HyBryte Cream for Cutaneous T-Cell Lymphoma (FLASH2 Trial)
Recruiting in Palo Alto (17 mi)
+13 other locations
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 3
Recruiting
Sponsor: Soligenix
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.
12345Is 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.
13567What 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.
23589Eligibility 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
I have been diagnosed with early-stage cutaneous T-cell lymphoma.
Exclusion Criteria
My skin cancer is at an advanced stage (IIB-IV).
I am not willing to use effective birth control.
I have a history of being on strong immune-suppressing drugs.
I have a history of severe sun sensitivity or related skin conditions.
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: HyBryte (0.25% Hypericin)Experimental Treatment1 Intervention
HyBryte gel is applied twice weekly for 18 weeks.
Group II: PlaceboPlacebo Group1 Intervention
Placebo gel is indistinguishable from HyBryte gel, and is applied twice weekly for 18 weeks.
HyBryte is already approved in United States, European Union, United Kingdom for the following indications:
🇺🇸 Approved in United States as HyBryte for:
- Cutaneous T-cell lymphoma (CTCL)
🇪🇺 Approved in European Union as HyBryte for:
- Cutaneous T-cell lymphoma (CTCL)
🇬🇧 Approved in United Kingdom as HyBryte for:
- Cutaneous T-cell lymphoma (CTCL)
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Mayo ClinicScottsdale, AZ
Dawes Fretzin Dermatology GroupIndianapolis, IN
Washington UniversitySaint Louis, MO
Rochester Skin Lymphoma Medical GroupFairport, NY
More Trial Locations
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Who is running the clinical trial?
SoligenixLead Sponsor
References
Phase 1 and 2 trial of bexarotene gel for skin-directed treatment of patients with cutaneous T-cell lymphoma. [2019]To evaluate the safety, dose tolerance, and efficacy of topical bexarotene gel in patients with early-stage cutaneous T-cell lymphoma (CTCL).
Bexarotene and DAB(389)IL-2 (denileukin diftitox, ONTAK) in treatment of cutaneous T-cell lymphomas: algorithms. [2019]Mycosis fungoides (MF), CD4(+) epidermotropic cutaneous T-cell lymphoma (CTCL), often arises as indolent, inflammatory, chronic, persistent patches and plaques. Conservative and sequential topical therapy patients have the same survival as patients treated with aggressive chemotherapy. Hence, until curative therapy is found, therapies that keep MF in check and prevent progression to more advanced lymphoma may be desirable alternatives and may preserve quality of life. Stage IA patients with stable disease have a very favorable prognosis and often initially receive psoriasis-type therapy. Bexarotene gel, a new topical retinoid X receptor retinoid will resolve MF lesions, reducing dermal T-cell infiltrates when used as a single agent. However, it may be even more effective when combined with topical steroids, with phototherapy (ultraviolet B and psoralen-ultraviolet A), or even with oral bexarotene. The gel may also provide a safe adjunctive therapy for individual lesions that are refractory to other agents, including keratodermas. When more than 10% of the body is involved with CTCL or when adenopathy is present (> stage IB), systemic therapy is indicated. Bexarotene capsules have the advantage of easy oral administration and are extremely effective both for early-stage patients with long-standing extensive plaques and for late-stage patients with Sézary syndrome or large-cell transformation. Monitoring of white blood cell count, lipids, and thyroid function is required. Bexarotene should be tested in combination with interferon-alfa or other therapies such as photopheresis, psoralen-ultraviolet A, and methotrexate and for maintenance after total body skin electron beam. DAB(389)IL-2 is targeted to CD25(+), the interleukin-2 receptor on activated T cells as measured by the expression of CD25. DAB(389)IL-2 has given complete or partial remission in 30% of highly refractory patients with extensive plaques and disfiguring tumors. Because it is effective in killing T cells that surround dermal vessels, cytokine release may occur and result in capillary leak syndrome. Hence, it will be reserved for more advanced and refractory patients and will require intravenous administration and monitoring. The use of oral bexarotene first to reduce dermal infiltrates prior to DAB(389)IL-2 administration might reduce subsequent side effects imparted by this therapy. With three new highly effective agents in the armamentarium for the treatment of CTCL, new combination treatment algorithms can be tested to achieve maximal benefit and quality of life for these patients.
Bexarotene gel: a new skin-directed treatment option for cutaneous T-cell lymphomas. [2018]Cutaneous T-cell lymphomas (CTCLs) are a relatively uncommon group of lymphoproliferative disorders in which a malignant population of T cells is localized to the skin at presentation. Of the 4 classic CTCL phases (patches, infiltrated plaques, tumors, Sézary syndrome), the majority of patients present with early stage patch or plaque disease, which can usually be effectively managed using skin-directed therapies. Traditional skin-directed therapies include topical corticosteroids, topical chemotherapeutic agents (mechlorethamine, carmustine), electron beam therapy (local and total skin), and phototherapy (UV-A, UV-B). Each of these has demonstrated efficacy in early stage disease; however, with the exception of topical corticosteroids, all have some disadvantages and are associated with significant adverse events, particularly secondary skin malignancies and skin damage. Bexarotene is a synthetic retinoid analog that selectively activates retinoid X receptors. In clinical trials, bexarotene gel demonstrated efficacy for the topical treatment of cutaneous lesions in patients with stage IA or IB CTCL who have refractory or persistent disease following other therapies or who cannot tolerate other therapies. Initial evidence indicates that bexarotene gel may be active as first-line therapy in early stage disease. Its role in combination with other treatments remains to be determined. Topical bexarotene gel is generally well tolerated and offers patients greater convenience compared with traditional skin-directed therapies, with a flexible administration regimen. The availability of bexarotene gel provides patients and physicians with a new skin-directed treatment option for early stage CTCL.
High-dose therapy and bone marrow transplantation in cutaneous T-cell lymphoma. [2019]Although most patients who have cutaneous T-cell lymphoma have an indolent clinical course, patients who have cutaneous tumors, lymph node or visceral involvement, or peripheral blood involvement generally have rapidly progressive disease with shorter survival. In those patients with poor prognostic features, conventional combination chemotherapy is usually ineffective. High-dose chemotherapy with autologous hematopoietic stem cell transplant (HSCT) results in high remission rates, but the recurrence is inevitable and rapid. Allogeneic HSCT, in contrast, provides durable long-term remissions and is currently the only potentially curative therapy.
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]Given that mycosis fungoides-cutaneous T-cell lymphoma (MF/CTCL) is chronic, there is a need for additional therapies with minimal short- and long-term adverse effects. Topical synthetic hypericin ointment, 0.25%, activated with visible light is a novel, nonmutagenic photodynamic therapy (PDT).
Polish Lymphoma Research Group Experience With Bexarotene in the Treatment of Cutaneous T-Cell Lymphoma. [2018]Bexarotene, a synthetic retinoid licensed for the treatment of refractory cutaneous T-cell lymphoma (CTCL), has been used clinically in Poland since 2007 in 21 patients. The objective of our retrospective, multicenter study was to evaluate our experience with bexarotene therapy, including efficacy, safety, and survival outcomes. We retrospectively identified 21 adult patients who were treated with bexarotene between the years 2007 and 2012. Starting dose of bexarotene was 300 mg/m per day. The analysis included 3 patients with early-stage mycosis fungoides (MF), 16 patients with advanced-stage MF, and 2 patients with Sézary syndrome (SS). The mean duration of therapy with bexarotene was 14.5 months. Use of bexarotene resulted in an overall response rate of 81.0%, although the overall mortality rate was 52.8%. In our study, early-stage CTCL responded better than advanced-stage CTCL (100.0% vs. 77.8%, respectively). The mean time to observable response was 1.8 months, and the mean duration of the response was 16.4 months. Most significant side effects were hyperlipidemia, hypothyroidism, and a bleeding gastric ulcer. Based on the results of our analysis, bexarotene is a valuable tool in the treatment of refractory early-stage CTCL. Although a majority of patients initially responded to therapy, the high mortality rate in the advanced-stage group suggests that bexarotene does not completely resolve the therapeutic problems in all stages of CTCL. Patient stratification for bexarotene treatment may need a thorough reassessment, in that bexarotene may not be an effective drug in the very advanced stages of CTCL.
Vorinostat: A novel therapy for the treatment of cutaneous T-cell lymphoma. [2022]The pharmacology, pharmacokinetics, clinical efficacy, safety, adverse effects, dosage and administration, and role in therapy of vorinostat in the treatment of cutaneous T-cell lymphoma (CTCL) are reviewed.
The role of phototherapy in cutaneous T-cell lymphoma. [2010]Cutaneous T-cell lymphoma (CTCL) is a type of non-Hodgkin's lymphoma characterized by the malignant proliferation of T lymphocytes in the skin. Phototherapy has been proven an effective treatment modality for CTCL, in particular early stage disease (patch and plaque). Specifically, broadband ultraviolet B (BB-UVB), psoralen and ultraviolet A (PUVA), and more recently narrowband UVB (NB-UVB) are the skin-directed phototherapies typically utilized. Phototherapy poses the risk of sunburn, photoaging and photocarcinogenesis. Combination therapies with IFN-alpha, retinoids (acitretin and isotretinoin) and rexinoid (bexarotene) are adjunctive systemic therapies that facilitate enhanced therapeutic response and often allow for lower doses of phototherapy. Extracorporeal photopheresis (ECP) has also been shown to be effective in more advanced stage disease.
[Treatment of mycosis fungoides and Sézary syndrome]. [2022]Adequate therapeutic management of cutaneous T-cell lymphoma (CTCL) requires the identification of the exact CTCL stage and entity within the current WHO classification. There is no curative therapy for CTCL yet, so that treatment currently aims at improving symptoms and quality of life as well as reducing relapse rates. The treatment has to be stage-adapted. Therapeutic options comprise skin-directed as well as systemic treatment. In early stages, phototherapy and local steroids are the first-line therapeutic options. For the therapy of higher stages, interferon alpha and the RXR-specific retinoid bexarotene are used as first-line medications. Second-line treatment comprises monochemotherapy with agents like gemcitabine or liposomal doxorubicine. Nevertheless, the high relapse rates in higher stages make novel alternative treatment options necessary. As future therapy, especially the fusion protein brentuximab-vedotin directed against CD30 shows promising potential in clinical studies.