Pomalidomide for Kaposi Sarcoma
Recruiting in Palo Alto (17 mi)
+15 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must be taking: Antiretroviral therapy
Must not be taking: Zidovudine, Erythropoietin, Corticosteroids
Disqualifiers: Visceral KS, Allergic reactions, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?This phase II trial studies the effect of pomalidomide in treating patients with Kaposi sarcoma. Pomalidomide is a cancer fighting drug that stops the growth of blood vessels, stimulates the immune system, and may kill cancer cells.
Will I have to stop taking my current medications?
The trial does not specify if you must stop taking your current medications, but certain medications are prohibited, such as those containing zidovudine and strong inhibitors of specific enzymes. It's important to discuss your current medications with the trial team to ensure there are no interactions.
What data supports the effectiveness of the drug pomalidomide for treating Kaposi Sarcoma?
In a study, pomalidomide was shown to be effective in treating Kaposi Sarcoma, with 73% of patients responding to the treatment. It was well tolerated and improved patients' quality of life, regardless of their HIV status.
12345Is pomalidomide safe for humans?
Pomalidomide, used for treating Kaposi Sarcoma, is generally considered safe in humans, but like any medication, it can have side effects. It is an oral drug that modifies the immune system and has been approved by the FDA for its anti-angiogenic activity (reducing blood vessel growth in tumors).
678910What makes the drug pomalidomide unique for treating Kaposi Sarcoma?
Pomalidomide is unique for treating Kaposi Sarcoma because it is an oral drug that modulates the immune system, making it suitable for patients with or without HIV. It offers a new option for those with advanced disease who have already tried other treatments, and it can be administered in resource-limited settings.
12111213Eligibility Criteria
Adults with confirmed Kaposi Sarcoma (KS) and measurable disease, who understand the trial and consent to participate. They must have proper organ function, a life expectancy over 6 months, stable HIV treatment if positive, and agree to REMS program for drug safety. Pregnant women, those with certain heart conditions or mental illnesses that affect compliance, prior use of similar drugs like thalidomide or active infections are excluded.Inclusion Criteria
My bilirubin levels are within the normal range, or slightly higher if I'm on certain medications.
Participants must agree to participate in and comply with the mandatory POMALYST Risk Evaluation and Mitigation Strategy (REMS) program
Your AST and ALT levels in your blood should be below 2.5 times the normal limit.
+18 more
Exclusion Criteria
I haven't had chemotherapy, radiotherapy, or specific treatments for KS lesions in the last 4 to 6 weeks, except for ART.
You have a known condition that makes your blood clot more easily.
I have previously used pomalidomide, lenalidomide, or thalidomide.
+12 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive pomalidomide orally once daily on days 1-21, repeated every 28 days for up to 12 cycles
12 months
Monthly visits (in-person)
Extended Treatment
Participants with complete or partial response continue pomalidomide for an additional 12 cycles
12 months
Monthly visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
Up to 5 years
Every 6 months (in-person)
Participant Groups
The trial is testing pomalidomide's effectiveness on KS patients. Pomalidomide aims to halt blood vessel growth in tumors, boost the immune system response against cancer cells and may directly kill them. The study involves CT scans, X-rays, biopsies and biospecimen collection to assess this effect.
1Treatment groups
Experimental Treatment
Group I: Treatment (pomalidomide)Experimental Treatment5 Interventions
Patients receive pomalidomide PO QD on days 1-21. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. After 12 cycles, patients with CR or PR continue pomalidomide for an additional 12 cycles with the option to continue thereafter in the absence of disease progression or unacceptable toxicity. After 12 cycles, patients with stable disease may continue pomalidomide for an additional 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo chest x-ray imaging throughout the trial. Patients may undergo CT as clinically indicated. Patients also undergo blood sample collection and may optionally undergo tissue biopsy during screening and on the trial.
Pomalidomide is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as Pomalyst for:
- Multiple myeloma
- Kaposi's sarcoma
🇪🇺 Approved in European Union as Imnovid for:
- Multiple myeloma
- Kaposi's sarcoma
🇨🇦 Approved in Canada as Pomalyst for:
- Multiple myeloma
- Kaposi's sarcoma
🇯🇵 Approved in Japan as Imnovid for:
- Multiple myeloma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Montefiore Medical Center-Einstein CampusBronx, NY
Virginia Mason Medical CenterSeattle, WA
Thomas Street at Quentin Mease Health CenterHouston, TX
Siteman Cancer Center at Washington UniversitySaint Louis, MO
More Trial Locations
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study. [2022]Purpose Kaposi's sarcoma (KS) is a multicentric tumor caused by Kaposi's sarcoma-associated herpesvirus. Unmet needs include therapies that are oral, anthracycline sparing, and deliverable in resource-limited settings. We evaluated pomalidomide, an oral immune modulatory agent, in patients with symptomatic KS. Methods The primary objectives were to assess tolerability, pharmacokinetics, and activity. Initial dosage level was 5 mg once per day for 21 days per 28-day cycle, with a de-escalated level of 3 mg if not tolerable, and aspirin 81 mg once per day thromboprophylaxis. HIV-infected patients required controlled viremia with either persistent KS despite 3 months of antiretroviral therapy (ART) or progressive KS despite 2 months of ART. Evaluations included tumor response and health-related quality of life (HRQL). Results Twenty-two patients were treated; 15 (68%) were HIV infected, 17 (77%) had advanced (T1) disease, and 19 (86%) previous KS therapy excluding ART. All were treated with 5 mg because no dose-limiting toxicities occurred. Over 156 cycles, the grade 3/4 adverse events possibly attributable to therapy were neutropenia (23 cycles, 10 patients), infection (1 cycle), and edema (1 cycle). Sixteen patients responded (73%; 95% CI, 50% to 89%): nine of 15 HIV-infected patients (60%; 95% CI, 32% to 84%) and all seven HIV-uninfected patients (100%; 95% CI, 59% to 100%). Median time to response was 4 weeks (range, 4 to 36 weeks). HRQL showed no impairment during therapy and improved satisfaction with appearance at end therapy ( P = .03). Significant increases in CD4+ and CD8+ cells were seen in patients with and without HIV, together with a transient increase in Kaposi's sarcoma-associated herpesvirus viral load at week 4 ( P = .05). Conclusion Pomalidomide is well tolerated and active in KS regardless of HIV status. Responses were rapid, with improved self-reported outcomes, and occurred in advanced and heavily pretreated disease. Correlative studies support, at least in part, an immunologic mechanism of activity.
Pomalidomide-induced lung injury: A case report. [2023]Pomalidomide is an immunomodulatory imide drug used in multiple myeloma and in Kaposi sarcoma.
Pomalidomide. [2015]Pomalidomide (originally CC-4047 or 3-amino-thalidomide) is a derivative of thalidomide that is antiangiogenic and also acts as an immunomodulator. Pomalidomide, as the newest immunomodulatory agent (IMiD), has shown substantial in vitro antiproliferative and proapoptotic effects. In vivo studies have suggested limited cross-resistance between lenalidomide and pomalidomide, and the response of pomalidomide in relapsed and refractory (RR) multiple myeloma (MM) patients, including those who are refractory to both lenalidomide and bortezomib, has induced notable enthusiasm. Several studies have evaluated continuous (2 mg/day) or alternate (5 mg/2 day) dose schedules of pomalidomide, as well as 2 versus 4 mg schedules, and pomalidomide alone versus in combination with dexamethasone or other antimyeloma agents. Since pomalidomide plus low-dose dexamethasone has shown better responses, progression-free and overall survival than high-dose dexamethasone or pomalidomide alone, subsequent trials investigating pomalidomide combination therapy have been initiated. Among these trials combinations with alkylating agents (cyclophosphamide, bendamustin), anthracyclins (pegylated liposomal doxorubicin), proteasome inhibitors (bortezomib, carfilzomib), and various others can be found. Pomalidomide has also been assessed in AL amyloidosis, MPNs (myelofibrosis [MF]), Waldenstrom's macroglobulinemia, solid tumors (sarcoma, lung cancer), or HIV and--for AL amyloidosis and MF--has already proven remarkable activity. Due to its potency, pomalidomide was approved by the US Food and Drug Administration (FDA) for RRMM in 2/2013 and has also been approved by the European Medicines Agency (EMA).
Pomalidomide. [2019]Pomalidomide (originally CC-4047 or 3-amino-thalidomide) is a derivative of thalidomide that is antiangiogenic and also acts as immunomodulatory. Pomalidomide, the recent immunomodulatory agent (IMiD), has shown substantial in vitro antiproliferative and proapoptotic effects. In vivo studies have suggested limited cross-resistance between lenalidomide and pomalidomide. Moreover, pomalidomide achieved very convincing responses in relapsed and refractory multiple myeloma (RRMM) patients, including those, who are refractory to both lenalidomide and bortezomib. Since pomalidomide plus low-dose dexamethasone has shown better responses, progression-free survival (PFS) and overall survival (OS) than high-dose dexamethasone or pomalidomide alone, subsequent trials have pursued or are still investigating pomalidomide triplet combinations, using cyclophosphamide or other novel agents, such as proteasome inhibitors (PI: bortezomib, carfilzomib) or antibodies, like elotuzumab or daratumumab. Pomalidomide has also been assessed in AL amyloidosis, MPNs (myelofibrosis [MF]), Waldenstrom's macroglobulinemia, solid tumors (sarcoma, lung cancer), or HIV, and-for AL amyloidosis and MF-has already been proven to be remarkably active. Due to its potency, pomalidomide was approved for RRMM by the US Food and Drug Administration (FDA) and by the European Medicines Agency (EMA) in 2013 and for drug combination with low-dose dexamethasone in 2015. In June 2017, the FDA further expanded approval for pomalidomide in combination with daratumumab and low-dose dexamethasone for patients with RRMM.
A phase I, dose-escalation study of pomalidomide (CC-4047) in combination with gemcitabine in metastatic pancreas cancer. [2022]Pomalidomide is an investigational immunomodulating drug (IMiD) that also inhibits angiogenesis and has direct anti-tumour effects. This phase I study was performed to identify the optimal dose of pomalidomide to be used in combination with gemcitabine in the treatment of patients with metastatic pancreatic cancer.
Lenalidomide and the Expanding Toolkit to Manage Kaposi Sarcoma. [2022]Lenalidomide recently was shown to have clinical activity in patients with human immunodeficiency virus-associated Kaposi sarcoma. Immunomodulatory imine drugs thus provide another tool in the treatment of this challenging neoplasm. See related article by Reid et al., p. 2646.
Immunophenotypic analysis in participants with Kaposi sarcoma following pomalidomide administration. [2023]The aim of this study was to evaluate baseline differences by HIV status and the impact of pomalidomide on lymphocyte counts and T-cell subsets in patients with Kaposi sarcoma.
Phase II Trial of Lenalidomide in HIV-Infected Patients with Previously Treated Kaposi's Sarcoma: Results of the ANRS 154 Lenakap Trial. [2021]Lenalidomide, an oral immunomodulating agent, has shown promising activity in HIV-infected individuals with Kaposi's sarcoma (KS). This single-arm, multicenter, open-label, Gehan's two-stage phase II trial evaluated the efficacy and safety of lenalidomide in HIV-infected patients with progressive KS despite previous chemotherapy (NCT01282047, ANRS 154 Lenakap trial). The primary endpoint was the rate of partial response (PR) or complete response (CR) at week 24, evaluated by both the study investigators and the patients using the Physical Global Assessment (PGA). AIDS Clinical Trials Group (ACTG) criteria for KS treatment evaluation were used as a secondary endpoint. The data and safety monitoring board recommended that enrollments be halted on April 24, 2013, because of lack of responses. We enrolled 12 antiretroviral-treated HIV-infected men with progressive KS despite previous chemotherapy. Their HIV plasma viral load was <50 copies/ml and their median CD4 cell count 444/mm3. One patient stopped taking lenalidomide because of hives at week 1 and a second patient died at week 7. The remaining 10 patients were assessable at week 24, when none had PGA-defined CR or PR and one had ACTG-defined PR. There were no additional PGA responses at week 48, but an additional three patients had ACTG responses, for a total of four patients with ACTG PR at week 48 (40%; 95% confidence interval: 12.2-73.8). Fourteen grade 3-4 adverse events were considered at least possibly related to lenalidomide during a total of 101 cycles. Lenalidomide was well tolerated in antiretroviral experienced patients with progressive KS previously treated with chemotherapy. The ACTG-defined response rate at week 48 was 40%, while it was 0% using PGA criteria.
Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection. [2022]Kaposi sarcoma (KS) is caused by Kaposi sarcoma herpesvirus (KSHV), also known as human herpesvirus 8 (HHV-8). KS, which develops most frequently among people with HIV, is generally treated with chemotherapy, but these drugs have acute and cumulative toxicities. We previously described initial results of a trial of pomalidomide, an oral immunomodulatory derivative of thalidomide, in patients with KS. Here, we present results on the full cohort and survival outcomes.
Therapeutic Perspectives in the Systemic Treatment of Kaposi's Sarcoma. [2022]In patients with Kaposi's sarcoma (KS), the therapeutic goal is to achieve a durable remission in the size and number of skin and visceral lesions. Although most patients show tumor regression in response to standard systemic chemotherapy regimens, alternative systemic treatments are needed for patients who develop refractory KS. Anti-angiogenic therapies represent attractive therapeutic targets in this context, due to the central role of angiogenesis in KS pathogenesis. Pomalidomide, which exhibits such anti-angiogenic activity through inhibition of VEGF, currently constitutes the most promising agent of this class and has been recently approved by the FDA. In addition, immune checkpoint blockade also represents an interesting alternative therapeutic approach through the restoration of immunity against HHV-8, the causative agent of KS, and improvement of tumor control. Although small series of cases treated successfully with these drugs have been reported, there is no marketing approval for anti-immune checkpoint antibodies for KS to date. In the present review, we will discuss potential therapeutic options for patients with recurrent or refractory KS, including systemic chemotherapies, immune checkpoint inhibitors, anti-herpesvirus agents, and anti-angiogenic drugs. Well-conducted clinical trials in this population are urgently needed to correctly address the efficacy of targeted agents and immunomodulators, while monitoring for adverse effects.
Pharmacokinetics and bioequivalence of two pomalidomide capsules in healthy chinese subjects under fasting and fed conditions. [2023]Imnovid® is an immunomodulatory drug with antineoplastic activity. The aim of this study was to evaluate the bioequivalence and safety of the generic drug pomalidomide (Chia Tai Tianqing Pharmaceutical Group Co., Ltd) and its originator product Imnovid® (Celgene Europe Ltd) in the fasting and fed states, respectively.
Pomalidomide: first global approval. [2022]Pomalidomide (Pomalyst(®)) is a small molecule analogue of thalidomide under development with Celgene Corporation for the oral treatment of haematological and connective tissue diseases. Pomalidomide has been approved in the USA and is awaiting approval in the EU for use with low-dose dexamethasone for the treatment of relapsed and refractory multiple myeloma that has progressed following at least two prior therapies, including lenalidomide and bortezomib. The efficacy and safety of pomalidomide as monotherapy in patients with relapsed and refractory multiple myeloma has also been evaluated in a phase III trial. The agent is in phase III clinical development for the treatment of myelofibrosis and in phase II development for systemic sclerosis. Pomalidomide is also being investigated in patients with amyloidosis, prostate cancer, small cell lung cancer, pancreatic cancer, graft-versus-host disease, and Waldenstrom's macroglobulinaemia. This article summarizes the milestones in the development of pomalidomide leading to this first global approval for relapsed and refractory multiple myeloma.
Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. [2018]Pomalidomide (Imnovid®; Pomalyst®), an analogue of thalidomide, is an immunomodulatory agent, with several mechanisms of action (both direct and indirect) thought to be involved in its anti-myeloma activity. Oral pomalidomide is available in several countries for use in combination with low-dose dexamethasone in adults with relapsed and refractory multiple myeloma. In multinational, phase II or III studies in patients with refractory, or relapsed and refractory multiple myeloma who had received ≥ 2 prior treatment regimens (including ≥ 2 cycles of both lenalidomide and bortezomib), pomalidomide plus low-dose dexamethasone was associated with prolonged progression-free survival (PFS) and overall survival and an improved overall response rate. Pomalidomide plus low-dose dexamethasone had a manageable tolerability profile, with neutropenia, infections, anaemia and thrombocytopenia being the most frequently reported grade 3 or 4 treatment-emergent adverse events. In conclusion, pomalidomide plus low-dose dexamethasone extends the treatment options available for the management of relapsed and refractory multiple myeloma in a patient population that has very limited treatment options.