Lymphocyte Infusions for the Treatment of HIV-Infected Patients Failing Anti-HIV Therapy

NCT00559416 | Terminated Phase 1

• 2 other identifiers: 08002408-CC-0024
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Some HIV-infected individuals have a white blood cell marker known as HLA-B\*57 that appears to help control the progress of the disease; however, not all who have the HLA-B\*57 marker are able to control the infection. This study will examine the effects of giving white blood cells with HLA-B\*57 from an individual who controls HIV infection to an individual who cannot control HIV infection, as a form of HIV treatment. All candidates will be screened with a medical history, physical examination, and blood and urine tests. Both donor and recipient volunteers must be HIV-positive individuals 18 years of age or older who have the HLA-B\*57 marker and are receiving care. Donor candidates must have positive HIV antibody tests for at least seven years with a recent CD4 cell count greater than 400 cells/mm?, HIV viral load less than 50 copies/mL, and no previous HIV viral load greater than 1,000 copies/mL. Recipient candidates must have positive HIV antibody tests with a recent CD4 cell count less than 400 cells/mm? and HIV viral load greater than 10,000 copies/mL, and must have failed at least two prior combination antiretroviral regimes and are willing to receive or resume combination antiretroviral therapy. Donor volunteers will be excluded if they have taken certain antiretrovirals drugs, have a medical history of cancer or of other blood-borne illnesses, or have other medical conditions that might interfere with the study. Recipient volunteers will be excluded if they have a medical history of malignant cancer or other medical conditions that might possibly interfere with the study. Donors will undergo apheresis to separate white blood cells from circulating blood before the red blood cells and plasma are returned to the bloodstream. The procedure will take up to five hours, and donors will be required to return for additional tests. Donors may be asked to return for further white blood cell donations, a maximum of six procedures per year. Recipients will undergo apheresis to obtain stem cells for possible use in the study, and will be admitted to an NIH Clinical Center inpatient unit to receive an infusion of white blood cells and undergo a series of blood tests both before and after the infusion. The infusion process will take two hours. After being discharged, recipients will be asked to return to the Clinical Center for monitoring and follow-up tests, and may receive further infusions.

Conditions

HIV Infections

Keywords

HIV/AIDS; HLA-B*57; Cell Transfer; HIV; treatment experienced

Outcome Measures

Primary Outcomes (1)

• Safety, survival of transferred cells.

Secondary Outcomes (1)

• Changes in immune and viral parameters (CD4, Plasma HIV levels)

Interventions

Cell Transfer DRUG

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Under this protocol, cell recipients must fulfill all of the following characteristics and conditions:
• Greater than or equal to 18 years old
• Ability to sign informed consent
• For women of child-bearing potential, negative result on a serum or urine pregnancy test; in addition, men and women of childbearing potential must agree to practice abstinence or use two methods of birth control/contraception (condoms, diaphragm or cervical cap with spermicide, IUD, or hormonal-based contraception) for at least 4 weeks after each cell infusion
• Willingness to comply with study requirements and procedures including storage of blood for possible future use to study HIV/AIDS, related diseases, or the immune system
• Willingness to permit HLA testing
• Hematocrit greater than or equal to 27 percent, platelets greater than or equal to 25,000/mm (3)
• No significant underlying cardiac, renal, or hepatic disease (Creatinine less than 2.0 mg/dL; aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than 150 U/mL)
• HIV infection must be confirmed by ELISA and a confirmatory test (e.g. western blot if not previously documented, and patients must be under the care of a primary care physician.
• Viral load greater than 10,000 copies/mL on available optimized combination antiretroviral therapy, to include at least 3 drugs, one of which is a non-nucleoside reverse transcriptase inhibitor (NNRTI), integrase inhibitor, or protease inhibitor. Patients not on combination antiretroviral therapy will be eligible, but must be willing to resume combination antiretroviral therapy and to have had a viral load greater than 10,000 copies/mL after at least 2 weeks of therapy.
• Failure or intolerance of at least two previous combination antiretroviral regimens. Failure will be defined as an HIV viral load greater than 400 copies/mL while taking a given regimen.
• Recipient must be taking appropriate prophylaxis for opportunistic infections, as per Public Health Service (PHS) guidelines, unless there is intolerance to available medications.
• Screening CD4+ cell count less than or equal to 350 cells/mm(3) obtained within 6 weeks prior to study entry.

You may not qualify if:

• An individual will be ineligible to receive cells if one or more of the following conditions are present:
• Discordance with donor on antibody status of EBV, CMV, or HHV-8 if donor is antibody positive for EBV, CMV, or HHV-8.
• Malignancy requiring systemic therapy, or a history of malignancy that required myelotoxic chemotherapy.
• Active untreated opportunistic infection that requires systemic therapy. Patients with opportunistic infections who have received greater than 2 weeks of therapy will be eligible.
• Is pregnant or breast feeding.
• Severe psychiatric disorder that would interfere with adherence to protocol requirements. Individuals who have a stable psychiatric condition may be eligible.
• Current use or a history of treatment with investigational agent(s) within 3 months of protocol enrollment. ARVs obtained through expanded access programs are permitted.
• Current use or a history of treatment with a systemic corticosteroid, immunosuppressive, or cytotoxic agent within 30 days of protocol enrollment.
• Any other medical condition for which the investigator believes cell transfer may be contraindicated.
• Ever been diagnosed with autoimmune vasculitis.
• Donor eligibility criteria as specified by the FDA will be followed, except for HIV testing. All donors will be HIV positive as per protocol and as described in the IND application. Under this protocol, cell donors must fulfill all of the following characteristics and conditions:
• Greater than or equal to 18 years old.
• Ability to sign informed consent.
• For women of child-bearing potential, negative result on a serum or urine pregnancy test.
• Willingness to comply with study requirements and procedures including storage of blood for possible future use to study HIV/AIDS, related diseases, or the immune system.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Coffin JM. HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science. 1995 Jan 27;267(5197):483-9. doi: 10.1126/science.7824947.

  PMID: 7824947 BACKGROUND

• Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax PE, Kalams SA, Walker BD. Vigorous HIV-1-specific CD4+ T cell responses associated with control of viremia. Science. 1997 Nov 21;278(5342):1447-50. doi: 10.1126/science.278.5342.1447.

  PMID: 9367954 BACKGROUND

• Kovacs JA, Lempicki RA, Sidorov IA, Adelsberger JW, Sereti I, Sachau W, Kelly G, Metcalf JA, Davey RT Jr, Falloon J, Polis MA, Tavel J, Stevens R, Lambert L, Hosack DA, Bosche M, Issaq HJ, Fox SD, Leitman S, Baseler MW, Masur H, Di Mascio M, Dimitrov DS, Lane HC. Induction of prolonged survival of CD4+ T lymphocytes by intermittent IL-2 therapy in HIV-infected patients. J Clin Invest. 2005 Aug;115(8):2139-48. doi: 10.1172/JCI23196. Epub 2005 Jul 14.

  PMID: 16025158 BACKGROUND

• Migueles SA, Chairez C, Lin S, Gavil NV, Rosenthal DM, Pooran M, Natarajan V, Rupert A, Dewar R, Rehman T, Sherman BT, Adelsberger J, Leitman SF, Stroncek D, Morse CG, Connors M, Lane HC, Kovacs JA. Adoptive lymphocyte transfer to an HIV-infected progressor from an elite controller. JCI Insight. 2019 Sep 19;4(18):e130664. doi: 10.1172/jci.insight.130664.

  PMID: 31415245 DERIVED

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Study Officials

• Joseph A Kovacs, M.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: November 15, 2007
• First Posted: November 16, 2007
• Study Start: November 8, 2007
• Primary Completion: September 30, 2016
• Study Completion: September 30, 2016
• Last Updated: July 5, 2018

Record last verified: 2016-09-30

Locations

US (1)