Ixazomib for Kaposi Sarcoma
Recruiting in Palo Alto (17 mi)
+9 other locations
Overseen byRonald T Mitsuyasu
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: AIDS Malignancy Consortium
Must be taking: Antiretrovirals
Must not be taking: CYP3A inducers
Disqualifiers: Uncontrolled illness, Hepatitis B, others
No Placebo Group
Prior Safety Data
Approved in 4 Jurisdictions
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.
12345How 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.
678910Eligibility 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.
+14 more
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.
+12 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Treatment (ixazomib)Experimental Treatment3 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
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Miami Miller School of MedicineMiami, FL
Zuckerberg San Francisco General HospitalSan Francisco, CA
Abramson Cancer Center at Pennsylvania HospitalPhiladelphia, PA
Virginia Mason Medical CenterSeattle, WA
More Trial Locations
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Who Is Running the Clinical Trial?
AIDS Malignancy ConsortiumLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Management of AIDS-related Kaposi's sarcoma. [2022]The advent of highly active antiretroviral therapy (HAART) has lead to a substantial reduction in the prevalence, morbidity, and mortality associated with AIDS-related Kaposi's sarcoma. Similarly, concomitant advances in chemotherapy and supportive-care protocols have allowed for Kaposi's sarcoma to be managed more effectively in comparison with the pre-HAART era. Furthermore, developments in our understanding of the pathogenesis of Kaposi's sarcoma have identified several molecular targets that can potentially provide new therapeutic strategies. This Review discusses the role of conventional chemotherapeutic and immunomodulatory agents in the treatment of Kaposi's sarcoma and summarises the current status and future prospects of novel molecularly targeted agents in the treatment of this disease.
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]The consequences of cytokine-specific immune modulation in the development and course of Kaposi's sarcoma (KS) are poorly understood. A retrospective chart review of patients treated with biologic/small molecule drugs and followed at the dedicated KS outpatient service of our Dermatology Unit was performed. The literature on biologic and small molecule drug use in KS patients was also reviewed. Data concerning 12 KS patients treated with biologic/small molecule drugs were collected. After a median delay of 6 months following biologic or small molecule drug introduction, nine patients experienced either KS onset or reactivation. Drugs associated with KS onset or flaring were: rituximab, infliximab, ruxolitinib apremilast (1), mirikizumab, abatacept (1). After a median follow-up of 25 months, all cases achieved persistent complete response through culprit drug discontinuation or drug withdrawal plus treatment. No effect on KS course was recorded with tocilizumab and vedolizumab. Based on our experience with the largest case series reported to date as well as the available literature, tocilizumab and ustekinumab seem to exert an overall neutral effect on KS. On the other hand, rituximab, infliximab, and ruxolitinib have been associated with the development or worsening of pre-existing KS and should be carefully pondered before use. Due to limited and partly controversial evidence, no definitive conclusions can be drawn on vedolizumab, apremilast, mirikizumab, abatacept.
Phase II single-arm study of nivolumab and ipilimumab (Nivo/Ipi) in previously treated classical Kaposi sarcoma (cKS). [2022]Classical Kaposi sarcoma (cKS) is a rare human herpesvirus 8-associated sarcoma with limited treatment options. We evaluated the efficacy and safety of nivolumab in combination with ipilimumab in patients with previously treated progressive cKS.
Successful Treatment of HIV-Associated Kaposi Sarcoma with Immune Checkpoint Blockade. [2021]Kaposi sarcoma (KS) is an incurable, human immunodeficiency virus (HIV)-associated malignancy. We reviewed 320 immunotherapy-treated patient records. Seventeen had HIV-associated malignancies, including nine men with KS. Median viral load was 20 copies/mL (range, undetectable to 549,704) and median CD4 count was 256 cells/μL (range, 10-603). Eight patients received nivolumab and one received pembrolizumab. Six patients (67%) achieved partial (N = 5) or complete remission (N = 1). No drug-related grade >2 toxicities occurred. In seven patients, CD4 counts increased (P = 0.09). Tissue and/or blood-derived circulating tumor DNA (ctDNA) was evaluated by next-generation sequencing. Four evaluable patients each showed anomalies in distinct genes: TP53, KRAS, TLL2, PTPN6 (tissue and/or ctDNA), and NF1 (ctDNA). Tumor mutational burden was low, and PD-L1 immunohistochemistry was negative (three and four assessable patients, respectively). Responders included patients with low CD4 counts, high HIV load, and/or visceral disease. In summary, checkpoint blockade demonstrated significant antitumor activity and low toxicity in patients with HIV-associated KS. Cancer Immunol Res; 6(10); 1129-35. ©2018 AACR.
Therapy for Kaposi's sarcoma: recent advances and experimental approaches. [2020]The past several years have seen demonstrable progress in the therapy of Kaposi's sarcoma (KS). Liposomal anthracyclines and paclitaxel have been found to be highly effective chemotherapeutic agents for this disease. Recent advances in our understanding of the pathogenesis of KS have led to the consideration of various new experimental agents. Two antiangiogenesis agents, TNP-470 and thalidomide, have been determined to induce some responses in KS, and others are now in early clinical trials or in preclinical development. Oral 9-cis retinoic acid has been shown to have anti-KS activity, and preliminary studies suggest that a urinary protein found in preparations of human chorionic gonadotropin also has activity. Effective anti-HIV treatment has been shown to affect the growth of KS, and the discovery of a new herpesvirus as a causative agent for KS has offered new potential targets for attack.
Ixazomib: First Global Approval. [2018]Ixazomib (Ninlaro(®)) is an orally bioavailable, reversible proteasome inhibitor developed by Millennium Pharmaceuticals, Inc. (now Takeda Oncology). Ixazomib acts by binding to and inhibiting the β5 subunit of the 20S proteasome. In November 2015, the US FDA approved ixazomib for use in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Ixazomib is under regulatory review for this indication in the EU. Phase III development of ixazomib is underway worldwide for newly-diagnosed multiple myeloma (in patients who are not eligible for stem cell transplant, or as maintenance therapy) and for relapsed or refractory systemic light chain (AL) amyloidosis. Ixazomib is also under phase I-II development for the treatment of several other haematological and non-haematological malignancies, graft-versus-host disease and lupus nephritis. This article summarizes the milestones in the development of ixazomib leading to this first approval for multiple myeloma.
[Pharmacological characteristics and clinical study results of the oral proteasome inhibitor ixazomib (NINLARO® capsules; 2.3 mg, 3 mg, and 4 mg)]. [2019]Ixazomib (Ninlaro® capsule) is an oral small molecule 20S proteasome inhibitor created by Millennium Pharmaceuticals, Inc (Takeda Oncology Company). Ubiquitin proteasome system is a major regulatory system for maintaining protein homeostasis, and an important mechanism for degrading proteins, such as those involved in proliferation regulation, cell cycle regulation and apoptosis, in cells. Ixazomib selectively and reversibly binds to the β5 subunit of the 20S proteasome, inhibits its chymotrypsin-like activity, and thereby accumulates ubiquitinated proteins. It induces ER stress and apoptosis of myeloma cells. The phase 3, randomized, double-blind, multicenter global study (TOURMALINE-MM1) in patients with relapsed and/or refractory multiple myeloma, who have received 1 to 3 prior lines of therapy, showed that addition of ixazomib to lenalidomide-dexamethasone (ixazomib-Rd) demonstrated significant improvement in progression-free survival (hazard ratio = 0.742, P = 0.012) versus placebo-Rd (20.6 vs. 14.7 months in the median) (data cut-off as of October 30, 2014). Ixazomib has been approved by the United States Food and Drug Administration in November 2015, and the European Medicines Agency in November 2016 for the treatment of multiple myeloma (MM) patients who have received at least one prior therapy. In Japan, ixazomib was approved for the treatment of relapsed and/or refractory MM in March, 2017. It is expected to demonstrate that the oral proteasome inhibitor ixazomib is an effective and convenient treatment option in clinical practice.
Ixazomib: A Review in Relapsed and/or Refractory Multiple Myeloma. [2018]The oral proteasome inhibitor ixazomib (Ninlaro®) is approved in the USA, EU and Japan in combination with lenalidomide and dexamethasone, for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy. In adults with relapsed and/or refractory MM who had received one to three prior therapies, progression-free survival (PFS) was significantly prolonged in patients who received the ixazomib- versus placebo-based triple therapy in the pivotal, global TOURMALINE-MM1 trial and its regional expansion (China continuation study). A significantly longer time to progression and favourable hazard ratios for PFS were observed across all prespecified subgroups, including patients with high cytogenetic risk. Overall response was achieved in a significantly higher proportion of patients receiving ixazomib- than placebo-based treatment. Ixazomib had a manageable tolerability profile in patients with MM. Ixazomib is the first orally-administered proteasome inhibitor approved for patients with MM, and in combination with lenalidomide and dexamethasone represents an important new option for use in patients with relapsed and/or refractory MM who have previously received at least one prior therapy.
The investigational proteasome inhibitor ixazomib for the treatment of multiple myeloma. [2015]Ixazomib is an investigational, reversible 20S proteasome inhibitor. It is the first oral proteasome inhibitor under clinical investigation in multiple myeloma (MM). Under physiological conditions, the stable citrate ester drug substance, ixazomib citrate (MLN9708), rapidly hydrolyzes to the biologically active boronic acid, ixazomib (MLN2238). Preclinical studies have demonstrated antitumor activity in MM cell lines and xenograft models. In Phase I/II clinical studies ixazomib has had generally manageable toxicities, with limited peripheral neuropathy observed to date. Preliminary data from these studies indicate ixazomib is active as a single agent in relapsed/refractory MM and as part of combination regimens in newly diagnosed patients. Phase III studies in combination with lenalidomide-dexamethasone are ongoing.
Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. [2022]Ixazomib is an oral proteasome inhibitor that is currently being studied for the treatment of multiple myeloma.