A Phase I/IIa, Dose-Ranging Safety and Efficacy Study of Topical Resiquimod for the Treatment of Early Stage Cutaneous T Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 13
- 试验地点
- 1
- 主要终点
- The Number of Participants That Tolerated the Maximum Drug Dose
研究概览
简要总结
The objective of this study is to explore the safety and the preliminary efficacy of two concentrations (0.06% and 0.03%)gel that is applied to lesions of early stage (IA, IB,IIA) Cutaneous T Cell Lymphoma patients.
This study is supported by grant 1R01FD004092-01A1 from the Office of Orphan Products Development, FDA.
详细描述
This is an open-label, dose-ranging study in subjects with early stage (IA, IB, 2A) CTCL. Patients with early stage CTCL will be screened for eligibility. Eligible subjects will be enrolled in up to 2 treatment groups of up to 8 subjects each.
Treatment groups will be:
- Resiquimod 0.06% will be applied in dosing frequencies that are periodically adjusted according to tolerability. Subjects will begin dosing at 3 times per week (3x/wk), and will be evaluated at the clinic every two weeks. The dosing frequency (1, 2, 3, 5, or 7x/wk) may be adjusted in a stepwise manner after each two week interval based on the physician assessment of tolerability (maintained, increased, decreased with or without a dosing interruption [rest period]). Resiquimod will be applied for 8 weeks (COT1) followed by a 4 week no-treatment period. If the subject has not required permanent discontinuation from treatment, the subject will repeat a second course of treatment of 8 weeks (COT2) followed by a 4 week no-treatment period. Subjects will apply up to 500 mg of study drug per day based upon the total surface area that is treated (~250 mg of product / 50 cm2 of lesion surface area).
- Resiquimod 0.03% applied as described for Treatment Group 1. However, initial applications will be 5 times per week with the dosing frequency adjusted upward as tolerated every two weeks.
The initial cohort will be assigned to Treatment Group 1. After 4 subjects have completed at least 4 weeks of dosing, a safety review meeting will be conducted by a committee consisting of the P.I., a biostatistician, and at least one other physician familiar with CTCL responses. The Safety Review Committee (SRC) will determine, based on the review of the tolerability data, the starting concentration/frequency of the next group of 4 subjects.
For a given subject the concentration assignment (0.06% or 0.03%) will remain the same (only frequency may vary). It is planned that approximately 8 subjects will be enrolled in each group.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Males or female ≥18 years of age at the time of study enrollment
- •Have a clinical diagnosis of cutaneous T cell lymphoma CTCL, including documentation of a skin biopsy with histological findings consistent with CTCL (atypical epidermotrophic or folliculocentric T-cells). Unconfirmed diagnosis of CTCL must have a biopsy to confirm at screening
- •Have Stage IA, IB or IIA: T1 or T2 (patches or plaques) with measurable lesions.
- •Previous treatment with at least one standard therapy used to treat Stage IA, IB or IIA CTCL including but not limited to oral corticosteroids, high-potency topical corticosteroids, topical mechlorethamine, topical bexarotene, PUVA, UVB, total body electron beam radiation, biological response or oral methotrexate.
- •Have measurable skin disease with at least 1 to 4 eligible baseline target lesions with a total area >25 cm2 but <100 cm
- •Eligible lesions must be below the neck and may not involve the genitalia, intertriginous areas, internally, or to frankly ulcerated or infected skin.
- •Generally healthy other than for CTCL, or with other stable diseases/conditions that are adequately controlled.
- •Willing and able to provide written informed consent.
- •Willing and able to adhere to the protocol requirements, including but not limited to study drug dosing, study drug visits, medication and treatment restrictions, and laboratory tests.
- •Willing and able to discontinue concomitant medications or treatments for CTCL during the study.
- •If a female of child bearing potential, willing to use adequate contraception (defined as double-method contraception, e.g. oral contraceptive usage by subject and condom by partner). Non-child bearing potential is defined as being at least 2 years post-menopausal or being surgically sterile.
- •Willing to abstain from therapeutic sunbathing, tanning beds, etc. for the duration of the study.
排除标准
- •Have a known allergy to resiquimod or any of the excipients in the study drug.
- •Stage IIB or greater CTCL.
- •Require immediate treatment for progressive CTCL.
- •Are unable to discontinue current treatment for CTCL due to risk of progression.
- •Within 8 weeks of treatment initiation (Day 0), have received treatment with:
- •Total body electron beam radiation
- •Investigational drugs or treatments
- •Within 4 weeks of treatment initiation (Day 0), have received treatment with:
- •Local radiation therapy
- •UVB therapy
- •Any topical chemotherapy
- •Photopheresis
- •Systemic retinoids, corticosteroids, immune response modifiers including imiquimod, interferon inducers, chemotherapeutic agents, biologic agents including interferon
- •Topical corticosteroids or retinoids
- •Within 2 weeks of treatment initiation (Day 0), have received at or adjacent to the target treatment lesions.
- •Any surgical procedures other than biopsies related to CTCL diagnosis or follow-up
- •Any topical treatment other than bland moisturizers (creams, lotions, emollients, etc).
- •Have other concurrent cutaneous conditions in the treatment area or immediately adjacent to the treatment area that would be exacerbated by resiquimod or interfere with assessments.
- •Have a grade 2 or greater laboratory abnormalities (CTCAE v4) at baseline for any of the following:
- •Hemoglobin
- •White blood cell count
- •Platelet count
- •Alanine transferase
- •Aspartate transferase
- •Creatinine
- •Have a known history of or a positive serologic test for infection with human immunodeficiency virus or human T lymphotrophic virus.
- •Are pregnant or nursing, or intending to become pregnant within the duration of the study.
- •Have any clinically significant medical conditions that are unstable, progressive, or inadequately controlled in the opinion of the investigator, that would pose a potential risk for the subject, result in poor compliance with the study requirements, or require treatment with an excluded medication or treatment during the study.
- •Have an active chemical or alcohol dependency as assessed by the investigator.
- •Have systemic collagen vascular disorder, systemic autoimmune disease, an organ transplant or diagnosis of cancer within 5 years other than CTCL (not including basal cell carcinoma, non-invasive squamous cell cancer of the skin, malignant melanoma in situ, or cervical carcinoma in situ).
研究组 & 干预措施
topical resiquimod 0.06%
Topical resiquimod 0.06% will be applied in dosing frequencies that are periodically adjusted to tolerability. Dosing frequency will be 3 times a week. The dosing frequency may be adjusted (1,2,3,5,or 7times per week) based on the physician assessment of tolerability. Treatment will occur for 8 weeks followed by 4 weeks rest followed by another 8 weeks of treatment with 4 weeks rest. At 24 weeks a final evaluation will be performed. Those with a partial response at week 24 will have the option to continue therapy for up to another 12 weeks.
干预措施: Topical resiquimod 0.06% (Drug)
topical resiquimod 0.03%
Topical resiquimod 0.03% will be applied in dosing frequencies that are periodically adjusted to tolerability. Dosing frequency will begin 5 times a week. The dosing frequency may be adjusted (1,2,3,5,or 7times per week) based on the physician assessment of tolerability. Treatment will occur for 8 weeks followed by 4 weeks rest followed by another 8 weeks of treatment with 4 weeks rest. At 24 weeks a final evaluation will be performed. Those with a partial response at week 24 will have the option to continue therapy for up to another 12 weeks.
干预措施: topical resiquimod 0.03% (Drug)
结局指标
主要结局
The Number of Participants That Tolerated the Maximum Drug Dose
时间窗: after 4 subjects have completed 4 weeks of study drug
After four subjects have completed at least four weeks of study drug dosing a safety review meeting will be conducted by a safety review committee. No subjects will be enrolled in the next concentration (0.03%)group until all eight have been evaluated in the 0.06% group. The safety review committee reviews all patient data including adverse events to indicate whether the patient can escalate to the highest dose.
次要结局
- Secondary End Points: Efficacy- SWAT SCORE(Up to 24 weeks or At the conclusion of patient therapy)
- Secondary End Points: Efficacy- CAILDS SCORE(Up to 24 weeks or At the conclusion of patient therapy)