Amplifying Graft-Versus-Tumor Effect by Donor Regulatory T-Cell Depletion Before Donor Lymphocytes Infusion

Hematologic Neoplasms Clinical Trial

— ILD-Treg  

Official title:

Amplifying Graft-versus-tumor Effect by Donor Regulatory T-cell Depletion Before Donor Lymphocytes Infusion: a Phase I/II Clinical Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00987987
• Other study ID #: P040441
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: September 30, 2009
• Last updated: January 21, 2011
• Start date: December 2005
• Est. completion date: December 2009

Study information

• Verified date: September 2009
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

The investigators have previously shown that depletion of CD4+CD25+FoxP3+ regulatory T cells (Treg) enhances the alloreactivity of T lymphocytes, as attested by an accelerated GVHD after allogeneic hematopoietic stem cell transplantation (HSCT) in mice. The investigators thus propose a clinical trial to test whether Treg-depleted donor lymphocytes infusion (dDLI) could induce an improved graft-versus-tumor (GVT) effect in patients refractory to standard DLI (stdDLI) for treatment of relapse after HSCT.

Description:

We have previously shown that depletion of CD4+CD25+FoxP3+ regulatory T cells (Treg) enhances the alloreactivity of T lymphocytes, as attested by an accelerated GVHD after allogeneic hematopoietic stem cell transplantation (HSCT) in mice. We thus propose a clinical trial to test whether Treg-depleted donor lymphocytes infusion (dDLI) could induce an improved graft-versus-tumor (GVT) effect in patients refractory to standard DLI (stdDLI) for treatment of relapse after HSCT.

dDLI is administered after failure of 1 or several previous stdDLI of at least 107 CD3+ cells/kg, defined after a minimal follow-up of 2 months after the last injection. The absence of previous clinical manifestations of GVHD is required to be included. To prepare dDLI, CD25+ Treg are depleted from donor leukaphereses using anti-CD25 magnetic microbeads and a CliniMACS device (MYLTENYI). In order to evidence the potential effect of dDLI, the dDLI cell dose is adjusted to be below or equal to the maximal cell dose previously received in stdDLI. No comparison is planned in the analysis.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• Hematological malignancy except chronic myeloid leukaemia.

• Previous allogeneic hematopoietic stem cell transplantation.

• Relapse diagnosed at the molecular, cytogenetic, or cytological level.

• Failure of a previous stdILD or inclusion in first intention if progressive disease.

• Age > 18 years and < 70 years at the time of inclusion.

• Performance status considered on the score ECOG < 2.

• Life expectation 1-month-old superior.

• Signed written informed consent.

• Negative HCG in the 7 days preceding the inclusion for women in age of procreation.

• Membership of the French national insurance.

Exclusion Criteria:

• Chronic myeloid leukemia

• Grade >II acute GVHD or chronic extensive GVHD at the time of inclusion.

• Patient receiving an immunosuppressive treatment for GVHD treatment at the time of inclusion.

• Dysfunction of liver (ALAT/ASAT > 5 N, or bilirubin > 50 µM), or of the renal function (creatinine clearance < 30 ml / min).

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Relapse

Intervention

Procedure:
• donor lymphocyte infusion
regulatory T cells depletion

Locations

Country	Name	City	State
France	Hopital Henri Mondor	Créteil

Sponsors (3)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Pierre and Marie Curie University, Université Paris XII

Country where clinical trial is conducted

France, 

References & Publications (1)

Maury S, Lemoine FM, Hicheri Y, Rosenzwajg M, Badoual C, Cheraï M, Beaumont JL, Azar N, Dhedin N, Sirvent A, Buzyn A, Rubio MT, Vigouroux S, Montagne O, Bories D, Roudot-Thoraval F, Vernant JP, Cordonnier C, Klatzmann D, Cohen JL. CD4+CD25+ regulatory T c — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%.		4 weeks after dDLI	Yes
Secondary	The incidence of GVHD of any grade after dDLI		during the 12 months	No
Secondary	The anti-tumoral efficiency of dDLI to treat the relapse of the hematological malignancy		during the 12 months	No
Secondary	The survival and the survival without disease after dDLI		during the 12 months	Yes