Interleukin-7 in Treating Patients With Refractory Solid Tumors

A Phase I Study of Subcutaneous "CYT 99 007" (Interleukin-7) in Patients With Refractory Non Hematologic Malignancy

RATIONALE: Interleukin-7 may stimulate a person's white blood cells to kill tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of interleukin-7 in treating patients with refractory solid tumors.

OBJECTIVES:

• Determine the safety and dose-limiting toxicity of biologically active doses of interleukin-7 in patients with refractory solid tumors.
• Determine a range of biologically active doses of this drug in these patients.
• Determine the biological effects of this drug in these patients.
• Determine the pharmacokinetics and pharmacodynamics of this drug in these patients.
• Determine the antitumor effects of this drug in these patients.

OUTLINE: This is a multicenter, dose-escalation study.

Patients receive interleukin-7 (IL-7) subcutaneously on days 0, 2, 4, 6, 8, 10, 12, and 14 (for a total of 8 doses) in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of IL-7 until the maximum tolerated dose (MTD) and "biologically active dose" (BAD) are determined. The MTD is defined as the dose preceding that at which at least 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. The BAD is defined as the dose that produces a sustained 50% increase in CD3+ count over the patient's baseline without unacceptable toxicity.

Patients are followed at 1, 3, and 6 months and at 1 year after study completion.

PROJECTED ACCRUAL: A total of 15-30 patients will be accrued for this study within 3.75-10 months.

DISEASE CHARACTERISTICS:

• Histologically confirmed malignancy meeting both of the following criteria:

  • No known curative therapy
  • Failed standard therapy, defined as either lack of response OR disease progression (i.e., at least 25% increase in disease or new disease)

• Measurable or evaluable disease

• No hematopoietic malignancies

• No primary carcinoma of the lung

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• Karnofsky 80-100%

Life expectancy

• At least 3 months

Hematopoietic

• Absolute neutrophil count greater than 1,000/mm^3
• Platelet count greater than 100,000/mm^3
• No proliferative hematologic disease

Hepatic

• AST and ALT less than 3 times upper limit of normal (ULN)
• PT/PTT no greater than 1.5 times ULN
• No documented hepatitis B infection
• No documented hepatitis C infection

Renal

• Creatinine clearance greater than 60 mL/min

Cardiovascular

• Ejection fraction greater than 45% by MUGA
• Hypertension (resting blood pressure greater than 140/90 mm Hg) must be controlled with standard anti-hypertensive therapy

Pulmonary

• No severe asthma
• DLCO/VA greater than 50% of predicted
• FEV_1 greater than 50% of predicted

Immunologic

• No autoimmune disease
• Peripheral CD3+ cell count greater than 300/mm^3 and stable on 4 successive determinations
• HIV negative

Other

• Not pregnant
• Negative pregnancy test
• Fertile patients must use effective contraception
• No other medical or psychiatric condition that would preclude study compliance
• No cognitive impairment or likelihood of developing cognitive impairment during study participation
• No need for palliative therapy
• No splenomegaly

PRIOR CONCURRENT THERAPY:

Biologic therapy

• More than 4 weeks since prior immunotherapy by cytokines, anti-tumor vaccines, or monoclonal antibody therapy prior to the initiation of peripheral CD3 count determination
• No prior allogeneic hematopoietic stem cell transplantation
• No other concurrent immunotherapy
• No other concurrent biologic agents (e.g., growth factors or monoclonal antibodies)

Chemotherapy

• No concurrent chemotherapy

Endocrine therapy

• No prior systemic corticosteroid therapy for more than 72 hours within the 2 weeks prior to initiation of peripheral CD3 cell count determination
• No concurrent chronic steroid therapy

Radiotherapy

• Not specified

Surgery

• No prior solid organ transplantation
• No prior splenectomy

Other

• More than 4 weeks since prior cytotoxic therapy prior to the initiation of peripheral CD3 cell count determination

• No concurrent cytotoxic therapy

• No concurrent immunosuppressive therapy

• No concurrent medications for the treatment of hypertension

• No concurrent chronic asthma medications

• No concurrent chronic anticoagulants (e.g., high-dose warfarin, heparin, or aspirin)

  • Low-dose oral warfarin allowed