Study of Pegylated Interferon-Alfa 2b in Combination With PUVA Therapy In CTCL
Study Details
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).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
N/A |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 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 Names:
Other: 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 Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Dose Limiting Toxicities (DLTs) Observed During Dose Escalation of PEG-IFN-α-2b [From the date that the first patient began treatment until the last patient completed the dose escalation phase (up to 12 weeks per patient)]
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) [During 12 weeks of dose escalation and then up to one year during maintenance therapy.]
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 [During 12 weeks of dose escalation and then up to one year during maintenance therapy.]
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 [At each study visit]
To evaluate duration of response related to combined pegylated IFN-α-2b plus PUVA or NB-UVB therapy.
Other Outcome Measures
- Change in Activation Status of Key Signaling Molecules Between Baseline and After 2 Weeks of Treatment [At baseline and after 2 weeks of treatment (for those patients who consented to this portion)]
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 [Baseline, 24 hours post-1st dose in the dose escalation phase, and 24 hours post-1st dose in the maintenance therapy phase]
Eligibility Criteria
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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Robert H. Lurie Comprehensive Cancer Center at Northwestern University | Chicago | Illinois | United States | 60611-3013 |
Sponsors and Collaborators
- Northwestern University
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: Timothy M. Kuzel, MD, Robert H. Lurie Cancer Center
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- NU 07H4
- P30CA060553
- NU 07H4
- SPRI-NU-07H4
- STU00002993
Study Results
Participant Flow
| Recruitment Details | Study opened at Northwestern University in 09/2008 with an accrual goal of 15 subjects. The study was suspended from 11/2009 to 07/2010 due to a shortage of psoralens; a revision allowed the use of PUVA or NB-UVB for UV therapy. A total of 7 patients were enrolled before the study was closed due to poor accrual in 05/2012. |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | PEG-IFN-alpha-2b + UV Therapy |
|---|---|
| Arm/Group Description | Pegylated interferon α-2b in combination with UV therapy (either PUVA or NB-UVB). |
| Period Title: Dose Escalation Phase | |
| STARTED | 7 |
| COMPLETED | 2 |
| NOT COMPLETED | 5 |
| Period Title: Dose Escalation Phase | |
| STARTED | 2 |
| COMPLETED | 2 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | PEG-IFN-alpha-2b + UV Therapy |
|---|---|
| Arm/Group Description | Pegylated interferon α-2b in combination with UV therapy (either PUVA or NB-UVB). |
| Overall Participants | 7 |
| Age, Customized (participants) [Number] | |
| 30-39 |
1
14.3%
|
| 40-49 |
2
28.6%
|
| 50-59 |
2
28.6%
|
| 60-69 |
0
0%
|
| 70-79 |
2
28.6%
|
| 80-89 |
0
0%
|
| Sex: Female, Male (Count of Participants) | |
| Female |
3
42.9%
|
| Male |
4
57.1%
|
| Region of Enrollment (participants) [Number] | |
| United States |
7
100%
|
Outcome Measures
| Title | Number of Dose Limiting Toxicities (DLTs) Observed During Dose Escalation of PEG-IFN-α-2b |
|---|---|
| Description | 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. |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | PEG-IFN-alpha-2b + UV Therapy |
|---|---|
| Arm/Group Description | Pegylated interferon α-2b in combination with UV therapy (either PUVA or NB-UVB). |
| Measure Participants | 7 |
| Number [dose limiting toxicities] |
0
|
| 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| No data collected for this outcome measure. |
| Arm/Group Title | PEG-IFN-alpha-2b + UV Therapy |
|---|---|
| Arm/Group Description | Pegylated interferon α-2b in combination with UV therapy (either PUVA or NB-UVB). |
| Measure Participants | 0 |
| Title | Number of Patients Exhibiting a Complete Response |
|---|---|
| Description | 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. |
| Time Frame | During 12 weeks of dose escalation and then up to one year during maintenance therapy. |
Outcome Measure Data
| Analysis Population Description |
|---|
| No data collected for this outcome measure. |
| Arm/Group Title | PEG-IFN-alpha-2b + UV Therapy |
|---|---|
| Arm/Group Description | Pegylated interferon α-2b in combination with UV therapy (either PUVA or NB-UVB). |
| Measure Participants | 0 |
| 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| No data collected for this outcome measure. |
| Arm/Group Title | PEG-IFN-alpha-2b + UV Therapy |
|---|---|
| Arm/Group Description | Pegylated interferon α-2b in combination with UV therapy (either PUVA or NB-UVB). |
| Measure Participants | 0 |
| 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) |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
| Title | Correlation of Response With Infiltration of Skin Lesions With Dendritic Cells, Cytotoxic CD8+ T-cells, and NK-cells |
|---|---|
| Description | |
| Time Frame | Baseline, 24 hours post-1st dose in the dose escalation phase, and 24 hours post-1st dose in the maintenance therapy phase |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title |
|---|
| Arm/Group Description |
Adverse Events
| Time Frame | Adverse events were reported from the date the first patient began treatment until 30 days after the last patient went off study treatment. | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | PEG-IFN-alpha-2b + UV Therapy | |
| Arm/Group Description | Pegylated interferon α-2b in combination with UV therapy (either PUVA or NB-UVB). | |
All Cause Mortality |
||
| PEG-IFN-alpha-2b + UV Therapy | ||
| Affected / at Risk (%) | # Events | |
| Total | / (NaN) | |
Serious Adverse Events |
||
| PEG-IFN-alpha-2b + UV Therapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 2/7 (28.6%) | |
| Cardiac disorders | ||
| Ventricular arrhythmia - ventricular tachycardia | 1/7 (14.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Injection site reaction/extravasation changes | 1/7 (14.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||
| PEG-IFN-alpha-2b + UV Therapy | ||
| Affected / at Risk (%) | # Events | |
| Total | 7/7 (100%) | |
| Blood and lymphatic system disorders | ||
| Hemoglobin (decrease) | 4/7 (57.1%) | 5 |
| Leukocytes (total WBC) - decreased | 5/7 (71.4%) | 8 |
| Lymphopenia | 5/7 (71.4%) | 6 |
| Neutrophils/granulocytes (ANC/AGC) - decreased | 3/7 (42.9%) | 7 |
| Other impact on blood/bone marrow | 2/7 (28.6%) | 2 |
| Platelets (decreased) | 3/7 (42.9%) | 6 |
| Gastrointestinal disorders | ||
| Anorexia | 1/7 (14.3%) | 1 |
| Diarrhea | 2/7 (28.6%) | 2 |
| Nausea | 2/7 (28.6%) | 2 |
| General disorders | ||
| Constitutional symptoms - other (fever, chills, sweats, aches & pains) | 2/7 (28.6%) | 3 |
| Fatigue | 6/7 (85.7%) | 7 |
| Fever | 1/7 (14.3%) | 1 |
| Insomnia | 1/7 (14.3%) | 2 |
| Odor (patient) | 1/7 (14.3%) | 1 |
| Pain - head/headache | 3/7 (42.9%) | 4 |
| Rigors/chills | 1/7 (14.3%) | 1 |
| Weight loss - intervention not indicated | 3/7 (42.9%) | 3 |
| Metabolism and nutrition disorders | ||
| ALT, SGPT elevation | 4/7 (57.1%) | 5 |
| AST, SGOT elevation | 5/7 (71.4%) | 6 |
| Albumin, serum-low (hypoalbuminemia) | 3/7 (42.9%) | 7 |
| Calcium, serum-low (hypocalcemia) | 1/7 (14.3%) | 1 |
| Creatinine - elevation | 1/7 (14.3%) | 1 |
| Glucose, serum-high (hyperglycemia) | 5/7 (71.4%) | 7 |
| Potassium, serum-high (hyperkalemia) | 1/7 (14.3%) | 1 |
| Musculoskeletal and connective tissue disorders | ||
| Musculoskeletal/soft tissue - other (injection site pain) | 1/7 (14.3%) | 1 |
| Pain - muskuloskeletal | 2/7 (28.6%) | 3 |
| Respiratory, thoracic and mediastinal disorders | ||
| Cough | 1/7 (14.3%) | 1 |
| Dyspnea (shortness of breath) | 1/7 (14.3%) | 1 |
| Skin and subcutaneous tissue disorders | ||
| Burn | 1/7 (14.3%) | 2 |
| Hypopigmentation - slight or localized | 1/7 (14.3%) | 1 |
| Infection - skin (cellulitis) | 1/7 (14.3%) | 2 |
| Pruritus/itching - mild or localized | 4/7 (57.1%) | 4 |
| Rash/desquamation | 1/7 (14.3%) | 1 |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Dr. Timothy Kuzel |
|---|---|
| Organization | Northwestern University |
| Phone | 312-695-6180 |
| cancertrials@northwestern.edu |
- NU 07H4
- P30CA060553
- NU 07H4
- SPRI-NU-07H4
- STU00002993