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 Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Enrollment
- 46
- Locations
- 2
- Primary Endpoint
- Clinical response rate defined as the percentage of patients who achieve complete or partial response (Phase I)
Study Overview
Brief 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
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
- +6 more not shown
Exclusion Criteria
- Not provided
Outcomes
Primary Outcomes
Clinical response rate defined as the percentage of patients who achieve complete or partial response (Phase I)
Time Frame: Up to week 13
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)
Time Frame: Up to week 13
Logistic regression may be employed to explore the relationships between clinical response or refractory disease and baseline patient features.
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)
Time Frame: Up to week 25
Toxicities graded using National Cancer Institute (NCI) Common Toxicity Criteria Version 2.0 (Phase I)
Time Frame: Up to 6 months
Secondary Outcomes
- Dose-limiting toxicity (DLT) is defined as any grade 3 or higher hematologic or non-hematologic toxicity (Phase II)(Up to week 25)
- 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)
- 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)
- Interferon gamma production(Up to week 25)
- Infiltration of skin lesions by CD8+ cells(Up to week 25)
- Induction of apoptosis in infiltrating tumor cells in the skin(Up to week 26)