Ignite Creation Date:
2024-05-05 @ 9:11 PM
Last Modification Date:
2024-10-26 @ 10:01 AM
Study NCT ID:
NCT00839436
Status:
TERMINATED
Last Update Posted:
2015-10-15
First Post:
2009-02-06
Brief Title:
Interleukin-7 CYT107 Treatment of Idiopathic CD4 Lymphocytopenia Expansion of CD4 T Cells ICICLE
Sponsor:
National Institute of Allergy and Infectious Diseases NIAID
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Interleukin-7 CYT107 Treatment of Idiopathic CD4 Lymphocytopenia Expansion of CD4 T Cells ICICLE
Status:
TERMINATED
Status Verified Date:
2015-10
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Bankruptcy of Drug manufacturer Drug not available
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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
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 IIIa 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 cellsmicroL 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 IIIa 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 IIIa 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 cellsmicromL or less than 20 of lymphocytes deemed at risk for complications due to concurrent CD8 T cell lymphocytopenia andor 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 microgkg first 3 subjects-completed 10 microgkg next 5 subjects-completed and 20 microgkg 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
ICL was first characterized in the early 1990 s and is a primary immune disorder of CD4 T cell lymphocytopenia less than 300 cellsmicroL 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 IIIa 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 IIIa 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 cellsmicromL or less than 20 of lymphocytes deemed at risk for complications due to concurrent CD8 T cell lymphocytopenia andor 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 microgkg first 3 subjects-completed 10 microgkg next 5 subjects-completed and 20 microgkg 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
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 09-I-0069 | None | None | None |