Ixazomib + Cyclophosphamide + Dexamethasone for Multiple Myeloma

No longer recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Mayo Clinic

Must not be taking: CYP3A4 inducers

Disqualifiers: MGUS, Smoldering myeloma, Uncontrolled infection, others

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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of drugs—cyclophosphamide (a chemotherapy drug), dexamethasone (a corticosteroid), and ixazomib citrate (a proteasome inhibitor)—to determine the optimal dose and understand side effects for treating multiple myeloma or light chain amyloidosis. These conditions involve cancerous cells in the blood or organs, and the study aims to stop these cells from growing or spreading. People who have not yet received treatment for either condition and are experiencing symptoms might be suitable candidates for this trial. Participants should have a confirmed diagnosis and be able to manage daily life with their condition.

As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to contribute to groundbreaking medical advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot take certain medications like strong CYP3A4 inducers (e.g., rifampin, carbamazepine) 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 the combination of ixazomib citrate, cyclophosphamide, and dexamethasone is under study for safety in treating multiple myeloma and light chain amyloidosis. Here's what studies have found about the safety of these drugs:

For ixazomib citrate, research indicates it is generally well-tolerated. One study found that some patients experienced side effects like diarrhea, but serious side effects were less common.

Cyclophosphamide has long been used to treat multiple myeloma. Previous studies found common side effects like low white blood cell counts, but these did not result in treatment-related deaths.

Dexamethasone can cause side effects, especially in high doses. However, reducing the dose does not seem to affect treatment success, suggesting side effects can be managed by adjusting the dose.

Overall, while each drug can cause side effects, they are generally manageable and rarely lead to severe problems. This ongoing study explores how these drugs work together and aims to determine the best doses to minimize side effects while effectively treating the disease. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of ixazomib citrate, cyclophosphamide, and dexamethasone for treating multiple myeloma because it offers a unique approach compared to current treatments like lenalidomide, bortezomib, and melphalan. Unlike these standard options, ixazomib citrate is an oral proteasome inhibitor, making it more convenient for patients as it doesn't require injections or infusions. Additionally, this combination targets multiple pathways involved in cancer cell growth, potentially enhancing treatment effectiveness and overcoming resistance that can develop with single-agent therapies. This multi-faceted approach not only aims to improve patient outcomes but also maximizes convenience and flexibility in treatment.

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

This trial will evaluate the combination of ixazomib citrate, cyclophosphamide, and dexamethasone for treating multiple myeloma. Studies have shown that this combination can be effective, with research indicating that patients taking ixazomib as part of their treatment can experience over 20 months without disease progression. Ixazomib blocks certain proteins that cancer cells need to grow, helping to prevent the disease from spreading. Cyclophosphamide and dexamethasone are chemotherapy drugs that kill cancer cells or stop them from multiplying. Together, these drugs may offer a strong treatment option for those with multiple myeloma or light chain amyloidosis. ^{6 7 8 9 10}

Who Is on the Research Team?

Shaji K. Kumar, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for adults with untreated symptomatic multiple myeloma or light chain amyloidosis. Participants must have certain levels of monoclonal protein, adequate organ function, and agree to use effective contraception. Exclusions include recent major surgery, other serious illnesses, prior treatments for the conditions outside protocol guidelines, known allergies to study drugs, uncontrolled diseases like heart disease or infections.

Inclusion Criteria

Willing to return to return to enrolling institution for follow-up (during the active monitoring phase of the study)

You have a high level of a specific type of protein in your blood.

Agree to practice effective barrier contraception during the entire study treatment period and through 90 days after the last dose of study drug, OR

Exclusion Criteria

Participation in clinical trials with other investigational agents not included in this trial, =< 30 days prior to registration

I am not on any experimental treatments, but I may be taking bisphosphonates for bone health.

You have a known hepatitis B infection or an active hepatitis C infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Patients receive ixazomib citrate, cyclophosphamide, and dexamethasone. Treatment repeats every 28 days for up to 12 courses.

48 weeks

Monthly visits

Maintenance Therapy

Patients receive ixazomib citrate. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Until disease progression

Monthly visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

Every 3-6 months for 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Cyclophosphamide
• Dexamethasone
• Ixazomib Citrate

Trial Overview The trial tests a combination of Ixazomib Citrate with Cyclophosphamide and Dexamethasone in patients who haven't been treated before for their condition. It's designed to find out the best dose of Cyclophosphamide and how these drugs work together against cancer cells by stopping their growth.

How Is the Trial Designed?

Group I: Treatment (ixazomib citrate, cyclophosphamide, dexamethasone) Experimental Treatment 7 Interventions

INDUCTION THERAPY: Patients receive ixazomib citrate PO on days 1, 8, and 15 and cyclophosphamide PO and dexamethasone PO on days 1, 8, 15, and 22. Treatment repeats every 28 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. MAINTENANCE THERAPY: Patients receive ixazomib citrate PO on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

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

Approved in United States as Cytoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in European Union as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Canada as Neosar for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma
• Rheumatoid arthritis

Approved in Japan as Endoxan for:

• Breast cancer
• Ovarian cancer
• Multiple myeloma
• Leukemia
• Lymphoma

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Ixazomib, an oral proteasome inhibitor, significantly prolongs progression-free survival (PFS) in patients with relapsed and/or refractory multiple myeloma compared to placebo, as demonstrated in the TOURMALINE-MM1 trial involving adults who had received one to three prior therapies.

The treatment showed a favorable safety profile and resulted in a higher overall response rate, making ixazomib a valuable new option for patients with multiple myeloma who have undergone previous therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixazomib: A Review in Relapsed and/or Refractory Multiple Myeloma. Al-Salama, ZT., Garnock-Jones, KP., Scott, LJ.[2018]

In a study involving 43 East Asian patients with relapsed/refractory multiple myeloma, the oral proteasome inhibitor ixazomib was found to be rapidly absorbed and had a recommended phase 2/3 dose of 4.0 mg, with no dose-limiting toxicities reported.

The combination of ixazomib with lenalidomide and dexamethasone showed promising efficacy, with 65% of response-evaluable patients achieving at least a partial response, indicating that this treatment regimen is both active and well tolerated.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of ixazomib plus lenalidomide-dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study. Gupta, N., Goh, YT., Min, CK., et al.[2019]

In a phase 1/2 trial involving 65 patients with newly diagnosed multiple myeloma, the combination of oral ixazomib, lenalidomide, and dexamethasone was found to be generally well tolerated, with a maximum tolerated dose of ixazomib established at 2.97 mg/m².

The treatment resulted in a very good partial response or better in 58% of patients, indicating significant efficacy and supporting further phase 3 trials for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of ixazomib, an oral proteasome inhibitor, in combination with lenalidomide and dexamethasone in patients with previously untreated multiple myeloma: an open-label phase 1/2 study. Kumar, SK., Berdeja, JG., Niesvizky, R., et al.[2019]

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. ninlaro.com ninlaro.com/clinical-studies

Results with NINLARO® (ixazomib) In the clinical study, people taking the NINLARO treatment combination went more than a year and a half (20.6 months) without their multiple myeloma getting ...

2. ninlarohcp.com ninlarohcp.com/real-world-evidence

Real-World Evidence for the NINLARO® (ixazomib) Regimen Real-world and clinical trial data in relapsed/refractory multiple myeloma (RRMM): Evaluating treatment duration and comparing effectiveness and efficacy.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4189713/

An evidence-based review of ixazomib citrate and its ... With a median follow-up of 7 months, overall survival (OS) at 6 months was 96%. After these Phase I and II studies showed activity of the single-agent ixazomib ...

4. myeloma.org myeloma.org/ninlaro-ixazomib

Ninlaro (ixazomib) The FDA stated that it is not recommended in the maintenance setting or in newly diagnosed myeloma in combination with Rd outside of controlled clinical trials.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8205687/

A comparison of the efficacy and safety of ixazomib ... Conclusion: Compared with the combination of lenalidomide and DXMS, ixazomib combined with DXMS can achieve higher complete remission rate and more improved PFS ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11647735/

Rapid high‐dose cyclophosphamide as bridging treatment for ... The overall response rate was 80% and the clinical benefit rate was 100% in a heavily pretreated high‐risk cohort. Cytopenias were common but no deaths occurred ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8432336/

Safety and Efficacy of Doxorubicin, Cyclophosphamide ... There were no treatment-emergent deaths. The most common grade 3 to 4 adverse events were neutropenia (60%), infections (43%), thrombocytopenia (26%) and anemia ...

8. myeloma.org myeloma.org/cyclophosphamide

Cytoxan (Cyclophosphamide) | Int'l Myeloma Foundation Cytoxan (cyclophosphamide) is a chemotherapy medication used to treat multiple myeloma. Learn how this drug is used and its possible side effects.

9. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265022017499

Original Study Hyperfractionated Cyclophosphamide and ... Grade 3/4 hematologic toxicities were common, thrombocytopenia being the most frequent at 76%. Notably, 29-41% of patients per treatment group had existing ...

10. frontiersin.org frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1185991/full

Continuous low-dose cyclophosphamide plus prednisone ... Conclusion: This study demonstrates the metronomic chemotherapy regimen of CP is effective to RRMM patients with severe complications.