Narazaciclib + Dexamethasone for Multiple Myeloma

Overseen By Adriana Rossi, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Adriana Rossi

Must be taking: Dexamethasone

Must not be taking: CYP2C8, CYP3A4

Disqualifiers: Active infections, Cardiac conditions, others

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

Compensation: Varies

Number of Visits: 28

Duration: Up to 2 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment combination for people with multiple myeloma, a type of blood cancer affecting plasma cells. Researchers are evaluating the safety and effectiveness of combining narazaciclib, a new drug targeting cancer cell growth, with dexamethasone, a commonly used steroid. The study seeks participants whose multiple myeloma has worsened despite trying at least two other treatments, including a proteasome inhibitor, an immunomodulatory drug, and a CD38-targeting antibody. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, it mentions that you should not be taking strong inducers or inhibitors of certain liver enzymes (CYP2C8 and CYP3A4) and that all previous cancer therapies should be stopped at least 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 narazaciclib and dexamethasone is still under study to ensure safety for people. Narazaciclib is a new drug targeting specific proteins in cancer cells. Early studies with patients have demonstrated that this combination can be tolerated, but researchers continue to explore its full safety profile.

As the trial progresses, researchers are closely monitoring the treatment's safety. They aim to determine the optimal dose that patients can tolerate without serious side effects. While the treatment appears promising, understanding its safety remains a priority.

Dexamethasone is already a well-known drug used in many treatments, with established safety. The main focus is on how effectively narazaciclib works with it in treating multiple myeloma. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for multiple myeloma?

Most treatments for multiple myeloma typically involve therapies like proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies. But Narazaciclib works differently by targeting specific enzymes that are crucial for cancer cell growth, offering a new mechanism of action. Researchers are excited about Narazaciclib because it has the potential to enhance the effectiveness of existing treatments when combined with dexamethasone. This combination aims to provide a more robust response in patients, potentially improving outcomes for those who haven't responded well to current therapies.

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

This trial will evaluate the combination of Narazaciclib and dexamethasone for treating multiple myeloma. Studies have shown that Narazaciclib, when combined with dexamethasone, may help treat this condition. Research suggests that Narazaciclib blocks certain proteins that cancer cells need to grow. In lab and animal studies, this combination effectively stopped cancer cell growth. Although more research is needed to confirm these results in humans, early signs are promising. Dexamethasone, already a standard treatment, reduces inflammation and kills cancer cells. Together, these drugs might offer a new way to combat this challenging cancer. ^{1 2 3 6 7}

Who Is on the Research Team?

Adriana Rossi, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Samir Parekh, MBBS

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for people with multiple myeloma, a type of blood cancer, who have tried other treatments that didn't work or stopped working. Participants should be able to take oral medication and handle steroid treatment.

Inclusion Criteria

Able to provide a signed Written Informed Consent before any study-related procedure

I am able to care for myself but may not be able to do heavy physical work.

I last received BCMA-targeted therapy, like CAR-T, over 60 days ago.

Exclusion Criteria

I agree to use two effective birth control methods if I can have children.

I have had a stem cell transplant or other cell therapy within the last 2 months.

I do not have specific blood disorders or brain involvement.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ON 123300 (NARAZACICLIB) and dexamethasone in 28-day cycles, continuing as long as the drug shows anti-myeloma activity and the patient does not exhibit any dose-limiting toxicities.

Up to 2 years

Per Cycle/Every 28 Days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Narazaciclib

Trial Overview Researchers are testing ON 123300 (Narazaciclib), a new pill that targets specific proteins in cancer cells, combined with dexamethasone, a steroid. They want to see if this combo is safe and helps control the disease better than current options.

How Is the Trial Designed?

Group I: ON 123300 (NARAZACICLIB) + dexamethasone Experimental Treatment 2 Interventions

Participants will continue 28-day cycles of ON 123300 (NARAZACICLIB) + dexamethasone as long as the drug shows anti-myeloma activity with a disease response ≥PR (PR, VGPR, CR) and the patient does not exhibit any DLTs and the study is open. Patients will continue the regimen until disease progression/intolerable toxicity/death, withdrawal OR for a maximum up to 2 years after enrollment.

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?

Adriana Rossi

Lead Sponsor

Trials

1

Recruited

40+

Published Research Related to This Trial

The combination of ixazomib, cyclophosphamide, and dexamethasone (ICd) followed by ixazomib maintenance showed a 33% complete response (CR) and very good partial response (VGPR) rate in elderly patients with newly diagnosed multiple myeloma, indicating its efficacy as a treatment option.

The treatment was generally well-tolerated, with 73% of patients experiencing grade ≥3 adverse events, but only 3% discontinued maintenance due to adverse effects, suggesting a manageable safety profile for this regimen.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

All-oral ixazomib, cyclophosphamide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma. Dimopoulos, MA., Grosicki, S., Jędrzejczak, WW., et al.[2020]

In a phase 3 trial involving 402 patients with previously treated multiple myeloma, the combination of selinexor, bortezomib, and dexamethasone resulted in a median progression-free survival of 13.93 months, significantly longer than the 9.46 months observed with standard bortezomib and dexamethasone (p=0.0075).

The selinexor combination therapy was associated with lower rates of peripheral neuropathy (21%) compared to the standard treatment (34%), suggesting a safer profile regarding this common side effect.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Grosicki, S., Simonova, M., Spicka, I., et al.[2022]

Dexamethasone remains a crucial part of multiple myeloma treatment, enhancing the effectiveness of novel therapies and improving response rates across all treatment phases.

New formulations of dexamethasone aim to reduce the number of pills patients need to take, which could help improve adherence to treatment and minimize medication errors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From mechanism to resistance - changes in the use of dexamethasone in the treatment of multiple myeloma. Rosenberg, AS.[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 study of 80 newly diagnosed multiple myeloma patients, ixazomib combined with dexamethasone showed a higher complete remission rate compared to lenalidomide with dexamethasone, indicating it may be a more effective treatment option.

Both treatment combinations resulted in similar progression-free survival and overall survival rates, but ixazomib was associated with a higher incidence of mild peripheral neuropathy, suggesting it is generally safe but may have some side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A comparison of the efficacy and safety of ixazomib and lenalidomide combined with dexamethasone in the treatment of multiple myeloma. Zheng, Z., Lin, K.[2021]

In a study of 16 patients with relapsed or refractory multiple myeloma, the combination of bortezomib and dexamethasone resulted in a high clinical response rate of 87.5%, with 6 patients achieving near complete response.

The treatment was associated with manageable side effects, primarily gastrointestinal issues and thrombocytopenia, which were alleviated with supportive care, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bortezomib in combination with dexamethasone for the treatment of relapsed or refractory multiple myeloma]. Yuan, ZG., Hou, J., Zhou, F., et al.[2015]

In two phase 2 studies involving 256 patients with relapsed or refractory multiple myeloma, adding dexamethasone to bortezomib improved treatment responses, with 18% of patients in the SUMMIT study and 33% in the CREST study showing better outcomes.

The combination therapy did not significantly increase the type or number of adverse events, indicating that dexamethasone can enhance efficacy without adding prohibitive toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bortezomib in combination with dexamethasone for the treatment of patients with relapsed and/or refractory multiple myeloma with less than optimal response to bortezomib alone. Jagannath, S., Richardson, PG., Barlogie, B., et al.[2022]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06351644?term=AREA%5BBasicSearch%5D(NARAZACICLIB)&rank=1

ON 123300 (Narazaciclib) and Dexamethasone in Patients ... In this study, the researchers will test the safety and preliminary efficacy of inhibition of CDK4 and ARK5 by ON 123300 ( NARAZACICLIB ) in combination with ...

2. mountsinai.org mountsinai.org/clinical-trials/on-123300-narazaciclib-dexamethasone-in-patients-with-relapsed-refractory-multiple-myeloma

ON 123300 (Narazaciclib) and Dexamethasone in Patients ... ON 123300 (Narazaciclib) and Dexamethasone in Patients With Relapsed and/or Refractory Multiple Myeloma. ID#: NCT06351644. Age: 18 years - 66+. Gender: All.

3. trialx.com trialx.com/clinical-trials/listings/317007/on-123300-narazaciclib-and-dexamethasone-in-patients-with-relapsed-andor-refractory-multiple-myeloma/

ON 123300 (Narazaciclib) and Dexamethasone in Patients ... In this study, the researchers will test the safety and preliminary efficacy of inhibition of CDK4 and ARK5 by ON 123300 (NARAZACICLIB) in ...

4. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-05647

Narazaciclib and Dexamethasone for the Treatment of ... Narazaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Dexamethasone is in a class of medications called ...

5. withpower.com withpower.com/trial/phase-2-relapsed-or-refractory-multiple-myeloma-5-2024-4899d

Narazaciclib + Dexamethasone for Multiple Myeloma Participants receive ON 123300 (NARAZACICLIB) and dexamethasone in 28-day cycles, continuing as long as the drug shows anti-myeloma activity and the patient ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06351644/on-123300-narazaciclib-and-dexamethasone-in-patients-with-relapsed-and-or-refractory-multiple-myeloma

ON 123300 (Narazaciclib) and Dexamethasone in Patients ... In this study, the researchers will test the safety and preliminary efficacy of inhibition of CDK4 and ARK5 by ON 123300 (NARAZACICLIB) in ...

7. clin.larvol.com clin.larvol.com/trial-detail/NCT06351644

ON 123300 (Narazaciclib) and Dexamethasone in Patients ... Phase I: Determination of the optimal biological dose (OBD) of the combination of ON 123300 (NARAZACICLIB) and dexamethasone in relapsed MM patients - defined ...