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Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00052377
Other study ID # NCI-2012-02504
Secondary ID 10401R01CA089442
Status Terminated
Phase Phase 1/Phase 2
First received January 24, 2003
Last updated January 15, 2013
Start date September 2002

Study information

Verified date January 2013
Source National Cancer Institute (NCI)
Contact n/a
Is FDA regulated No
Health authority United States: Food and Drug Administration
Study type Interventional

Clinical Trial Summary

Phase I/II trial to study the effectiveness of combining interleukin-12 with interleukin-2 in treating patients who have mycosis fungoides. Biological therapies, such as interleukin-12 and interleukin-2, use different ways to stimulate the immune system and stop cancer cells from growing. Combining more than one biological therapy may kill more tumor cells


Description:

OBJECTIVES:

I. Determine the response rate (complete and partial) in patients with mycosis fungoides treated with interleukin-12 (IL-12).

II. Determine the frequency of refractory disease in patients treated with this drug.

III. Determine the toxic effects of this drug in these patients. IV. Determine the feasibility and dose-limiting toxic effects (DLT) of interleukin-2 (IL-2) when administered with IL-12 in patients who have not shown disease progression after 12 weeks of IL-12 and in those who have shown disease progression after 12 weeks of IL-12.

V. Determine the maximum tolerated dose and recommended dose of IL-2 when administered with IL-12 in these patients.

VI. Determine immune and cytokine response over time in patients treated with this regimen.

VII. Determine the frequency of improved clinical response in patients treated with this regimen.

VIII. Determine the biologic correlates of response, including levels of interferon gamma production, natural killer cell activity, infiltration of skin lesions by CD8-positive cells, lymphocyte IL-12 receptor expression, signal transducers and activators of transcription protein levels and IL-12 signal transduction, and induction of apoptosis in tumor cells in the skin of patients treated with this regimen.

OUTLINE: This is an open-label, multicenter, dose-escalation study of interleukin-2 (IL-2).

Patients receive interleukin-12 (IL-12) subcutaneously (SC) twice weekly for 24 weeks.

Disease is assessed at 13 weeks. Patients who do not have progressive disease also receive IL-2 SC 3 consecutive days a week during weeks 13-24. Patients with progressive disease at week 13 receive IL-2 SC at a fixed dose during weeks 13-24.

Patients with responding disease after week 24 may continue to receive IL-2 and IL-12 for another 12 weeks.

Cohorts of 3-6 patients receive escalating doses of IL-2 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The recommended dose (RD) is the dose preceding the MTD. Additional patients are treated at the RD.

Patients are followed at 6 months.

PROJECTED ACCRUAL: A total of 18-46 patients will be accrued for this study within 28 months.


Recruitment information / eligibility

Status Terminated
Enrollment 46
Est. completion date
Est. primary completion date June 2005
Accepts healthy volunteers No
Gender Both
Age group 18 Years and older
Eligibility Inclusion Criteria:

- Histologically confirmed mycosis fungoides

- Stage Ib-IV

- At least 5% of total blood mononuclear cells must be CD8-positive lymphocytes

- No CNS disease

- Performance status - Karnofsky 70-100%

- At least 6 months

- WBC = 3,000/mm^3 but = 40,000/mm^3

- Absolute neutrophil count = 1,500/mm^3

- Platelet count = 100,000/mm^3

- Hemoglobin = 10 g/dL (transfusion or epoetin alfa allowed)

- Bilirubin = 1.5 times upper limit of normal (ULN)

- AST and ALT = 2 times ULN

- Creatinine = 1.5 times ULN

- Creatinine clearance = 60 mL/min

- EKG normal

- No known cardiac and peripheral vascular disease

- No cardiac arrhythmias requiring medical treatment

- Chest x-ray normal

- No history of or clinically significant autoimmune disease (e.g., rheumatoid arthritis), autoimmune hemolytic anemia, or positive Coombs' test

- No HTLV-I or HTLV-II-associated disease

- HIV negative

- Antinuclear antibody negative

- Rheumatoid factor negative

- No serious concurrent infection requiring IV antibiotics

- No clinically significant gastrointestinal bleeding

- No uncontrolled peptic ulcer disease

- No history of inflammatory bowel disease

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- No history of peripheral neuropathy

- No other major illness that would substantially increase the patient's risk

- Prior interferon allowed

- Prior denileukin diftitox allowed

- No prior interleukin (IL)-2 or IL-12

- No prior anti-T-cell monoclonal antibody therapy

- No other concurrent biologic therapy

- Prior topical imidazole mustard or carmustine allowed

- Prior bexarotene allowed

- Prior oral methotrexate allowed

- At least 3 weeks since prior topical chemotherapy

- At least 8 weeks since prior treatment with any single chemotherapeutic agent (12 weeks for multiple chemotherapeutic agents)

- Treatment must not have included steroids

- No prior systemic chemotherapy

- No prior fludarabine, pentostatin, or cladribine

- No concurrent systemic chemotherapy

- At least 3 weeks since prior topical or systemic steroids more potent than 1% hydrocortisone

- No concurrent systemic corticosteroids

- No concurrent low-potency steroid creams

- No concurrent radiotherapy

- Not specified

- At least 3 weeks since prior psoralen-ultraviolet-light (PUVA) or ultraviolet B (UVB)

- At least 3 weeks since prior retinoids

- At least 3 weeks since prior investigational drugs

- Prior photopheresis allowed

- No other concurrent investigational therapy

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Biological:
aldesleukin
Given SC
recombinant interleukin-12
Given SC
Other:
laboratory biomarker analysis
Correlative studies

Locations

Country Name City State
United States Abramson Cancer Center of The University of Pennsylvania Philadelphia Pennsylvania

Sponsors (1)

Lead Sponsor Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Clinical response rate defined as the percentage of patients who achieve complete or partial response (Phase I) Up to week 13 No
Primary Refractory disease defined as a patient who initially shows clinical improvement in the early weeks of treatment and then exhibits a response plateau for >= 30 days or exhibits progression of their disease (Phase I) Logistic regression may be employed to explore the relationships between clinical response or refractory disease and baseline patient features. Up to week 13 No
Primary Improved clinical response defined as a patient who had refractory or persistent disease and who subsequently had a >= 25% clinical improvement for >= 30 days during aldesleukin and recombinant interleukin-12 therapy (Phase II) Up to week 25 No
Primary Toxicities graded using National Cancer Institute (NCI) Common Toxicity Criteria Version 2.0 (Phase I) Up to 6 months Yes
Secondary Dose-limiting toxicity (DLT) is defined as any grade 3 or higher hematologic or non-hematologic toxicity (Phase II) Up to week 25 Yes
Secondary Maximum tolerated dose (MTD), defined as the dose level at which at least 2 of 3 patients or at least 2 of 6 patients experience DLT, graded according to the NCI CTC v2.0 (Phase II) Up to week 25 Yes
Secondary Recommended dose (RD), defined as the dose level at which 0/6 or 1/6 patients experience DLT and at least 2 patients treated at a higher dose level experience DLT (Phase II) Up to week 25 Yes
Secondary Interferon gamma production Compared between the two groups by two independent samples t-test or nonparametric Mann-Whitney test, as appropriate. Up to week 25 No
Secondary Infiltration of skin lesions by CD8+ cells Up to week 25 No
Secondary Induction of apoptosis in infiltrating tumor cells in the skin Up to week 26 No
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