Clinical Trial: Phase I Study of Interleukin-7 (CYT 99 007) in Patients with Advanced Cancers

This study is currently recruiting patients.

Sponsored by: National Cancer Institute (NCI)
Information provided by: Warren G Magnuson Clinical Center (CC)

Purpose

This study will 1) determine the highest dose of Interleukin-7 (CYT 99 07) that can safely be given to cancer patients; 2) determine how the body absorbs and eliminates the drug; and 3) examine the side effects and possible benefits of the drug in these patients. CYT 99 07 is intended to boost patients' immune systems. Patients with cancer often develop immune deficiencies, mostly caused by chemotherapy or radiation treatment.

Patients 18 years of age and older with cancer that cannot be treated successfully with standard therapy may be eligible for this study. Patients with cancers of the blood and lymph system and patients with primary lung cancer are excluded from the study. Candidates will be screened with a medical history, physical and eye examinations; blood tests; electrocardiogram (EKG) and MUGA (nuclear medicine test of heart function); chest x-ray; chest, abdomen, and pelvic CT or MRI scans; and other studies as needed to evaluate their disease.

Participants will receive an injection of CYT 99 07 every other day for 2 consecutive weeks, for a total of eight doses. The first three patients entering the study will receive the lowest of five study doses, and the dose will be increased gradually in groups of three patients as long as unacceptable side effects do not develop.

While receiving treatment, patients will be evaluated with daily blood tests and weekly physical examinations. Additional procedures include bone marrow biopsies, chest x-rays, EKGs and CT scans. After the 2-week treatment period, patients will be followed at least once a week for 2 additional weeks. The follow-up visits will include a physical examination, chest x-ray, EKG, and blood tests.

Patients who show abnormalities in their physical examination or laboratory studies may be asked to return for blood tests beyond the 28-day study period in order to follow the course of the abnormalities.

Condition Treatment or Intervention Phase
Non-Hematologic Neoplasms
 Drug: CYT 99 007 (Recombinant Human Interleukin-7)
 Drug: CYT99007
Phase I

MedlinePlus consumer health information 

Study Type: Interventional
Study Design: Treatment, Safety

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

Further Study Details: 

Expected Total Enrollment:  30

Study start: April 10, 2003

Interleukin-7 (IL-7) has a wide range of biological activities that makes it one of the pivotal interleukins. Critical roles are described in rodents, not only in T-cell and B-cell developments but also in hematopoiesis and in post developmental immune functions. The biological activities appear to be directed more towards T-cell functions in humans and non-human primates as compared to the mouse where IL-7 also contributes considerably to the B-cell development and physiology.

Interleukin-7 may prove extremely valuable in therapy for T-cell homeostasis in condition disease induced lymphocyte depletion (HIV) as well as iatrogenic states of immune deficiencies such as post-chemotherapy and post-hematopoietic stem cell transplant immune reconstitution.

This study has a clinical phase I, dose escalation design. CYT 99 007 (recombinant human IL-7 provided by Cytheris Corporation) will be administered every other day, by intermittent subcutaneous injection for two consecutive weeks (for a total of eight injections).

The primary objective is to determine the safety and, possibly, dose-limiting toxicity of biologically active recombinant human IL-7 in the context of malignancy refractory to conventional therapies.

Secondary objectives are to identify a range of biologically active dose of CYT 99 007 (rhIL-7) and characterize a range of biological effects of IL-7 as defined in the study end-points. Possible anti-tumor effects of CYT 99 007 will also be examined in the context of this dose escalation strategy.

Eligibility

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Age greater than or equal to 18 years.
Diagnosis of a malignancy, histologically confirmed by the Laboratory of Pathology of each participating center.
Patients must be considered to have an incurable malignancy and have failed standard therapy for their disease. Failure can be defined as either lack of response or progression (25% increase in disease or new disease).
Patients must have measurable or evaluable disease.
Ejection fraction greater than 45% by MUGA.
DLCO/VA and FEV1 greater than 50% of predicted on pulmonary function tests.
AST and ALT less than 3 x the upper limit of normal.
Absolute Neutrophil Count greater than 1000/mm(3).
Platelets greater than 100,000/mm(3).
PT/PTT within 1.5 x upper limit of normal.
Karnofsky performance status greater than 70%.
Creatinine Clearance of greater than 60 cc/min.
Patients must have a stable CD3+ cells count greater than 300 cells per mm(3) in the peripheral blood (on 4 successive determinations over a period of no more than two weeks) immediately prior to entry on study. Stable is defined as a coefficient of variation (Standard Deviation divided by the mean) of 20% or less. The fourth determination will determine the on-study date.
Patients must not have received any systemic corticosteroids therapy for more than 72 hours in the two weeks prior to the start of the 4 peripheral CD3 count determinations.
Patients must not have received any cytotoxic therapy, immunotherapy by cytokines, anti-tumor vaccines or monoclonal antibody in the four weeks prior to the start of the 4 peripheral CD3 count determinations.
EXCLUSION CRITERIA:
Any subject with a potentially curable malignancy who has not yet received all appropriate standard therapies of known curative potential.
If it becomes obvious during the course of the evaluation that a therapy incompatible with this study's eligibility criteria is in the candidate's best interest, he or she will be immediately withdrawn from consideration for the study to be treated appropriately.
Hematopoietic malignancies.
Primary carcinoma of the lung.
Life expectancy of less than three months.
Documented HIV, hepatitis B, or hepatitis C infection. A positive hepatitis B serology indicative of previous immunization (i.e. HBs Ab positive and HBc Ab negative) is not an exclusion criterion. A positive hepatitis C serology is an exclusion criterion.
Concurrent cytotoxic or immunosuppressive therapies.
Medical need for chronic anticoagulation (coumadin 1 to 2 mg is acceptable, heparin not acceptable)
Patients with a resting blood pressure greater than 140/90, in presence of standard anti-hypertensive therapy. Untreated hypertensive patients may be given a trial of standard anti-hypertensive therapy and, if their hypertension is well controlled, may be allowed to enter the study.
Current need for palliative therapy as determined by the principal investigator.
History of autoimmune disease.
History of severe asthma, presently on chronic medications.
Prior allogeneic Hematopoietic Stem Cell transplantation or solid organ transplantation.
Patients with splenectomy.
Current splenomegaly or proliferative hematologic disease.
Inability or refusal to practice contraception during therapy or pregnancy.
History of medical or psychiatric disease which, in the view of the principal investigator, would preclude safe treatment.
Patient with cognitive impairment or likely to develop cognitive impairment while on study.
Inability to give informed consent.

Location and Contact Information


Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting
Patient Recruitment and Public Liaison Office  1-800-411-1222    prpl@mail.cc.nih.gov 
TTY  1-866-411-1010 

More Information

Detailed Web Page

Publications

Goodwin RG, Lupton S, Schmierer A, Hjerrild KJ, Jerzy R, Clevenger W, Gillis S, Cosman D, Namen AE. Human interleukin 7: molecular cloning and growth factor activity on human and murine B-lineage cells. Proc Natl Acad Sci U S A. 1989 Jan;86(1):302-6.

Sakata T, Iwagami S, Tsuruta Y, Teraoka H, Tatsumi Y, Kita Y, Nishikawa S, Takai Y, Fujiwara H. Constitutive expression of interleukin-7 mRNA and production of IL-7 by a cloned murine thymic stromal cell line. J Leukoc Biol. 1990 Sep;48(3):205-12.

Sudo T, Ito M, Ogawa Y, Iizuka M, Kodama H, Kunisada T, Hayashi S, Ogawa M, Sakai K, Nishikawa S. Interleukin 7 production and function in stromal cell-dependent B cell development. J Exp Med. 1989 Jul 1;170(1):333-8.

Study ID Numbers:  030152; 03-C-0152
Record last reviewed:  March 3, 2005
Last Updated:  March 11, 2005
Record first received:  April 16, 2003
ClinicalTrials.gov Identifier:  NCT00059059
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

Resources