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Phase I Trial of Twice Weekly IV IL-12 Plus Low-Dose Subcutaneous IL-2 in Patients With Advanced Malignancies

Phase 1
18 Years
Not Enrolling
Unspecified Adult Solid Tumor, Protocol Specific

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Trial Information

Phase I Trial of Twice Weekly IV IL-12 Plus Low-Dose Subcutaneous IL-2 in Patients With Advanced Malignancies


I. To determine the toxicity profile and MTD of low-dose SC IL-2 administered in conjunction
with BIW regimen of IV rhIL-12.

II. To determine the antitumor effects of combination therapy with IV rhIL-12 and SC IL-2.

III. To determine the impact low-dose SC IL-2 has on the magnitude and duration of in vivo
immune activation induced by a BIW schedule of IV rhIL-12.

OUTLINE: This is a dose-escalation study.

Patients receive interleukin-12 (IL-12) IV on days 1 and 4 for 6 weeks. Beginning on day 4
of the third week, patients receive interleukin-2 (IL-2) subcutaneously 1 hour before and 20
hours after each dose of IL-12. On subsequent courses, IL-2 and IL-12 are administered on
days 1 and 4 of each week. Treatment continues for 6 weeks in the absence of disease
progression or unacceptable toxicity. Patients with disease response may continue treatment
until complete response or disease progression.

Cohorts of 3-6 patients receive escalating doses of IL-12 and IL-2 until the maximum
tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2
of 6 patients experience dose-limiting toxicity.

Patients are followed at 3 weeks.

Inclusion Criteria:

- Patients must have a histologically confirmed solid tumor malignancy which is
metastatic or unresectable and for which standard curative or palliative measures do
not exist or are no longer effective; patients with hematologic malignancies will be

- Patients must have advanced measurable or evaluable disease which is clearly

- Patients must be ambulatory with good performance status (ECOG PS 0 or 1; Karnofsky
PS 100-80%) and have an anticipated survival of at least 3 months

- Women of child bearing potential must have a negative pregnancy test and will be
expected to use proven contraceptive methods while on protocol therapy; women who are
breast-feeding are excluded from this study

- WBC > 4000/mm^3

- ANC > 1500/mm^3

- Platelet count > 100,000/mm^3

- Bilirubin < 1.5 mg/dl

- SGOT, SGPT < 2 x normal

- Creatinine < 1.5 mg/dl or calculated creatinine clearance >= 60 ml/min

- No evidence of congestive heart failure, symptoms of coronary artery disease, serious
cardiac arrhythmias, or evidence of prior myocardial infarction on EKG

- No evidence of active infection which requires antibiotic therapy or history of
treatment with IV antibiotics for a documented infection within 2 weeks of beginning

- Patients must have recovered from the toxicity of prior therapy and have clearly
progressive disease

- CHEMO, HORMONAL, AND RADIOTHERAPY There is a limit of two prior chemotherapy regimens
which patients may have received; (patients who have received extensive prior
cytotoxic therapy may no longer have adequate organ function and may not be
eligible); at least 4 weeks must have elapsed from the end of previous chemotherapy,
hormonal therapy, or radiotherapy (six weeks for nitrosoureas or mitomycin);
concurrent chemotherapy, hormonal therapy or radiotherapy is not permitted; patients
on steroids, including replacement therapy, will be excluded from the study

- BIOLOGICAL RESPONSE MODIFIERS No more than 2 prior BRM treatment regimens are
permitted; prior immunotherapy should have been completed at least 4 weeks prior to
beginning treatment on this protocol; prior therapy will IL-2 or rhIL-12 is allowable
if >= 6 months have elapsed since the end of IL-2 treatment or if >= 12 months have
elapsed since rhIL-12 therapy

- The patient must give signed informed consent prior to the initiation of therapy;
patients with a history of major psychiatric illness must be judged able to fully
understand the investigational nature of the study and the risks associated with

- Patients with the following problems will be considered ineligible:

- Organ allografts

- Brain metastases

- Seizure disorders

- Patients known to be HIV positive are excluded based on the potential harm
these agents may have on their underling immune function and the unknown
effects of combination therapy with IL-12 and IL-2 on HIV viral
replication; in addition, HIV infection, through its documented deleterious
effects on lymphocyte number and function, may impair the patient's ability
to respond to this form of cytokine-based immunotherapy

- Any medical condition likely to require use of corticosteroids during IL-12

- Autoimmune or rheumatologic disease

- Active (clinical or subclinical) hepatitis B or hepatitis C infection

- Any significant medical disease other than the malignancy felt by the
investigator to place the patient at greater risk for developing a
life-threatening toxicity from the therapy

Type of Study:


Study Design:

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

Outcome Measure:

MTD defined as the dose level that is just below the dose on which at least 2 of 6 patients developed a dose-limiting toxicity (DLT) as assessed by CTC version 2.0

Outcome Time Frame:

6 weeks

Safety Issue:


Principal Investigator

Michael Atkins

Investigator Role:

Principal Investigator

Investigator Affiliation:

Beth Israel Deaconess Medical Center


United States: Food and Drug Administration

Study ID:




Start Date:

March 2000

Completion Date:

Related Keywords:

  • Unspecified Adult Solid Tumor, Protocol Specific



Beth Israel Deaconess Medical Center Boston, Massachusetts  02215