Daratumumab + Bortezomib/Dexamethasone & Ixazomib for Multiple Myeloma

Overseen By Hans Lee

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: CYP3A inducers, St. John's wort

Disqualifiers: COPD, Cardiac issues, Active infections, 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: 30

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of treatments to assess their effectiveness in helping people with multiple myeloma, a type of blood cancer that has returned or is unresponsive to current treatments. The study combines immunotherapy with monoclonal antibodies like daratumumab (Darzalex), which may enhance the immune system's ability to fight cancer, and chemotherapy drugs like dexamethasone, which inhibit cancer cell growth. It also includes bortezomib (Velcade) and ixazomib (Ninlaro), which can block enzymes necessary for cancer cell growth. Individuals with multiple myeloma that has relapsed or is refractory after recent treatments, and who have had at least a partial response to one previous treatment, might be suitable candidates for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Do I have to stop taking my current medications to join the trial?

The trial requires that you stop certain medications before starting. You must not take strong CYP3A inducers (like rifampin or St. John's wort) within 14 days before starting, and you must complete any recent chemotherapy or antibody therapy within specific timeframes before the trial begins. If you're on corticosteroids, you need to stop them at least 14 days before starting, except for low doses or short emergency use.

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

Research has shown that a combination of the drugs daratumumab, bortezomib, dexamethasone, and ixazomib has been studied for treating multiple myeloma, a type of blood cancer. The FDA has already approved daratumumab for use with other drugs like bortezomib and dexamethasone in treating multiple myeloma, suggesting it is generally safe.

Studies have found that bortezomib, especially when injected under the skin, usually causes less nerve damage than other methods. Common side effects might include fatigue and low blood cell counts, but these can often be managed.

Dexamethasone, a steroid commonly used in cancer treatment, can cause side effects like mood changes and higher blood sugar levels, but these are known and can often be controlled with monitoring.

While detailed safety data from specific study phases isn't available, the FDA's approval of similar drug combinations suggests they are reasonably safe. Patients considering joining the trial should discuss any concerns and possible side effects with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for multiple myeloma because it combines daratumumab with bortezomib, dexamethasone, and ixazomib, offering a multi-faceted approach to the disease. Unlike most treatments that rely on one or two drugs, this regimen uses daratumumab, a monoclonal antibody that targets CD38 on myeloma cells, alongside proteasome inhibitors like bortezomib and ixazomib. This combination aims to enhance the immune response while disrupting cancer cell growth, potentially improving patient outcomes. Additionally, the switch to oral ixazomib after initial cycles could offer more convenience and flexibility compared to treatments requiring frequent hospital visits.

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

Research has shown that a combination of three drugs—daratumumab, bortezomib, and dexamethasone—can effectively treat multiple myeloma, a type of blood cancer. Studies have found that this combination helps by slowing the disease's progression. In this trial, participants will receive a regimen that includes daratumumab, bortezomib, dexamethasone, and ixazomib. Daratumumab boosts the immune system to fight cancer cells. Bortezomib and ixazomib block certain proteins that cancer cells need to grow. Dexamethasone helps kill or stop the growth of cancer cells. Together, these treatments show promise for controlling multiple myeloma, especially when other treatments have failed. ^{1 2 3 4 6}

Who Is on the Research Team?

Oren C Pasvolsky, MD

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with multiple myeloma that has returned or hasn't responded to treatment. Participants must have had 1-3 prior treatments and shown some response, be in fair health (ECOG 0-2), agree to use contraception, and have measurable disease. They can't join if they've had certain drugs like ixazomib before, are allergic to study drugs, plan on having a stem cell transplant soon, or have other serious medical conditions.

Inclusion Criteria

My condition improved after previous cancer treatment.

I have been diagnosed with multiple myeloma through a biopsy.

I have had 1 to 3 treatment plans for my multiple myeloma.

Exclusion Criteria

I have not had radiotherapy within the specified time before joining.

I haven't taken strong CYP3A inducers or St. John's wort in the last 14 days.

I recently finished my multiple myeloma treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Phase 1

Participants receive daratumumab, bortezomib, and dexamethasone for 3 cycles of 28 days each

12 weeks

Multiple visits per cycle for drug administration

Treatment Phase 2

Participants receive daratumumab, ixazomib, and dexamethasone starting from cycle 4, repeating every 28 days

Indefinite, until disease progression or unacceptable toxicity

Regular visits per cycle for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 24 months

Follow-up at 30 days post-treatment, then periodically

What Are the Treatments Tested in This Trial?

Interventions

• Bortezomib
• Daratumumab
• Dexamethasone
• Ixazomib

Trial Overview The trial tests daratumumab with bortezomib and dexamethasone followed by daratumumab with ixazomib and dexamethasone in relapsed/refractory multiple myeloma patients. It examines whether this combination helps control the cancer better than previous treatments.

How Is the Trial Designed?

Group I: Treatment (daratumumab, bortezomib, dexamethasone, ixazomib) Experimental Treatment 5 Interventions

Patients receive daratumumab IV over 3.5-6.5 hours on days 1, 8, and 15, bortezomib SC on days 1, 4, 8, and 11, and dexamethasone IV over 15 minutes on days 1, 8, and 15 and PO on days 2, 4, 5, 9, 11, 12, and 16. Treatment repeats every 28 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive daratumumab IV over 3.5 hours on days 1 and 15 of cycles 4-7 and day 1 of subsequent cycles, ixazomib PO on days 1, 8, and 15, and dexamethasone IV over 15 minutes or PO once weekly. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in United States as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Canada as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Approved in Japan as Velcade for:

• Multiple myeloma
• Mantle cell lymphoma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

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

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. 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 ...

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 multiple myeloma: in combination with bortezomib, lenalidomide, and dexamethasone for ...

4. emedicine.medscape.com emedicine.medscape.com/article/2006866-overview

Multiple Myeloma Treatment Protocols Daratumumab/lenalidomide/bortezomib/dexamethasone (Dara-RVD, Dara-VRD):. This is the most commonly used quadruplet induction regimen.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9508512/

Roadmap for new practitioners to navigate the multiple ... This review aims to help advanced practice providers navigate through the diagnosis, staging, treatment, and supportive care considerations in the MM space.

6. 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.