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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


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Stage I Cutaneous T-cell Non-Hodgkin Lymphoma, Stage I Mycosis Fungoides/Sezary Syndrome, Stage II Cutaneous T-cell Non-Hodgkin Lymphoma, Stage II Mycosis Fungoides/Sezary Syndrome, Stage III Cutaneous T-cell Non-Hodgkin Lymphoma, Stage III Mycosis Fungoides/Sezary Syndrome, Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma, Stage IV Mycosis Fungoides/Sezary Syndrome

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Trial Information

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


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.


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

Type of Study:

Interventional

Study Design:

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

Outcome Measure:

Clinical response rate defined as the percentage of patients who achieve complete or partial response (Phase I)

Outcome Time Frame:

Up to week 13

Safety Issue:

No

Principal Investigator

Alain Rook

Investigator Role:

Principal Investigator

Investigator Affiliation:

Abramson Cancer Center of the University of Pennsylvania

Authority:

United States: Food and Drug Administration

Study ID:

NCI-2012-02504

NCT ID:

NCT00052377

Start Date:

September 2002

Completion Date:

Related Keywords:

  • Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma
  • Recurrent Mycosis Fungoides/Sezary Syndrome
  • Stage I Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage I Mycosis Fungoides/Sezary Syndrome
  • Stage II Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage II Mycosis Fungoides/Sezary Syndrome
  • Stage III Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage III Mycosis Fungoides/Sezary Syndrome
  • Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma
  • Stage IV Mycosis Fungoides/Sezary Syndrome
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Mycoses
  • Mycosis Fungoides
  • Sezary Syndrome
  • Lymphoma, T-Cell
  • Lymphoma, T-Cell, Cutaneous

Name

Location

Abramson Cancer Center of the University of PennsylvaniaPhiladelphia, Pennsylvania  19104-4283