Ixazomib + Cyclophosphamide + Dexamethasone for Multiple Myeloma

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

87 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This phase I/II trial studies the side effects and the best dose of cyclophosphamide when given together with ixazomib citrate and dexamethasone in treating patients with previously untreated symptomatic multiple myeloma or light chain amyloidosis. Drugs used in chemotherapy, such as cyclophosphamide and dexamethasone, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Ixazomib citrate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving cyclophosphamide together with ixazomib citrate and dexamethasone may be a better treatment for multiple myeloma or light chain amyloidosis.

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 the combination of Ixazomib, Cyclophosphamide, and Dexamethasone safe for humans?

The combination of Ixazomib, Cyclophosphamide, and Dexamethasone has been studied in patients with multiple myeloma and is generally well tolerated. Common side effects include low blood cell counts, tiredness, and stomach issues. The treatment is considered safe, with manageable side effects, for people with multiple myeloma. ^{1 2 3 4 5}

What makes the drug combination of Ixazomib, Cyclophosphamide, and Dexamethasone unique for treating multiple myeloma?

This drug combination is unique because it includes ixazomib, the first oral proteasome inhibitor, making it a convenient all-oral regimen. It is effective and well-tolerated in newly diagnosed multiple myeloma patients, offering a novel option compared to traditional intravenous treatments. ^{1 6 7 8 9}

What data supports the effectiveness of the drug combination Ixazomib, Cyclophosphamide, and Dexamethasone for treating multiple myeloma?

In a study involving patients with newly diagnosed multiple myeloma, the combination of Ixazomib, Cyclophosphamide, and Dexamethasone showed a partial response in 77% of patients, with 35% achieving a very good partial response or better. This suggests that the drug combination is effective in treating multiple myeloma. ^{1 4 5 6 9}

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

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 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]

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 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]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Comparison between ixazomib+cyclophosphamide+dexamethasone regimen and ixazomib+dexamethasone regimen for elderly and frail patients having newly diagnosed multiple myeloma. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Phase 1/2 trial of ixazomib, cyclophosphamide and dexamethasone in patients with previously untreated symptomatic multiple myeloma. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and safety of ixazomib plus lenalidomide-dexamethasone in Asian patients with relapsed/refractory myeloma: a phase 1 study. [2019]

4. England 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. [2023]

5. France pubmed.ncbi.nlm.nih.gov

Ixazomib: A Review in Relapsed and/or Refractory Multiple Myeloma. [2018]

6. England pubmed.ncbi.nlm.nih.gov

Twice-weekly ixazomib in combination with lenalidomide-dexamethasone in patients with newly diagnosed multiple myeloma. [2019]

7. England pubmed.ncbi.nlm.nih.gov

European Medicines Agency review of ixazomib (Ninlaro) for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. [2023]

8. Czech Republic pubmed.ncbi.nlm.nih.gov

Ixazomib - lenalidomide - dexamethason in heavily pretreated multiple myeloma patients - case reports. [2023]

9. England 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. [2019]