Pomalidomide for Kaposi Sarcoma

Not currently recruiting at 17 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

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

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

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

Compensation: Varies

Number of Visits: 7

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how pomalidomide, a cancer-fighting drug, acts against Kaposi sarcoma, a cancer that causes skin lesions. The researchers aim to determine if pomalidomide can inhibit blood vessel growth, enhance the immune system, and kill cancer cells. The trial suits individuals diagnosed with Kaposi sarcoma who have at least five measurable skin lesions and know their HIV status. Participants will undergo regular check-ups, including blood tests and possibly a biopsy, to monitor the treatment's effects. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

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.

Is there any evidence suggesting that pomalidomide is likely to be safe for humans?

Research has shown that pomalidomide is generally safe for people with Kaposi sarcoma. Studies have found that patients tolerate this cancer-fighting drug well, regardless of HIV status. Importantly, no new safety concerns have emerged. The safety profile of pomalidomide for treating Kaposi sarcoma aligns with its use in other conditions, with side effects as expected and no new issues appearing. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Pomalidomide is unique because it offers a new approach for treating Kaposi Sarcoma by modulating the immune system and inhibiting tumor growth. Most traditional treatments for Kaposi Sarcoma, like chemotherapy and antiretroviral therapy, do not target the immune pathways as directly as pomalidomide does. Researchers are excited about pomalidomide because it could potentially offer a more targeted therapy with fewer side effects, improving patient outcomes and quality of life.

What evidence suggests that pomalidomide might be an effective treatment for Kaposi sarcoma?

Research shows that pomalidomide, the treatment under study in this trial, effectively treats Kaposi sarcoma (KS), a type of skin cancer. Studies have found that 71% of patients experience a reduction in cancer symptoms. Pomalidomide stops the growth of blood vessels that supply the cancer, boosts the immune system, and may kill cancer cells. It is generally well-tolerated, causing no severe side effects for most people. Importantly, its effectiveness remains consistent regardless of HIV status, making it suitable for various KS patients. ^{1 6 7 8 9}

Who Is on the Research Team?

Samantha L Vogt

Principal Investigator

AIDS Malignancy Consortium

Are You a Good Fit for This Trial?

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.

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.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Pomalidomide

Trial Overview 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.

How Is the Trial Designed?

Group I: Treatment (pomalidomide) Experimental Treatment 5 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

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A 72-year-old male developed serious lung injury, characterized by dyspnea and ground glass opacities, two months after starting treatment with pomalidomide for multiple myeloma, highlighting a potential adverse effect of this drug.

Discontinuing pomalidomide led to a rapid recovery of symptoms and CT-scan abnormalities, suggesting that recognizing and addressing pomalidomide-induced lung injury is crucial for patient safety, especially as its use increases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide-induced lung injury: A case report. Vivien, A., Ancel, J., Godet, S., et al.[2023]

Pomalidomide, when combined with low-dose dexamethasone, significantly improves progression-free survival and overall survival in adults with relapsed and refractory multiple myeloma, based on results from multinational phase II and III studies involving patients who had undergone at least two prior treatments.

The treatment has a manageable safety profile, with the most common serious side effects being neutropenia, infections, anemia, and thrombocytopenia, making it a viable option for patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: A Review in Relapsed and Refractory Multiple Myeloma. Hoy, SM.[2018]

Lenalidomide has demonstrated clinical effectiveness in treating patients with Kaposi sarcoma associated with HIV, highlighting its potential as a therapeutic option for this difficult-to-treat cancer.

This finding suggests that immunomodulatory imine drugs like lenalidomide could be valuable additions to the treatment arsenal for managing Kaposi sarcoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lenalidomide and the Expanding Toolkit to Manage Kaposi Sarcoma. Henry, DH., Maki, RG.[2022]

Pomalidomide has been approved in the USA for treating relapsed and refractory multiple myeloma in combination with low-dose dexamethasone, showing efficacy after at least two prior therapies.

The drug is also undergoing clinical trials for various other conditions, including myelofibrosis and systemic sclerosis, indicating its potential as a versatile treatment option in hematological and connective tissue diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide: first global approval. Elkinson, S., McCormack, PL.[2022]

Pomalidomide, an oral immune modulatory agent, was found to be well tolerated and effective in treating Kaposi's sarcoma (KS) in a study of 22 patients, with a response rate of 73%, including 60% in HIV-infected patients and 100% in HIV-uninfected patients.

The treatment led to rapid responses, with a median time to response of 4 weeks, and improved health-related quality of life, indicating its potential as a viable therapy for KS, especially in resource-limited settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study. Polizzotto, MN., Uldrick, TS., Wyvill, KM., et al.[2022]

Pomalidomide, an anti-angiogenic therapy that inhibits VEGF, has been recently approved by the FDA and shows promise for treating refractory Kaposi's sarcoma (KS), which is important as many patients do not respond to standard chemotherapy.

Immune checkpoint blockade is a potential alternative treatment for KS by restoring immunity against HHV-8, but currently lacks marketing approval, highlighting the need for more clinical trials to evaluate the efficacy and safety of these therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Perspectives in the Systemic Treatment of Kaposi's Sarcoma. Valantin, MA., Royston, L., Hentzien, M., et al.[2022]

Pomalidomide is an effective treatment for relapsed and refractory multiple myeloma (RRMM), showing significant responses even in patients resistant to other treatments like lenalidomide and bortezomib.

Combining pomalidomide with low-dose dexamethasone has been shown to improve progression-free survival and overall survival compared to higher doses of dexamethasone or using pomalidomide alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide. Engelhardt, M., Ajayi, S., Reinhardt, H., et al.[2019]

A study involving 48 healthy subjects demonstrated that the generic drug pomalidomide is bioequivalent to the originator product Imnovid®, with similar pharmacokinetic parameters in both fasting and fed states.

Both pomalidomide and Imnovid® exhibited comparable safety profiles, with similar incidence and severity of adverse events, indicating that the generic version is a safe alternative to the branded drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and bioequivalence of two pomalidomide capsules in healthy chinese subjects under fasting and fed conditions. Liu, Z., Xu, Z., Gao, Z., et al.[2023]

In a phase II trial involving 12 HIV-infected men with progressive Kaposi's sarcoma (KS) who had previously undergone chemotherapy, lenalidomide showed a 40% response rate according to ACTG criteria at week 48, although no responses were observed using the Physical Global Assessment (PGA) criteria.

Lenalidomide was generally well tolerated, with only one patient discontinuing due to hives and another patient dying during the study; however, 14 grade 3-4 adverse events were reported, indicating the need for careful monitoring in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Trial of Lenalidomide in HIV-Infected Patients with Previously Treated Kaposi's Sarcoma: Results of the ANRS 154 Lenakap Trial. Pourcher, V., Desnoyer, A., Assoumou, L., et al.[2021]

In a study of 19 participants with Kaposi sarcoma, those with HIV had significantly lower CD4+ T-cell counts and fewer senescent CD8+ T cells compared to those without HIV, highlighting the impact of HIV on immune function.

Treatment with pomalidomide for three cycles resulted in increased activation of CD4+ and CD8+ T cells and decreased senescent T cells, suggesting that pomalidomide enhances immune response in Kaposi sarcoma patients, potentially contributing to its therapeutic effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunophenotypic analysis in participants with Kaposi sarcoma following pomalidomide administration. Lurain, K., Polizzotto, MN., Krug, LT., et al.[2023]

In a phase I study involving 23 patients with metastatic pancreatic cancer, the combination of pomalidomide and gemcitabine was found to be feasible and safe, with a maximum tolerated dose of 10 mg/day for pomalidomide.

While not the primary focus, the treatment showed promising signs of efficacy, with 15% of patients achieving partial responses and 50% experiencing significant decreases in CA 19-9 levels, a marker for pancreatic cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I, dose-escalation study of pomalidomide (CC-4047) in combination with gemcitabine in metastatic pancreas cancer. Infante, JR., Jones, SF., Bendell, JC., et al.[2022]

Pomalidomide, an oral medication, showed a 71% overall response rate in treating Kaposi sarcoma (KS) among 28 participants, including both HIV-positive and HIV-negative individuals, indicating its efficacy as a treatment option.

The treatment was found to be safe, although 50% of participants experienced grade 3 neutropenia, and the median progression-free survival was 10.2 months, suggesting it could be a viable alternative to traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection. Ramaswami, R., Polizzotto, MN., Lurain, K., et al.[2022]

Pomalidomide, an immunomodulatory agent derived from thalidomide, has shown significant anti-cancer effects in patients with relapsed and refractory multiple myeloma, particularly in those resistant to other treatments like lenalidomide and bortezomib.

Combination therapy with pomalidomide and low-dose dexamethasone has demonstrated improved response rates and survival outcomes compared to higher doses of dexamethasone or pomalidomide alone, leading to further investigations into its use with various other anti-myeloma agents.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pomalidomide. Engelhardt, M., Wäsch, R., Reinhardt, H., et al.[2015]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34862247/

Safety, Activity, and Long-term Outcomes of Pomalidomide in ... The overall response rate was 71%: 95% confidence interval (CI) 51%-87%. Twelve of 18 HIV-positive (67%; 95% CI, 41-87%) and 8 of 10 HIV- ...

2. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)01356-5/fulltext

MO41-5 Efficacy of pomalidomide in patients with kaposi ... All studies demonstrated that pomalidomide is a well-tolerated and effective immunomodulatory drug for KS treatment regardless of HIV status. K. Lurain (2023) ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8898289/

Safety, activity, and long-term outcomes of pomalidomide in ... Pomalidomide is a safe and active chemotherapy-sparing agent for the treatment of KS among individuals with or without HIV.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01495598

NCT01495598 | Pomalidomide for Kaposi Sarcoma in ... Researchers want to see if pomalidomide can treat Kaposi sarcoma, a rare and potentially fatal skin cancer.

5. accc-cancer.org accc-cancer.org/docs/ossn-network/industry-news-announcements/pomalyst-ks-launch-letter---state-societies.pdf?sfvrsn=80d4c5d6_2&

POMALYST (pomalidomide) capsules approved to treat ... POMALYST efficacy in Kaposi sarcoma (KS)1. POMALYST 5 mg once daily orally ... In the Kaposi sarcoma (KS) trial, hematologic toxicities were the most ...

6. ccr.cancer.gov ccr.cancer.gov/news/article/fda-approves-pomalidomide-for-aids-related-kaposi-sarcoma

FDA approves pomalidomide for AIDS-related Kaposi sarcoma “Pomalyst has shown positive results in Kaposi sarcoma patients, regardless of their HIV status,” said Dr. Yarchoan. “Also, it provides a ...

7. news.bms.com news.bms.com/news/corporate-financial/2020/US-Food-and-Drug-Administration-Approves-Bristol-Myers-Squibbs-Pomalyst-pomalidomide-for-AIDS-Related-and-HIV-Negative-Kaposi-Sarcoma/default.aspx

U.S. Food and Drug Administration Approves ... No new safety signals were identified, and the safety of Pomalyst in Kaposi sarcoma was consistent with the known safety profile of Pomalyst in ...

8. aacrjournals.org aacrjournals.org/clincancerres/article-abstract/28/5/840/681694

Safety, Activity, and Long-term Outcomes of Pomalidomide in ... Safety, Activity, and Long-term Outcomes of Pomalidomide in the Treatment of Kaposi Sarcoma among Individuals with or without HIV Infection Available. Ramya ...

9. ascopubs.org ascopubs.org/doi/10.1200/jco.2013.31.15_suppl.tps10595

Phase I/II study of the safety, pharmacokinetics, and ... Phase I/II study of the safety, pharmacokinetics, and efficacy of pomalidomide in the treatment of Kaposi sarcoma in individuals with or without HIV.