A Phase I Study of Subcutaneous "CYT 99 007" (Interleukin-7) in Patients With Refractory Non Hematologic Malignancy
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Study of Subcutaneous "CYT 99 007" (Interleukin-7) in Patients With Refractory Non Hematologic Malignancy
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Claude Sportes, MD
Investigator Role:
Study Chair
Investigator Affiliation:
National Cancer Institute (NCI)
Authority:
United States: Food and Drug Administration
Study ID:
030152
NCT ID:
NCT00062049
Start Date:
April 2003
Completion Date:
May 2011
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
Name | Location |
|---|---|
| Methodist Hospital | Houston, Texas 77030 |
| Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office | Bethesda, Maryland 20892-1182 |
| NCI - Center for Cancer Research | Bethesda, Maryland 20892 |
