Interleukin-7 (CYT107) Treatment of Idiopathic CD4 Lymphocytopenia: Expansion of CD4 T Cells (ICICLE)

NCT00839436 | Terminated Phase 1 Results DMC

• 2 other identifiers: 09006909-I-0069
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Idiopathic CD4+ T-Lymphocytopenia

Keywords

Idiopathic CD4+ T-Lymphocytopenia; Interleukin-7; Clinical Trial; T-Lymphocytes; Idiopathic CD4 Lymphocytopenia (ICL); ICL

Outcome Measures

Primary Outcomes (1)

• Adverse Events and Toxicities Associated With CYT107.

  48 weeks per patient with a 3-4 year enrollment period

Other Outcomes (1)

• Change: CD4/CD8 T Cell Cts After CYT107; in Immunophenotype (Naive, Memory, Regulatory T Cell Subsets) & Amp; Antigen-specific T Cell Function After CYT107; in T Cell Activation/Proliferation Status & Amp; TCR Repertoire After CYT107; ...

  48 weeks per patient with a 3-4 year enrollment period

Study Arms (3)

3 microgram/kg CYT107

EXPERIMENTAL

3 microgram/kg CYT107

Drug: CYT107

10 microgram/kg CYT107

EXPERIMENTAL

10 microgram/kg CYT107

Drug: CYT107

20 microgram/kg CYT107

EXPERIMENTAL

20 microgram/kg CYT107

Drug: CYT107

Interventions

CYT107 DRUG

10 microgram/kg CYT107; 20 microgram/kg CYT107; 3 microgram/kg CYT107

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age greater than or equal to 18 years
• CD4 T cell count less than 300 cells/microL or less than 20% of total T lymphocytes on 2 occasions at least 6 weeks apart (and at the time of screening) in the absence of any illness accounting for CD4 lymphocytopenia
• ICL diagnosis that indicates a risk for disease progression, defined as one or both of the following:
• CD8 T cell lymphocytopenia (less than 180 cells/microL)
• History of opportunistic or otherwise significant infection (e.g., AIDS-defining or highly morbid illnesses, such as Cryptococcus or Mycobacteria infection, severe herpes zoster, JC virus causing progressive multifocal leukoencephalopathy, Kaposi s sarcoma, or severe human papilloma virus condylomata)
• HIV-1 and HIV-2 seronegativity and below detection of HIV-1 viral load
• HTLV-1 and HTLV-2 seronegativity
• Adequate venous access, as determined by the study team, although participants unable to undergo leukapheresis will not be excluded
• Normal thyroid-stimulating hormone (TSH)
• Negative serum or urine pregnancy test at time of study enrollment for women of childbearing potential
• Ability to understand and give informed consent
• Capacity and willingness to adhere to study procedures, including scheduled follow-up visits
• Willingness to allow blood and tissue sample storage
• Established primary care provider

You may not qualify if:

• History of prior cytotoxic, chemotherapeutic, immunosuppressant (e.g., systemic corticosteroids), immunomodulatory (e.g., IL-2, IL-7, interferon-gama), or growth factor therapy within the last 6 months; chemotherapy or immunomodulatory therapy given to treat an underlying disease or condition may be permitted at the protocol team's discretion, provided diagnosis of ICL was established prior to starting this treatment. The treatment has been stable for over 6 months and is being administered at stable doses as maintenance therapy.
• History of prior participation in another investigational intervention study within the last 6 months. Co-enrollment in other NIAID stem cell mobilization protocols will be permitted at the protocol team s discretion, but CYT107 may be dosed no sooner than 6 months after last dose of that protocol s medications have been given.
• Active uncontrolled opportunistic infection at the time of enrollment
• Current or recent history (less than 28 days prior to screening) of a viral, bacterial, parasitic or fungal infection requiring hospitalization and/or systemic treatment, other than long-term maintenance pharmacotherapy
• Serious illness requiring systemic treatment and/or hospitalization within 56 days (8 weeks) of screening, unless the subject is clinically stable, in the opinion of the Principal Investigator, and has completed therapy or has been on appropriate therapy for greater than 28 days (4 weeks) prior to screening
• Current or history of hematologic or lymphoid (lymphoma) malignancy
• Established or planned pregnancies or refusal to use effective birth control (e.g., barrier methods, oral contraceptives, intrauterine devices) for the duration of study involvement, regardless of gender
• Concurrent breastfeeding
• Renal insufficiency (e.g., estimated glomerular filtration rate less than 60 mL/min/1.73 m(2))
• Any of the following screening laboratory abnormalities: platelets less than 100,000 cells/microL; lipase greater than 1.5 times the ULN; AST, ALT, or alkaline phosphatase greater than 2.5 times the ULN; total bilirubin greater than 1.5 times the ULN
• History of splenectomy or hematologic disease associated with hypersplenism, such as alpha- or beta-thalassemia, hereditary spherocytosis, Gaucher s disease, or autoimmune hemolytic anemia
• Cirrhosis of any origin, including alcoholic or non-alcoholic steatohepatitis, either suspected by history or histologically proven
• History of hepatitis B or C infection, i.e., positive hepatitis B surface antigen, positive anti-hepatitis B core antibody with a detectable hepatitis B DNA viral load, positive anti-hepatitis C antibody and/or detectable hepatitis C RNA viral load (subjects who became negative for hepatitis B DNA or hepatitis C RNA following anti-viral treatment will not qualify for study treatment)
• Need for anticoagulant medication (e.g., warfarin, heparin), other than aspirin, clopidogrel, or other antiplatelet agent as CYT107 may co-precipitate with heparin if taken together.
• Active drug or alcohol use or dependence that, in the opinion of the investigator, would interfere with adherence to study requirements (subjects must agree to refrain from substance abuse use during the entire course of the study)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Smith DK, Neal JJ, Holmberg SD. Unexplained opportunistic infections and CD4+ T-lymphocytopenia without HIV infection. An investigation of cases in the United States. The Centers for Disease Control Idiopathic CD4+ T-lymphocytopenia Task Force. N Engl J Med. 1993 Feb 11;328(6):373-9. doi: 10.1056/NEJM199302113280601.

  PMID: 8093633 BACKGROUND

• Walker UA, Warnatz K. Idiopathic CD4 lymphocytopenia. Curr Opin Rheumatol. 2006 Jul;18(4):389-95. doi: 10.1097/01.bor.0000231908.57913.2f.

  PMID: 16763460 BACKGROUND

• Bofill M, Janossy G, Lee CA, MacDonald-Burns D, Phillips AN, Sabin C, Timms A, Johnson MA, Kernoff PB. Laboratory control values for CD4 and CD8 T lymphocytes. Implications for HIV-1 diagnosis. Clin Exp Immunol. 1992 May;88(2):243-52. doi: 10.1111/j.1365-2249.1992.tb03068.x.

  PMID: 1349272 BACKGROUND

• Sheikh V, Porter BO, DerSimonian R, Kovacs SB, Thompson WL, Perez-Diez A, Freeman AF, Roby G, Mican J, Pau A, Rupert A, Adelsberger J, Higgins J, Bourgeois JS Jr, Jensen SM, Morcock DR, Burbelo PD, Osnos L, Maric I, Natarajan V, Croughs T, Yao MD, Estes JD, Sereti I. Administration of interleukin-7 increases CD4 T cells in idiopathic CD4 lymphocytopenia. Blood. 2016 Feb 25;127(8):977-88. doi: 10.1182/blood-2015-05-645077. Epub 2015 Dec 16.

  PMID: 26675348 DERIVED

MeSH Terms

Conditions

T-Lymphocytopenia, Idiopathic CD4-Positive

Condition Hierarchy (Ancestors)

Lymphopenia; Leukopenia; Cytopenia; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukocyte Disorders; Immunologic Deficiency Syndromes; Immune System Diseases

Results Point of Contact

• Title: Dr. Virginia Sheikh
• Organization: NIAID

sheikhv@niaid.nih.gov

3014357939

Study Officials

• Virginia M Sheikh, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2009
• First Posted: February 9, 2009
• Study Start: February 1, 2009
• Primary Completion: May 1, 2014
• Study Completion: September 1, 2014
• Last Updated: October 15, 2015
• Results First Posted: October 15, 2015

Record last verified: 2015-10

Locations

US (1)