Ixazomib + Pomalidomide + Dexamethasone for Multiple Myeloma

Overseen By Emily Benjamin

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Paul Richardson, MD

Must be taking: ImiDs, Proteasome inhibitors

Must not be taking: CYP3A inducers, CYP1A2 inhibitors

Disqualifiers: Other malignancy, Cardiovascular conditions, GI disease, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of three drugs—ixazomib (a proteasome inhibitor), pomalidomide (an immunomodulatory drug), and dexamethasone (a corticosteroid)—to evaluate their combined effectiveness in treating multiple myeloma, a type of blood cancer that has returned or not responded to previous treatments. The trial aims to determine the optimal dose and assess the combination's effectiveness in managing the condition. Participants should have had multiple myeloma previously and require treatment again after past therapies failed. As a Phase 1, Phase 2 trial, this research seeks to understand the treatment's mechanism and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to advancements in multiple myeloma treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that you cannot have certain treatments like strong CYP3A inducers or inhibitors within 14 days before starting the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research has shown that the combination of ixazomib, pomalidomide, and dexamethasone can be safe for people with relapsed or refractory multiple myeloma. One study found that this combination helped patients live longer without their disease worsening, particularly for those who did not respond to a similar drug, lenalidomide. The side effects, or unwanted reactions to the treatment, were manageable.

Another study found that patients tolerated the treatment fairly well. Although some side effects occurred, they were generally expected and could be managed with extra care or by adjusting the dose. While more research is needed, early findings suggest that this treatment can be safely used under medical supervision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Ixazomib, Pomalidomide, and Dexamethasone for treating multiple myeloma because it offers a fresh approach compared to existing therapies. Most treatments for multiple myeloma target the cancer cells directly, but this combo works synergistically to enhance the immune response and inhibit cancer cell growth more effectively. Ixazomib, in particular, is a proteasome inhibitor that disrupts protein breakdown in cancer cells, leading to their death, while Pomalidomide modulates the immune system to attack cancer more vigorously. This combination could potentially offer more effective management of multiple myeloma with possibly fewer side effects, making it a promising option for patients.

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

Research has shown that the combination of ixazomib, pomalidomide, and dexamethasone holds promise for treating relapsed or refractory multiple myeloma (RRMM). In this trial, participants will receive this combination treatment. Studies have found that adding ixazomib to pomalidomide and dexamethasone extends the time patients live without their disease worsening. Patients whose multiple myeloma did not respond to other treatments have demonstrated positive results with this drug combination. This treatment has also proven effective for those who did not respond to lenalidomide, a common therapy for multiple myeloma. These findings offer hope for people with hard-to-treat multiple myeloma. ^{1 2 4 6 7}

Who Is on the Research Team?

Omar Nadeem, MD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for adults with Multiple Myeloma that has come back or didn't respond to treatment. They must have tried at least two therapies, be in decent physical shape (able to perform daily activities), and not have had certain other treatments recently. Women who can get pregnant must follow specific pregnancy testing rules.

Inclusion Criteria

I've had at least two treatments for my condition or one if it included specific drugs and my disease got worse within 60 days after treatment.

Registered into the mandatory POMALYST REMS® program and willing and able to comply with its requirements

I agree to follow the pregnancy testing schedule as required.

Exclusion Criteria

I do not have any health or personal issues that would make it hard for me to follow the study's requirements.

I have a GI condition or had surgery that may affect medication absorption.

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

Phase I Treatment

Phase I will follow a standard '3 +3' dose escalation design to test the safety of ixazomib with pomalidomide and dexamethasone

21 days per cycle

3-6 patients per dose level

Phase II Treatment

Single-arm open-label enrollment with dosing based on the MTD determination in Phase I

21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

up to 60 months

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Ixazomib
• Pomalidomide

Trial Overview The study tests a combination of three drugs: Ixazomib, Pomalidomide, and Dexamethasone given twice weekly for patients whose Multiple Myeloma has relapsed or is refractory. It's designed to see how safe this mix is and how well it works.

How Is the Trial Designed?

Group I: ixazomib plus pomalidomide and dexamethasone Experimental Treatment 3 Interventions

The study drugs will be administered within a 21-day cycle * Phase I will follow a standard "3 +3" dose escalation design: Starting with the first cohort, 3 to 6 patients will be treated at this and each subsequent dose level. * The Phase II portion of the study will be a single-arm open-label enrollment with dosing based on the MTD determination in the Phase I portion of the study

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

Approved in European Union as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases
• Immune system disorders

Approved in United States as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders
• Neoplastic diseases
• Nervous system disorders

Approved in Canada as Dexamethasone for:

• Inflammation
• Allergic reactions
• Respiratory diseases
• Skin conditions
• Eye diseases

Approved in Japan as Dexamethasone for:

• Inflammatory conditions
• Allergic states
• Respiratory diseases
• Blood disorders

Who Is Running the Clinical Trial?

Paul Richardson, MD

Lead Sponsor

Trials

2

Recruited

780+

Paul G. Richardson, MD

Lead Sponsor

Trials

2

Recruited

780+

Omar Nadeem, MD

Lead Sponsor

Trials

3

Recruited

160+

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

Published Research Related to This Trial

Pomalidomide, combined with low-dose dexamethasone, has been shown to be effective in treating adult patients with relapsed and refractory multiple myeloma, significantly improving progression-free survival and overall response rates compared to high-dose dexamethasone.

The treatment demonstrated a manageable safety profile and was effective across various patient subgroups, including those who were refractory to previous therapies, indicating its potential as a valuable salvage therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: a review of its use in patients with recurrent multiple myeloma. Scott, LJ.[2022]

Pomalidomide, when combined with low-dose dexamethasone, significantly improves progression-free survival and overall survival in adults with relapsed and refractory multiple myeloma, based on results from multinational phase II and III studies involving patients who had undergone at least two prior treatments.

The treatment has a manageable safety profile, with the most common serious side effects being neutropenia, infections, anemia, and thrombocytopenia, making it a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. Hoy, SM.[2018]

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 3 trial involving 455 patients with refractory or relapsed multiple myeloma, pomalidomide combined with low-dose dexamethasone significantly improved progression-free survival and overall survival compared to high-dose dexamethasone.

The treatment was effective across all patient subgroups, regardless of their previous treatments, and showed no cross-resistance with prior therapies, making it a strong candidate for standard care in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of prior treatment and depth of response on survival in MM-003, a randomized phase 3 study comparing pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone in relapsed/refractory multiple myeloma. San Miguel, JF., Weisel, KC., Song, KW., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02119468

Ixazomib Plus Pomalidomide and Dexamethasone in ... Giving ixazomib with pomalidomide and dexamethasone may be an effective treatment for relapsed or relapsed/refractory multiple myeloma. Detailed Description.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39058954/

ixazomib, pomalidomide, and dexamethasone for patients ... A randomized phase 2 study to evaluate the efficacy and safety of combining the oral proteasome inhibitor ixazomib (IXA) with pomalidomide (POM) and ...

3. ashpublications.org ashpublications.org/bloodadvances/article/8/19/5039/517176/Alliance-A061202-ixazomib-pomalidomide-and

ixazomib, pomalidomide, and dexamethasone for patients ... IXA added to POM and DEX improved PFS in patients with LEN-refractory multiple myeloma at first relapse.

4. haematologica.org haematologica.org/article/view/11819

Ixazomib, pomalidomide and dexamethasone in relapsed ... These data confirm that we have recruited patients that were truly high-risk being lenalidomide refractory RRMM, even in early relapse L2 and L3 ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2950328025000020

Clarithromycin, ixazomib, pomalidomide, dexamethasone ... After the first 6 patients were enrolled, the protocol was amended to continue at dose level 1 given an acceptable toxicity profile and early efficacy data.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8713771/

A phase I/II study of ixazomib, pomalidomide, and ... Here we present the safety and long-term efficacy results from the 24 patients enrolled onto the phase I study and the 5 evaluable patients randomized to IXA- ...

7. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/2014/502971/A-Phase-II-Multicenter-Clinical-Trial-Assessing

A Phase II Multicenter Clinical Trial Assessing the Safety and ... We report the outcomes of the IPoD-790 clinical trial (NCT04790474), an all-oral regimen: ixazomib (IXA), pomalidomide (POM) and dexamethasone (DEX) (IPd) ...