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Evaluating the Interest of Interleukine-2 for Patients With Active Warm Hemolytic Anemia Resistant to Conventional Treatment (ANEMIL)

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ClinicalTrials.gov Identifier: NCT02389231
Recruitment Status : Completed
First Posted : March 17, 2015
Last Update Posted : February 18, 2019
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux

Brief Summary:
The investigators have demonstrated that the mean percentage of circulating CD8+ regulatory T (CD8 Tregs) cells is significantly higher in patients with warm hemolytic anemia (wAHAI) in remission than in controls and is correlated to hemoglobin levels. In vitro, low dose of interleukine-2 (IL2) induce the expansion of CD8 Tregs. The objective is to demonstrate that, over a 9 week treatment period; low doses of IL2 can induce the expansion of CD8Tregs in patients with active wAHAI.

Condition or disease Intervention/treatment Phase
Autoimmune Hemolytic Anemia Drug: Interleukine-2 Phase 1 Phase 2

Detailed Description:

wAIHA is a B-cell-mediated autoimmune disease in which red blood cells are targeted by autoantibodies, which leads to marked decrease in their lifespan. The investigators demonstrated two years ago in a multivariate retrospective study that the CD3+CD8+ HLA-DR+ T-cell population was associated to a better outcome. The investigators observed that the proportion of circulating CD3+CD8+CD25highFoxp3+ T cells was significantly higher in patients with wAIHA in remission than in controls and correlated to hemoglobin levels. Extensive phenotyping and functional analysis revealed that those cells were bona fide Tregs acting in an IL10-dependent manner. Finally, culture of PBMC from normal donors or active wAIHAI patients with low dose of IL2 promoted the expansion of functional CD3+CD8+CD25+Foxp3+. Those observations constituted the rationale to propose low dose of IL2 to treat patients with active wAIHA with the objective of demonstrating that this treatment is able to induce the expansion of CD8Tregs, over a 9 week treatment period.

Four courses of IL2 (aldesleukin [Proleukin, Novartis]) will be administered subcutaneously for 5 days. The first course will be limited to a dose of 1.5 million IU per day and followed by a 9 day wash-out. The other courses of 3 million IU per day will be initiated after a 16 day wash-out.

Patients will be evaluated on day 1 and day 5 of each treatment course, before the first and last administration of interleukin-2 and will also be evaluated at 6 months.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 2 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: " Anemil Trial ": Phase I/II Clinical Trial Evaluating the Interest of Interleukine-2 for Patients With Active Warm Hemolytic Anemia Resistant to Conventional Treatment
Actual Study Start Date : May 17, 2017
Actual Primary Completion Date : November 16, 2018
Actual Study Completion Date : November 16, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Anemia

Arm Intervention/treatment
Experimental: Low doses of Interleukine-2
Low doses of Interleukine-2 over a 9 week treatment period
Drug: Interleukine-2

Four courses of IL2 ( [Proleukin, Novartis]) will be administered subcutaneously for 5 days.

The first course will be limited to a dose of 1.5 million IU per day and followed by a 9 day wash-out.

The other courses of 3 million IU per day will be initiated after a 16 day wash-out.

Other Names:
  • PROLEUKIN 18M
  • aldesleukine




Primary Outcome Measures :
  1. Percentage of LTCD8+CD25highFoxp3+ . [ Time Frame: 9 weeks after inclusion ]
    Increase of the percentage of LTCD8+CD25highFoxp3+ at the end of the IL2 treatment.


Secondary Outcome Measures :
  1. Incidence of complications with the treatment. [ Time Frame: 6 months after inclusion ]
    Safety of the treatment during the trial and 6 months after the inclusion

  2. Hemolysis as measured by hemoglobin, haptoglobin, reticulocytes and LDH levels [ Time Frame: 5 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion ]
    Impact of IL2 on hemolysis defined by hemoglobin, haptoglobin, reticulocytes, LDH levels

  3. Evaluation of lymphocyte sub-populations [ Time Frame: 5 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion ]
    Impact of IL2 on lymphocyte sub-populations (NK cells, B lymphocyte, CD4T lymphocyte, CD8T lymphocytes, CD4Tregs levels) at each time point of evaluation.

  4. Evaluation of lymphocyte activation. [ Time Frame: 5 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion ]
    Impact of IL2 on lymphocyte activation defined by DR expression at each time point of evaluation.

  5. Dose of steroid treatment [ Time Frame: 5 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion ]
    Impact of IL2 on steroid treatment (dose) during the trial and 6 months after the inclusion



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adults (18 years old)
  • wAHAI defined by the presence of hemolysis and positive coombs test (IgG +/-C3)
  • Absence of infection or other hematologic disease
  • wAHAI not responding to conventional steroids despite a dose over 10 mg
  • No treatment with rituximab for a minimum of 6 months
  • Signed informed consent form

Exclusion Criteria:

  • Less than 18 years old
  • Cold AHAI
  • IL2 allergy
  • Chemiotherapy or immunosuppressive treatment
  • Treatment with rituximab for less than 6 months
  • Neoplasia or hematologic malignancy
  • Aplastic anemia
  • Neutropenia ≤ 1000 mm3
  • Infection
  • Hepatitis B or C
  • wAHAI associated with systemic lupus erythematosus depending on ACR criteria
  • Cardiac insufficiency
  • Hypertension
  • Pulmonary insufficiency
  • Liver cirrhosis
  • Thrombopenia below 50000/mm3
  • Drug addiction, alcohol abuse
  • Psychiatric disorder
  • Absence of signed informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02389231


Locations
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France
CHU de Bordeaux Hôpital Haut Lévêque
Pessac, Aquitaine, France, 33604
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
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Principal Investigator: Estibaliz LAZARO, Prof University Hospital, Bordeaux
Study Chair: Rodolphe THIEBAUT, Prof University Hospital, Bordeaux

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Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT02389231     History of Changes
Other Study ID Numbers: CHUBX 2013/29
First Posted: March 17, 2015    Key Record Dates
Last Update Posted: February 18, 2019
Last Verified: February 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Bordeaux:
interleukine 2
warm autoimmune hemolytic anemia
CD8 regulatory T cells
Additional relevant MeSH terms:
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Anemia
Anemia, Hemolytic
Anemia, Hemolytic, Autoimmune
Hemolysis
Hematologic Diseases
Pathologic Processes
Autoimmune Diseases
Immune System Diseases
Aldesleukin
Interleukin-2
Antineoplastic Agents
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents