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

Sponsor

University Hospital, Bordeaux (Other)

Overall Status

Completed

CT.gov ID

NCT02389231

Collaborator

(none)

Enrollment

Location

Arm

Actual Duration (Months)

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

2 participants

Allocation:

N/A

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 :

Nov 16, 2018

Actual Study Completion Date :

Nov 16, 2018

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

Percentage of LTCD8+CD25highFoxp3+ . [9 weeks after inclusion]
Increase of the percentage of LTCD8+CD25highFoxp3+ at the end of the IL2 treatment.

Secondary Outcome Measures

Incidence of complications with the treatment. [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 [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 [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. [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 [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