Study of Pegylated Interferon-Alfa 2b in Combination With PUVA Therapy In CTCL
RATIONALE: PEG-interferon alfa-2b may interfere with the growth of cancer cells and slow the growth of mycosis fungoides/Sezary syndrome. Ultraviolet light therapy uses a drug, such as psoralen, that is absorbed by cancer cells. The drug becomes active when it is exposed to ultraviolet light. When the drug is active, cancer cells are killed. Giving PEG-interferon alfa-2b together with ultraviolet light therapy may kill more cancer cell.
PURPOSE: This is a pilot study of dose-escalating pegylated IFN-α-2b and PUVA or NB-UVB. The purpose is to study the side effects and best dose of PEG-interferon alfa-2b to be given together with ultraviolet light therapy in patients with stage IB, stage II, stage III, or stage IVA mycosis fungoides/Sezary syndrome (CTCL).
Biological: Pegylated interferon α-2b
Other: Psoralens with ultraviolet light A
Other: Narrowband-ultraviolet light B
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Pilot Study of Pegylated Interferon-Alfa 2b in Combination With PUVA Therapy in Cutaneous T-Cell Lymphoma|
- Number of Dose Limiting Toxicities (DLTs) Observed During Dose Escalation of PEG-IFN-α-2b [ Time Frame: From the date that the first patient began treatment until the last patient completed the dose escalation phase (up to 12 weeks per patient) ] [ Designated as safety issue: Yes ]
Adverse events are graded according to the National Cancer Institute's Common Toxicity Criteria (CTCAE) version 3.0. In general, grades are assigned as follows:
Grade 1 Mild AE Grade 2 Moderate AE Grade 3 Severe AE Grade 4 Life-threatening or disabling AE Grade 5 Death related to AE
A dose limiting toxicity (DLT) will be defined as any grade 3 or higher hematologic toxicity or any grade 4 non-hematologic toxicity.
- Change in Total Health-related Quality of Life Score Using the Functional Assessment of Cancer Therapy - Biologic Response Modifier (FACT-BRM) [ Time Frame: From the date that the first patient was registerd until the last patient came off treatment (score assessed at baseline, every 2 weeks during dose escalation, and then monthly during maintenance therapy for each patient) ] [ Designated as safety issue: No ]The FACT-BRM is a patient self-report tool to assess health-related quality of life measures.
- Number of Patients Exhibiting a Complete Response [ Time Frame: From the date the first patient begins treatement until the last patient achieves complete response (response was assessed every 4 weeks) ] [ Designated as safety issue: No ]
Response was assessed according to the Composite Assessment of Index Lesion Disease Severity. Clinical signs are graded on scales of 0 to 8 (0 being no evidence of disease and 8 being the near worst severity of sign/symptom). The CA response is calculated as the ratio of the sum of the grades for all clinical signs plus the surface areas for all index lesions at each visit compared to the sum of these grades at baseline. The CA also considers all other cutaneous lesions and any extra-cutaneous manifestations of disease.
CR requires a CA ratio of 0 (zero) with no evidence of new disease (abnormal or pathologically positive lymph nodes, cutaneous or other tumor manifestations, visceral disease) present over 4 weeks. Patients with Sézary Syndrome must have no evidence of circulating Sézary cells (< 5% Sézary cells are considered to be not significant). Skin biopsy is required for documentation of CR.
- To Evaluate the Duration of Response [ Time Frame: At each study visit ] [ Designated as safety issue: Yes ]To evaluate duration of response related to combined pegylated IFN-α-2b plus PUVA or NB-UVB therapy.
- Change in Activation Status of Key Signaling Molecules Between Baseline and After 2 Weeks of Treatment [ Time Frame: At baseline and after 2 weeks of treatment (for those patients who consented to this portion) ] [ Designated as safety issue: No ]The activation status of key signaling molecules affecting the PI3K and JAK/STAT pathways was to be analyzed in samples of skin and blood taken at baseline and after 2 weeks of treatment. Participation in this exploratory component of the trial was optional for patients.
- Correlation of Response With Infiltration of Skin Lesions With Dendritic Cells, Cytotoxic CD8+ T-cells, and NK-cells [ Time Frame: Baseline, 24 hours post-1st dose in the dose escalation phase, and 24 hours post-1st dose in the maintenance therapy phase ] [ Designated as safety issue: No ]
|Study Start Date:||September 2008|
|Study Completion Date:||December 2011|
|Primary Completion Date:||June 2011 (Final data collection date for primary outcome measure)|
Experimental: PEG-IFN-α-2b + UV therapy
Pegylated interferon α-2b in combination with UV therapy (either PUVA or NB-UVB).
Biological: Pegylated interferon α-2b
PEG-IFN-α-2b will be administered subcutaneously once a week. The starting dose of PEG-IFN-α-2b will be 1.5μg/kg. Each patient will undergo dose escalation to 3, 4.5, 6, 7.5, and up to 9μg/kg every 2 weeks or to maximum tolerated dose will be allowed. If no dose limiting toxicity (DLT) is observed, the maximum dose reached will be expanded. Once this dose has been given weekly for 2 weeks with no DLT, therapy will continue at this dose for up to 1 year depending on response.
Other Names:Other: Psoralens with ultraviolet light A
Oral psoralen (8-methoxypsoralen, 0.6-1.0 mg/kg) will be taken 1.5 to 2 hours prior to UVA treatment. The initial UVA dosage will be approximately 0.5 to 1.5 J/cm2, and will be increased in increments as determined by skin type and tolerability. PUVA therapy will be given 2-3 times per week until complete remission (CR) is achieved. Afterwards, additional maintenance therapy will be given with a gradual reduction from once a week to every 4-6 weeks up to 1 year after CR was achieved.
Other Name: PUVAOther: Narrowband-ultraviolet light B
The initial NB-UVB dose will be 70% of the patient's MED and approximately 0.2 J/cm2 and will be increased by 15% of each subsequent treatment as determined by skin type and/or tolerability. Therapy will be given 3 times per week until complete remission (CR) is achieved. Additional maintenance therapy will be administered while gradually reducing NB-UVB from thrice weekly to once a week. All patients will continue maintenance NB-UVB therapy until 1 year after they have achieved CR.
Other Name: NB-UVB
Patients receive PEG-interferon alfa-2b subcutaneously once weekly for 12 months in the absence of disease progression or unacceptable toxicity. Patients also receive UV light therapy (either PUVA or NB-UVB).
Health-related quality of life is assessed periodically using the FACT-BRM, FACT-G, and FACT-CTCL questionnaires.
After completion of study therapy, patients are followed for 1 year.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00724061
|United States, Illinois|
|Robert H. Lurie Comprehensive Cancer Center at Northwestern University|
|Chicago, Illinois, United States, 60611-3013|
|Principal Investigator:||Timothy M. Kuzel, MD||Robert H. Lurie Cancer Center|