Study of Pegylated Interferon-Alfa 2b in Combination With PUVA Therapy In CTCL

Lymphoma Clinical Trial

Official title:

Pilot Study of Pegylated Interferon-Alfa 2b in Combination With PUVA Therapy in Cutaneous T-Cell Lymphoma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00724061
• Other study ID #: NU 07H4
• Secondary ID: P30CA060553NU 07
• Status: Terminated
• Phase: N/A
• Start date: September 2008
• Est. completion date: December 2011

Study information

• Verified date: November 2013
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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).

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: December 2011
• Est. primary completion date: June 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 120 Years

Eligibility

DISEASE CHARACTERISTICS:

• Histologically confirmed mycosis fungoides/Sezary syndrome

• Stage IB-IVA disease

• Erythrodermic disease allowed

• Measurable disease

• One or more indicatory lesions must be designated prior to study entry

PATIENT CHARACTERISTICS:

• ECOG/WHO performance status 0-1

• Life expectancy = 3 months

• Absolute neutrophil count = 1,500/mm³

• Platelet count = 75,000/mm³

• WBC = 3,000/mm³

• Serum creatinine = 2.0 mg/dL

• Total serum bilirubin = 2.2 mg/dL

• Serum AST and ALT = 2 times upper limit of normal

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• Patients must be disease free of prior malignancies for = 5 years except currently treated squamous cell or basal cell carcinoma of the skin, carcinoma in situ of the cervix, or surgically removed melanoma in situ of the skin (stage 0), with histologically confirmed free margins of excision

• No history of seizure disorder or severe heart disease

• No acute infections

• Diagnosed depression allowed with receiving appropriate care for depression

PRIOR CONCURRENT THERAPY:

• No prior psoralens with ultraviolet light A or interferon alfa therapy

• More than 4 weeks since prior topical therapy, systemic chemotherapy, or biologic therapy

• More than 4 weeks since prior surgery and fully recovered

• At least 1 week since prior antibiotics

• No other concurrent standard or investigational topical and systemic antipsoriatic or anticancer therapies including radiation, steroids, retinoids, nitrogen mustard, thalidomide, or other investigational agents

• No concurrent topical agents except emollients

Related Conditions & MeSH terms

• Lymphoma

Intervention

Biological:
• Pegylated interferon a-2b
PEG-IFN-a-2b will be administered subcutaneously once a week. The starting dose of PEG-IFN-a-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:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Activation Status of Key Signaling Molecules Between Baseline and After 2 Weeks of Treatment	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.	At baseline and after 2 weeks of treatment (for those patients who consented to this portion)
Other	Correlation of Response With Infiltration of Skin Lesions With Dendritic Cells, Cytotoxic CD8+ T-cells, and NK-cells		Baseline, 24 hours post-1st dose in the dose escalation phase, and 24 hours post-1st dose in the maintenance therapy phase
Primary	Number of Dose Limiting Toxicities (DLTs) Observed During Dose Escalation of PEG-IFN-a-2b	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.	From the date that the first patient began treatment until the last patient completed the dose escalation phase (up to 12 weeks per patient)
Primary	Change in Total Health-related Quality of Life Score Using the Functional Assessment of Cancer Therapy - Biologic Response Modifier (FACT-BRM)	The FACT-BRM is a patient self-report tool to assess health-related quality of life measures.	During 12 weeks of dose escalation and then up to one year during maintenance therapy.
Secondary	Number of Patients Exhibiting a Complete Response	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.	During 12 weeks of dose escalation and then up to one year during maintenance therapy.
Secondary	To Evaluate the Duration of Response	To evaluate duration of response related to combined pegylated IFN-a-2b plus PUVA or NB-UVB therapy.	At each study visit