Clinical Trial: Evaluating the Interest of Interleukine-2 for Patients With Active Warm Hemolytic Anemia Resistant to Conventional Treatment

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 Tr

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.

Detailed Summary:

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.

Sponsor: University Hospital, Bordeaux

Current Primary Outcome: Percentage of LTCD8+CD25highFoxp3+ . [ Time Frame: 9 weeks after inclusion ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

• 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
• 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
• 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.
• 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.
• 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

Original Secondary Outcome: Same as current

Information By: University Hospital, Bordeaux

Dates:
Date Received: February 13, 2015
Date Started: January 2017
Date Completion: December 2019
Last Updated: May 23, 2017
Last Verified: May 2017