination of Daratumumab, Ixazomib, Pomalidomide ...

6. darzalex.com darzalex.com/

Official Consumer Website | DARZALEX® & DARZALEX ... Learn about adult treatment with DARZALEX® and DARZALEX FASPRO®. See Full Prescribing & Safety Information.

7. 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 ...

8. myeloma.org myeloma.org/multiple-myeloma-drugs

Multiple Myeloma Drugs: Types, Classes & Treatments This list of current FDA-approved multiple myeloma drugs is organized by drug class, with a guide to the generic and brand names for each medication.