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

Primary Purpose

Lymphoma

Status

Terminated

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Pegylated interferon α-2b

Psoralens with ultraviolet light A

Narrowband-ultraviolet light B

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring recurrent mycosis fungoides/Sezary syndrome, stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, recurrent cutaneous T-cell non-Hodgkin lymphoma, stage I cutaneous T-cell non-Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

PEG-IFN-α-2b + UV therapy

Arm Description

Pegylated interferon α-2b in combination with UV therapy (either PUVA or NB-UVB).

Outcomes

Primary Outcome Measures

Number of Dose Limiting Toxicities (DLTs) Observed During Dose Escalation of PEG-IFN-α-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.

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.

Secondary Outcome Measures

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.

To Evaluate the Duration of Response

To evaluate duration of response related to combined pegylated IFN-α-2b plus PUVA or NB-UVB therapy.

Full Information

NCT ID

NCT00724061

First Posted

July 26, 2008

Last Updated

November 20, 2018

Sponsor

Northwestern University

Collaborators

National Cancer Institute (NCI)

1. Study Identification

Unique Protocol Identification Number

NCT00724061

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

November 2013

Overall Recruitment Status

Terminated

Why Stopped

Closed early due to poor accrual.

Study Start Date

September 2008 (undefined)

Primary Completion Date

June 2011 (Actual)

Study Completion Date

December 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Northwestern University

Collaborators

National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief 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).

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Lymphoma

Keywords

recurrent mycosis fungoides/Sezary syndrome, stage I mycosis fungoides/Sezary syndrome, stage II mycosis fungoides/Sezary syndrome, stage III mycosis fungoides/Sezary syndrome, stage IV mycosis fungoides/Sezary syndrome, recurrent cutaneous T-cell non-Hodgkin lymphoma, stage I cutaneous T-cell non-Hodgkin lymphoma, stage II cutaneous T-cell non-Hodgkin lymphoma, stage III cutaneous T-cell non-Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

7 (Actual)

8. Arms, Groups, and Interventions

Arm Title

PEG-IFN-α-2b + UV therapy

Arm Type

Experimental

Arm Description

Pegylated interferon α-2b in combination with UV therapy (either PUVA or NB-UVB).

Intervention Type

Biological

Intervention Name(s)

Pegylated interferon α-2b

Other Intervention Name(s)

PEG-Interferon alfa-2b, PEG-IFN-α-2b, PEG-Intron

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Psoralens with ultraviolet light A

Other Intervention Name(s)

PUVA

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Narrowband-ultraviolet light B

Other Intervention Name(s)

NB-UVB

Intervention Description

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.

Primary Outcome Measure Information:

Title

Number of Dose Limiting Toxicities (DLTs) Observed During Dose Escalation of PEG-IFN-α-2b

Description

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)

Title

Change in Total Health-related Quality of Life Score Using the Functional Assessment of Cancer Therapy - Biologic Response Modifier (FACT-BRM)

Description

The FACT-BRM is a patient self-report tool to assess health-related quality of life measures.

Time Frame

During 12 weeks of dose escalation and then up to one year during maintenance therapy.

Secondary Outcome Measure Information:

Title

Number of Patients Exhibiting a Complete Response

Description

Time Frame

During 12 weeks of dose escalation and then up to one year during maintenance therapy.

Title

To Evaluate the Duration of Response

Description

To evaluate duration of response related to combined pegylated IFN-α-2b plus PUVA or NB-UVB therapy.

Time Frame

At each study visit

Other Pre-specified Outcome Measures:

Title

Change in Activation Status of Key Signaling Molecules Between Baseline and After 2 Weeks of Treatment

Description

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.

Time Frame

At baseline and after 2 weeks of treatment (for those patients who consented to this portion)

Title

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

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

120 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Timothy M. Kuzel, MD

Organizational Affiliation

Robert H. Lurie Cancer Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

Robert H. Lurie Comprehensive Cancer Center at Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611-3013

Country

United States

12. IPD Sharing Statement

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

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