Pomalidomide for Kaposi Sarcoma

Recruiting at 15 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

45 Participants Needed

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. ^{1 2 3 4 5}

Is 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). ^{6 7 8 9 10}

What 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. ^{1 2 11 12 13}

Research Team

Samantha L Vogt

Principal Investigator

AIDS Malignancy Consortium

Eligibility 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.

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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, 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]

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]

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]

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]

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 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]

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 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]

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]

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, 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]

References

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

Pomalidomide for Symptomatic Kaposi's Sarcoma in People With and Without HIV Infection: A Phase I/II Study. [2022]

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

Pomalidomide-induced lung injury: A case report. [2023]

3. Germany pubmed.ncbi.nlm.nih.gov

Pomalidomide. [2015]

4. Germany pubmed.ncbi.nlm.nih.gov

Pomalidomide. [2019]

5. England pubmed.ncbi.nlm.nih.gov

A phase I, dose-escalation study of pomalidomide (CC-4047) in combination with gemcitabine in metastatic pancreas cancer. [2022]

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

Lenalidomide and the Expanding Toolkit to Manage Kaposi Sarcoma. [2022]

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

Immunophenotypic analysis in participants with Kaposi sarcoma following pomalidomide administration. [2023]

8. United States 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. [2021]

9. United States 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. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic Perspectives in the Systemic Treatment of Kaposi's Sarcoma. [2022]

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

Pharmacokinetics and bioequivalence of two pomalidomide capsules in healthy chinese subjects under fasting and fed conditions. [2023]

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

Pomalidomide: first global approval. [2022]

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

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