HyBryte Cream for Cutaneous T-Cell Lymphoma

(FLASH2 Trial)

Recruiting at 17 trial locations

Overseen By Jennifer Bonfrisco

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Soligenix

Must not be taking: Topical steroids, Systemic steroids

Disqualifiers: Sun hypersensitivity, Allergy to HyBryte, others

Pivotal Trial (Near Approval)

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

To evaluate the use of HyBryte, a topical photosensitizing agent, to treat patients with patch/plaque phase cutaneous T-cell lymphoma (mycosis fungoides).

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications before enrolling. You must stop using topical treatments for CTCL at least 2 weeks before, and systemic treatments like steroids or light therapy at least 4 weeks before joining the study.

What data supports the effectiveness of the treatment HyBryte for cutaneous T-cell lymphoma?

Research shows that synthetic hypericin, a component of HyBryte, used in photodynamic therapy (a treatment using light to activate a drug) has been effective in treating early-stage cutaneous T-cell lymphoma with minimal side effects. ^{1 2 3 4 5}

Is HyBryte Cream safe for use in humans?

HyBryte Cream, also known as synthetic hypericin, has been studied for safety in treating cutaneous T-cell lymphoma. It is a novel therapy that uses light activation and is noted for having minimal short- and long-term adverse effects. ^{1 3 5 6 7}

What makes HyBryte cream unique for treating cutaneous T-cell lymphoma?

HyBryte cream is unique because it uses synthetic hypericin activated by visible light as a novel photodynamic therapy, which is nonmutagenic (does not cause genetic mutations) and aims to minimize adverse effects compared to traditional treatments. ^{2 3 5 8 9}

Eligibility Criteria

This trial is for individuals with a specific skin cancer called cutaneous T-cell lymphoma (CTCL), stages IA, IB, or IIA. Participants must have at least three evaluable lesions and not be pregnant or nursing. They should agree to pregnancy testing before treatment and consent to follow the study rules.

Inclusion Criteria

Patients with a minimum of three (3) evaluable, discrete lesions

Patients willing to follow the clinical protocol and voluntarily give their written informed consent

I am not pregnant or nursing and agree to a pregnancy test before treatment.

Exclusion Criteria

I haven't used topical treatments on my skin cancer lesions for 2 weeks.

History of allergy or hypersensitivity to any of the components of HyBryte

A Screening ECG with a QT interval >470 ms (corrected for heart rate using the Fridericia's formula)

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HyBryte or placebo gel applied twice weekly for 18 weeks, followed by visible light exposure

18 weeks

36 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

3 visits (in-person)

Treatment Details

Interventions

• HyBryte (Photosensitizing Agent)

Trial Overview The trial tests HyBryte™, a topical medication applied directly on the skin, against a placebo in patients with patch/plaque phase CTCL (mycosis fungoides). The goal is to see if HyBryte™ can effectively treat this condition.

Participant Groups

Group I: HyBryte (0.25% Hypericin) Experimental Treatment 1 Intervention

HyBryte gel is applied twice weekly for 18 weeks.

Group II: Placebo Placebo Group 1 Intervention

Placebo gel is indistinguishable from HyBryte gel, and is applied twice weekly for 18 weeks.

Who Is Running the Clinical Trial?

Soligenix

Lead Sponsor

Trials

12

Recruited

900+

Findings from Research

In a clinical trial involving 67 adults with early-stage cutaneous T-cell lymphoma (CTCL), topical bexarotene gel demonstrated a 63% overall response rate, indicating its efficacy in treating this condition.

The gel was well tolerated by most patients, with mild to moderate side effects primarily limited to the application sites, and a median response duration of 99 weeks, suggesting it is a viable long-term treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 and 2 trial of bexarotene gel for skin-directed treatment of patients with cutaneous T-cell lymphoma. Breneman, D., Duvic, M., Kuzel, T., et al.[2019]

Bexarotene gel is effective in resolving mycosis fungoides (MF) lesions and may work even better when combined with topical steroids or phototherapy, making it a promising treatment for early-stage patients.

DAB(389)IL-2 has shown a 30% remission rate in highly refractory CTCL patients, but due to potential side effects like capillary leak syndrome, it is reserved for advanced cases and requires careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bexarotene and DAB(389)IL-2 (denileukin diftitox, ONTAK) in treatment of cutaneous T-cell lymphomas: algorithms. Duvic, M.[2019]

Bexarotene gel is a new topical treatment for early-stage cutaneous T-cell lymphomas (CTCL) that has shown efficacy in patients with stage IA or IB disease, especially those who have not responded to or cannot tolerate traditional therapies.

This treatment is generally well tolerated and offers a more convenient administration compared to traditional skin-directed therapies, which often have significant side effects like skin damage and secondary malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bexarotene gel: a new skin-directed treatment option for cutaneous T-cell lymphomas. Martin, AG.[2018]

Patients with cutaneous T-cell lymphoma who have aggressive features, such as cutaneous tumors or lymph node involvement, typically experience rapid disease progression and shorter survival rates.

Allogeneic hematopoietic stem cell transplant (HSCT) offers the only potentially curative treatment option, providing durable long-term remissions compared to high-dose chemotherapy, which often leads to recurrence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose therapy and bone marrow transplantation in cutaneous T-cell lymphoma. Oyama, Y., Guitart, J., Kuzel, TM., et al.[2019]

In a phase 3 clinical trial involving 169 patients with early-stage mycosis fungoides-cutaneous T-cell lymphoma (MF/CTCL), topical synthetic hypericin ointment activated by visible light showed a significant improvement in lesion response rates compared to placebo, with a 16% response rate after 6 weeks, increasing to 49% after 3 treatment cycles.

The treatment demonstrated a favorable safety profile, with only mild local skin reactions reported and no serious adverse events, making it a promising nonmutagenic photodynamic therapy option for patients with early-stage MF/CTCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Topical Hypericin Photodynamic Therapy for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides): The FLASH Phase 3 Randomized Clinical Trial. Kim, EJ., Mangold, AR., DeSimone, JA., et al.[2023]

In a retrospective study of 21 patients treated with bexarotene for refractory cutaneous T-cell lymphoma (CTCL), the overall response rate was 81%, with early-stage patients showing a complete response rate of 100% compared to 77.8% in advanced-stage patients.

Despite the high response rate, the study revealed a concerning overall mortality rate of 52.8%, particularly in advanced-stage patients, indicating that bexarotene may not be effective for all stages of CTCL and suggesting a need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polish Lymphoma Research Group Experience With Bexarotene in the Treatment of Cutaneous T-Cell Lymphoma. Sokolowska-Wojdylo, M., Florek, A., Zaucha, JM., et al.[2018]

Vorinostat is an effective treatment for advanced cutaneous T-cell lymphoma (CTCL), showing a 30% overall response rate in Phase II studies, with significant reductions in skin lesions and a time to response of about 10 weeks.

The drug is generally well tolerated at the approved dose of 400 mg once daily, with common mild side effects like fatigue and nausea, and severe toxicities occurring in less than 6% of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vorinostat: A novel therapy for the treatment of cutaneous T-cell lymphoma. Kavanaugh, SM., White, LA., Kolesar, JM.[2022]

Phototherapy, especially with treatments like broadband UVB and narrowband UVB, is effective for early-stage cutaneous T-cell lymphoma (CTCL), but it carries risks such as sunburn and potential skin damage.

Combining phototherapy with systemic treatments like IFN-alpha and retinoids can improve treatment outcomes and reduce the required doses of phototherapy, while extracorporeal photopheresis is beneficial for more advanced cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of phototherapy in cutaneous T-cell lymphoma. Pothiawala, SZ., Baldwin, BT., Cherpelis, BS., et al.[2010]

Cutaneous T-cell lymphoma (CTCL) treatment is tailored to the specific stage and type of the disease, with early-stage therapies including phototherapy and local steroids, while higher stages may require systemic treatments like interferon alpha and bexarotene.

Due to high relapse rates in advanced CTCL, new treatment options are needed, and the fusion protein brentuximab-vedotin, which targets CD30, shows promising potential in clinical studies for improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treatment of mycosis fungoides and Sézary syndrome]. Nicolay, JP., Assaf, C.[2022]

References

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

Phase 1 and 2 trial of bexarotene gel for skin-directed treatment of patients with cutaneous T-cell lymphoma. [2019]

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

Bexarotene and DAB(389)IL-2 (denileukin diftitox, ONTAK) in treatment of cutaneous T-cell lymphomas: algorithms. [2019]

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

Bexarotene gel: a new skin-directed treatment option for cutaneous T-cell lymphomas. [2018]

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

High-dose therapy and bone marrow transplantation in cutaneous T-cell lymphoma. [2019]

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

Efficacy and Safety of Topical Hypericin Photodynamic Therapy for Early-Stage Cutaneous T-Cell Lymphoma (Mycosis Fungoides): The FLASH Phase 3 Randomized Clinical Trial. [2023]

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

Polish Lymphoma Research Group Experience With Bexarotene in the Treatment of Cutaneous T-Cell Lymphoma. [2018]

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

Vorinostat: A novel therapy for the treatment of cutaneous T-cell lymphoma. [2022]

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

The role of phototherapy in cutaneous T-cell lymphoma. [2010]

9. Germany pubmed.ncbi.nlm.nih.gov

[Treatment of mycosis fungoides and Sézary syndrome]. [2022]