Clinical trial NCT00839436
Conditions: Idiopathic CD4+ T-Lymphocytopenia
Keywords: Idiopathic CD4+ T-Lymphocytopenia Interleukin-7 Clinical Trial T-Lymphocytes Idiopathic CD4 Lymphocytopenia (ICL) ICL
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Start date: 2009-02-01; Completion date: 2014-09-01
Enrollment: 21 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Background:

* Idiopathic CD4 lymphocytopenia (ICL) is a condition in which patients have low levels of T cells, a type of white blood cell that helps fight infection. Animal studies have shown that an experimental drug Interleukin 7 (IL-7), which is named CYT107, can increase the number and function of T cells. CYT107, however, has not been used in people with ICL.

Objectives:

* To determine the safety of CYT107 in people with ICL.
* To determine whether CYT107 will increase the number and function of T cells in people with ICL.

Eligibility:

* Patients 18 years of age and older diagnosed with ICL and who are at risk of becoming sick because of this condition are eligible for this study. In addition, patients must not be pregnant, or have other illnesses that would cause low CD4 T cell counts, such as human immunodeficiency virus (HIV) or human T-lymphotrophic virus (HTLV) infection.

Design:

* The initial screening visit will include the following examinations and tests:
* A complete physical exam and medical history
* Blood analysis, including CD4 T cell count; complete blood count and additional blood tests to determine clotting ability and blood composition; thyroid, liver, kidney, and pancreatic function tests; HIV and HTLV tests; and tests for anti-IL-7 antibodies that block normal IL-7 activity
* Routine urine test
* Urine or blood pregnancy test for women
* Chest X-ray
* Electrocardiogram
* Spleen ultrasound.
* The baseline visit will include blood tests to determine levels of each of the major types of antibodies, a test of genetic background, and more detailed CD4 and protein analysis. In addition, leukapheresis (a procedure to collect large numbers of immune cells without red blood cells) will be done. Participants will also have the option of having colon and lymph node biopsies.
* The schedule will be as follows:
* Weeks 1, 2, and 3 (Cycle 1): Three weekly IL-7 dosing visits.
* Weeks 5, 8, and 12: Follow-up visits.
* Weeks 24, 25, and 26 (Cycle 2): Three more weekly IL-7 dosing visits.
* Weeks 28, 31, and 35: Follow-up visits.
* Week 48: End of study visit.
* Tests conducted before getting IL-7 will be repeated during the IL-7 cycles and follow-up visits to compare with earlier values. Optional colon and lymph node biopsies done at baseline will be repeated 1 6 weeks prior to Cycle 2 and 1 6 weeks prior to Week 48.

Detailed description:
Interleukin-7 (CYT107) Treatment of Idiopathic CD4 Lymphocytopenia: Expansion of CD4 T Cells (ICICLE) is a Phase I/IIa open-label, single arm clinical trial evaluating the safety profile of glycosylated recombinant human interleukin-7 (rhIL-7) as an immunostimulatory therapy in patients with idiopathic CD4 T cell lymphocytopenia (ICL) at risk of disease progression. Secondary analyses will assess the immunostimulatory effects of rhIL-7 on T cell number and function.

ICL was first characterized in the early 1990 s and is a primary immune disorder of CD4 T cell lymphocytopenia (less than 300 cells/microL or less than 20% of lymphocytes), which is not due to any known infectious process, exogenous medication, autoimmune cytopenia, or other underlying disorder associated with lymphocytopenia. ICL patients are at risk for a wide spectrum of opportunistic and other serious infections, autoimmune disorders, and other types of lymphocytopenia. At present, no validated treatment exists for ICL, and treatment is directed primarily toward infectious complications once they arise. A first-generation form of rhIL-7 was shown in pre-clinical and Phase I studies in oncology and human immunodeficiency virus (HIV)-infected patients to be well tolerated in repeated dose trials, with long-lasting increases in both CD4 and CD8 T cells. CYT107 is a second-generation rhIL-7 product made by Cytheris via a recombinant mammalian cell culture system.

DESIGN - Open-label, single-arm, Phase I/IIa interventional clinical trial. Participants will be evaluated at baseline (prior to study treatment) and according to the protocol follow-up schedule, receiving a total of 2 cycles of rhIL-7 (CYT107) during the induction phase and up to 8 cycles during the maintenance phase. Safety assessments of rhIL-7 will be the primary focus at each study visit, with secondary analyses of immune parameters, including changes from baseline in T cell number and function at Weeks 24 and 48.

DURATION - Enrollment is expected to take 3 to 4 years. Each volunteer will be followed for at least 48 weeks. Thus, total duration of the study will be approximately 5 years.

SAMPLE SIZE - Approximately 35-40 patients will be screened over a 3-year period to achieve the desired sample of 18 ICL patients, allowing for a primary safety assessment of CYT107 in this Phase I/IIa clinical trial, as well as exploring the immunomodulatory effects of rhIL-7.

POPULATION - Men and women, aged greater than or equal to 18 years, with a confirmed diagnosis of ICL (CD4 less than 300 cells/micromL or less than 20% of lymphocytes) deemed at risk for complications due to concurrent CD8 T cell lymphocytopenia and/or history of opportunistic or otherwise serious infection, without autoimmunity or hematologic or lymphoid malignancy.

REGIMEN - During the induction phase, subjects will receive 2 cycles of subcutaneous rhIL-7 dosed once weekly for 3 weeks in a dose escalation fashion: 3 microg/kg (first 3 subjects-completed), 10 microg/kg (next 5 subjects-completed) and 20 microg/kg (last 5 subjects), with an additional 5 subjects at the highest achieved dose level. Cycles of rhIL-7 will be administered starting at Week 1 and Week 24.

For subjects who tolerate the induction phase and elect to participate in the

maintenance phase, additional cycles of rhIL-7 may be offered at 3-6 month

intervals. These participants will receive rhIL-7 at the highest dose for which at

least 8 weeks of safety data for 5 subjects has been reviewed provided no more

than 1 DLT is reported.

Arms: arm 1: 3 microgram/kg CYT107 arm 2: 10 microgram/kg CYT107 arm 3: 20 microgram/kg CYT107
Interventions: intervention 1: CYT107
Intervention descriptions: intervention 1: None

Protocol documents: