Ixazomib for Kaposi Sarcoma

Recruiting at 9 trial locations

Overseen By Erin Reid, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AIDS Malignancy Consortium

Must be taking: Antiretrovirals

Must not be taking: CYP3A inducers

Disqualifiers: Uncontrolled illness, Hepatitis B, 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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 48 weeks

41 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies how well ixazomib works in treating patients with Kaposi sarcoma. Ixazomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop all current medications, but you must stop taking any strong CYP3A inducers (like rifampin or St. John's wort) at least 14 days before starting the trial. If you are on antiretroviral therapy for HIV, you must be on a stable regimen for at least 4 weeks and avoid certain medications that reduce ixazomib exposure.

Is Ixazomib safe for humans?

There is no specific safety data available for Ixazomib in the context of Kaposi Sarcoma, but it has been studied for other conditions. Generally, Ixazomib (also known as Ninlaro or MLN9708) is used in treating multiple myeloma and has been found to be safe for human use, with common side effects including nausea, diarrhea, and low blood counts. ^{1 2 3 4 5}

How is the drug Ixazomib unique for treating Kaposi Sarcoma?

Ixazomib is unique because it is an oral proteasome inhibitor, which means it works by blocking a protein complex that breaks down unneeded proteins in cells, potentially leading to cancer cell death. This mechanism is different from traditional chemotherapy and offers a convenient oral administration compared to other treatments that may require injections or infusions. ^{6 7 8 9 10}

Research Team

Erin Reid, MD

Principal Investigator

AIDS Malignancy Consortium

Eligibility Criteria

Adults with Kaposi sarcoma, good performance status (able to carry out daily activities), and adequate organ function can join. They must have measurable skin lesions, not be pregnant or breastfeeding, use contraception if of childbearing potential, and have a life expectancy over 3 months. HIV-positive patients need stable antiretroviral therapy for at least 4 weeks.

Inclusion Criteria

I can do most of my daily activities but might need help.

My platelet count is at least 75,000 without recent transfusions.

My kidney function, measured by creatinine levels, is normal or my creatinine clearance is at least 30 mL/min.

Exclusion Criteria

I haven't taken proteasome inhibitors for Kaposi sarcoma in the last 2 years, nor have I ever taken ixazomib.

I have a stomach or intestine condition that affects how I absorb pills or makes it hard for me to swallow.

I am not taking any strong medication that affects liver enzymes or St. John's wort.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ixazomib orally on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 cycles.

48 weeks

3 visits per cycle (in-person)

Extended Treatment

Participants with complete or partial response may continue treatment for an additional 12 cycles.

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment completion.

4 weeks, then periodically for up to 2 years

Treatment Details

Interventions

• Ixazomib Citrate

Trial Overview The trial is testing Ixazomib's effectiveness on Kaposi sarcoma by seeing if it can stop tumor growth. It involves taking the drug orally and monitoring its impact through health questionnaires and assessments.

Participant Groups

Group I: Treatment (ixazomib) Experimental Treatment 3 Interventions

Patients receive ixazomib PO on days 1, 8, and 15. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with complete or partial response may continue treatment for an additional 12 cycles in the absence of disease progression or unacceptable toxicity.

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

Approved in European Union as Ninlaro for:

• Multiple myeloma

Approved in United States as Ninlaro for:

• Multiple myeloma

Approved in Canada as Ninlaro for:

• Multiple myeloma

Approved in Japan as Ninlaro for:

• Multiple myeloma

Who Is Running the Clinical Trial?

AIDS Malignancy Consortium

Lead Sponsor

Trials

64

Recruited

9,600+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

The introduction of highly active antiretroviral therapy (HAART) has significantly decreased the prevalence and mortality rates of AIDS-related Kaposi's sarcoma, improving patient outcomes compared to the pre-HAART era.

Advancements in understanding the disease's molecular mechanisms have opened up new potential therapeutic strategies, alongside the effective use of conventional chemotherapy and immunomodulatory treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of AIDS-related Kaposi's sarcoma. Di Lorenzo, G., Konstantinopoulos, PA., Pantanowitz, L., et al.[2022]

In a study of 12 patients with Kaposi's sarcoma (KS) treated with biologic or small molecule drugs, nine patients experienced KS onset or reactivation after a median of 6 months, particularly with drugs like rituximab and infliximab.

Despite the initial worsening of KS in some patients, all cases achieved a complete response after stopping the problematic drugs, indicating that careful monitoring and management of treatment are crucial for KS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Kaposi's sarcoma, biologics and small molecules: Navigating the complex interplay between host immunity and viral biology. A case series with focused review of the literature. Brambilla, L., Maronese, CA., Zelin, E., et al.[2022]

In a study involving 18 male patients with progressive classical Kaposi sarcoma, the combination of nivolumab and ipilimumab showed a high overall response rate of 87%, indicating significant efficacy in this challenging condition.

The treatment resulted in a 6-month progression-free survival rate of 76.5%, with only 22% of patients experiencing severe adverse events, suggesting a favorable safety profile for this combination therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated classical Kaposi sarcoma (cKS). Zer, A., Icht, O., Yosef, L., et al.[2022]

In a review of 320 patients treated with immunotherapy, 9 men with HIV-associated Kaposi sarcoma (KS) showed a significant response, with 67% achieving partial or complete remission after treatment with nivolumab or pembrolizumab.

The treatment was well-tolerated, with no severe drug-related toxicities reported, and some patients even experienced an increase in CD4 counts, suggesting potential immune system benefits alongside tumor reduction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful Treatment of HIV-Associated Kaposi Sarcoma with Immune Checkpoint Blockade. Galanina, N., Goodman, AM., Cohen, PR., et al.[2021]

Liposomal anthracyclines and paclitaxel have been identified as highly effective chemotherapy options for treating Kaposi's sarcoma (KS), showcasing significant progress in therapy for this disease.

New experimental agents, including antiangiogenesis drugs like TNP-470 and thalidomide, as well as oral 9-cis retinoic acid, are showing promise in early studies, indicating a potential for innovative treatments targeting the underlying causes of KS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy for Kaposi's sarcoma: recent advances and experimental approaches. Yarchoan, R.[2020]

Ixazomib is an orally taken proteasome inhibitor that works by blocking the β5 subunit of the proteasome, and it was approved by the FDA in 2015 for treating multiple myeloma in combination with lenalidomide and dexamethasone after at least one prior therapy.

Currently, ixazomib is being studied in Phase III trials for newly diagnosed multiple myeloma and other conditions, indicating its potential for broader applications in treating various cancers and autoimmune diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ixazomib: First Global Approval. Shirley, M.[2018]

Ixazomib, an oral proteasome inhibitor, has been shown to significantly improve progression-free survival in patients with relapsed and/or refractory multiple myeloma when combined with lenalidomide and dexamethasone, with a median survival of 20.6 months compared to 14.7 months for the placebo group.

The drug works by selectively inhibiting the 20S proteasome, leading to the accumulation of proteins that induce stress and apoptosis in myeloma cells, making it a promising treatment option for patients who have undergone prior therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological characteristics and clinical study results of the oral proteasome inhibitor ixazomib (NINLARO® capsules; 2.3 mg, 3 mg, and 4 mg)]. Machida, M., Fukunaga, S., Hara, T.[2019]

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]

Ixazomib is the first oral proteasome inhibitor being tested for multiple myeloma, showing promising antitumor activity in preclinical studies and manageable side effects in early clinical trials.

Preliminary results indicate that ixazomib is effective both as a standalone treatment for relapsed/refractory multiple myeloma and in combination with other drugs for newly diagnosed patients, with ongoing Phase III studies to further evaluate its efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The investigational proteasome inhibitor ixazomib for the treatment of multiple myeloma. Richardson, PG., Moreau, P., Laubach, JP., et al.[2015]

In a phase 3 trial involving 722 patients with relapsed or refractory multiple myeloma, the addition of ixazomib to lenalidomide and dexamethasone significantly improved progression-free survival, with a median of 20.6 months compared to 14.7 months for the placebo group.

The safety profile of ixazomib was comparable to placebo, with similar rates of serious adverse events and overall survival, although some specific side effects like thrombocytopenia and rash were more common in the ixazomib group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. Moreau, P., Masszi, T., Grzasko, N., et al.[2022]

References

1. England pubmed.ncbi.nlm.nih.gov

Management of AIDS-related Kaposi's sarcoma. [2022]

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

Kaposi's sarcoma, biologics and small molecules: Navigating the complex interplay between host immunity and viral biology. A case series with focused review of the literature. [2022]

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

Phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated classical Kaposi sarcoma (cKS). [2022]

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

Successful Treatment of HIV-Associated Kaposi Sarcoma with Immune Checkpoint Blockade. [2021]

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

Therapy for Kaposi's sarcoma: recent advances and experimental approaches. [2020]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Ixazomib: First Global Approval. [2018]

7. Japan pubmed.ncbi.nlm.nih.gov

[Pharmacological characteristics and clinical study results of the oral proteasome inhibitor ixazomib (NINLARO® capsules; 2.3 mg, 3 mg, and 4 mg)]. [2019]

8. France pubmed.ncbi.nlm.nih.gov

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

9. England pubmed.ncbi.nlm.nih.gov

The investigational proteasome inhibitor ixazomib for the treatment of multiple myeloma. [2015]

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

Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. [2022]