Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information
Registry Information

Alternate Title

Interleukin-12 and Interleukin-2 in Treating Patients With Mycosis Fungoides

Basic Trial Information

Phase Type Status Age Sponsor Protocol IDs Phase II, Phase I Treatment Completed 18 and over NCI UPCC-10401 NCI-1831, 1831, NCT00052377

Objectives

1. Determine the response rate (complete and partial) in patients with mycosis fungoides treated with interleukin-12 (IL-12).
2. Determine the frequency of refractory disease in patients treated with this drug.
3. Determine the toxic effects of this drug in these patients.
4. 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.
5. Determine the maximum tolerated dose and recommended dose of IL-2 when administered with IL-12 in these patients.
6. Determine immune and cytokine response over time in patients treated with this regimen.
7. Determine the frequency of improved clinical response in patients treated with this regimen.
8. 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.

Entry Criteria

Disease Characteristics:

• Histologically confirmed mycosis fungoides
  • Stage Ib-IV



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



• No CNS disease

Prior/Concurrent Therapy:

Biologic therapy

• 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

Chemotherapy

• 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

Endocrine therapy

• 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

Radiotherapy

• No concurrent radiotherapy

Surgery

• Not specified

Other

• 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

Patient Characteristics:

Age

• 18 and over

Performance status

• Karnofsky 70-100%

Life expectancy

• At least 6 months

Hematopoietic

• WBC ≥ 3,000/mm³ but ≤ 40,000/mm³
• Absolute neutrophil count ≥ 1,500/mm³
• Platelet count ≥ 100,000/mm³
• Hemoglobin ≥ 10 g/dL (transfusion or epoetin alfa allowed)

Hepatic

• Bilirubin ≤ 1.5 times upper limit of normal (ULN)
• AST and ALT ≤ 2 times ULN

Renal

• Creatinine ≤ 1.5 times ULN
• Creatinine clearance ≥ 60 mL/min

Cardiovascular

• EKG normal
• No known cardiac and peripheral vascular disease
• No cardiac arrhythmias requiring medical treatment

Pulmonary

• Chest x-ray normal

Immunologic

• 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

Gastrointestinal

• No clinically significant gastrointestinal bleeding
• No uncontrolled peptic ulcer disease
• No history of inflammatory bowel disease

Other

• 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

Expected Enrollment

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

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.

Trial Contact Information

Trial Lead Organizations

Abramson Cancer Center of the University of Pennsylvania

Alain Rook, MD, Protocol chair		Ph: 215-662-7610 Email: arook@mail.med.upenn.edu

Registry Information
Official Title		A Phase II Open-Label Study Of Recombinant Human Interleukin-12 (NSC 672423) In Mycosis Fungoides (MF) Patients With Cross-Over To Phase I Evaluation Of Escalating Doses Of Interleukin-2 (NSC 373364) Administered With Interleukin-12
Trial Start Date		2002-10-01
Registered in ClinicalTrials.gov		NCT00052377
Date Submitted to PDQ		2002-09-27
Information Last Verified		2005-02-24
NCI Grant/Contract Number		CA89442, CA16520

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