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

February 15, 2019 updated by: University Hospital, Bordeaux

" Anemil Trial ": Phase I/II Clinical Trial Evaluating the Interest of Interleukine-2 for Patients With Active Warm Hemolytic Anemia Resistant to Conventional Treatment

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

2

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
    • Aquitaine
      • Pessac, Aquitaine, France, 33604
        • CHU de Bordeaux Hopital Haut leveque

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of LTCD8+CD25highFoxp3+ .
Time Frame: 9 weeks after inclusion
Increase of the percentage of LTCD8+CD25highFoxp3+ at the end of the IL2 treatment.
9 weeks after inclusion

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
6 months after 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
5 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion
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.
5 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion
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 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion
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
5 days, 20 days, 40 days, 61 days, 63 days and 6 months after inclusion

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Bordeaux

Investigators

  • Principal Investigator: Estibaliz LAZARO, Prof, University Hospital, Bordeaux
  • Study Chair: Rodolphe THIEBAUT, Prof, University Hospital, Bordeaux

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 17, 2017

Primary Completion (Actual)

November 16, 2018

Study Completion (Actual)

November 16, 2018

Study Registration Dates

First Submitted

February 13, 2015

First Submitted That Met QC Criteria

March 9, 2015

First Posted (Estimate)

March 17, 2015

Study Record Updates

Last Update Posted (Actual)

February 18, 2019

Last Update Submitted That Met QC Criteria

February 15, 2019

Last Verified

February 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHUBX 2013/29

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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