Idiopathic CD4+ T-Lymphocytopenia Clinical Trial
Official title:
Interleukin-7 (CYT107) Treatment of Idiopathic CD4 Lymphocytopenia: Expansion of CD4 T Cells (ICICLE)
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.
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.
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Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment