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

NCT00987987 | Completed Phase 1

• 1 other identifier: P040441
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Hematologic Neoplasms; Relapse

Keywords

hematological malignancy; allogeneic hematopoietic stem cell transplantation; donor lymphocyte infusion; antitumor immunotherapy; graft-versus-tumor effect; regulatory T cells; adult

Outcome Measures

Primary Outcomes (1)

• Incidence of "severe" GHVD (grade >II) following dDLI should be inferior to 40%.

  4 weeks after dDLI

Secondary Outcomes (3)

• The incidence of GVHD of any grade after dDLI

  during the 12 months

• The anti-tumoral efficiency of dDLI to treat the relapse of the hematological malignancy

  during the 12 months

• The survival and the survival without disease after dDLI

  during the 12 months

Study Arms (1)

1

EXPERIMENTAL

1

Procedure: donor lymphocyte infusion

Interventions

donor lymphocyte infusion PROCEDURE

regulatory T cells depletion

Also known as: regulatory T cells depletion

1

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Hematological malignancy except chronic myeloid leukaemia.
• Previous allogeneic hematopoietic stem cell transplantation.
• Relapse diagnosed at the molecular, cytogenetic, or cytological level.
• Performance status considered on the score ECOG \< 2.
• Life expectation 1-month-old superior.
• Signed written informed consent.
• Membership of the French national insurance.

You may not qualify if:

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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• Université Paris XII: collaborator
• Pierre and Marie Curie University: collaborator

Study Sites (1)

Hopital Henri Mondor

Créteil, 94000, France

Location

Related Publications (1)

• Maury S, Lemoine FM, Hicheri Y, Rosenzwajg M, Badoual C, Cherai 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 cell depletion improves the graft-versus-tumor effect of donor lymphocytes after allogeneic hematopoietic stem cell transplantation. Sci Transl Med. 2010 Jul 21;2(41):41ra52. doi: 10.1126/scitranslmed.3001302.

  PMID: 20650872 RESULT

MeSH Terms

Conditions

Hematologic Neoplasms; Recurrence

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Sébastien Maury, MD Ph

  Assistance Publique - Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 30, 2009
• First Posted: October 1, 2009
• Study Start: December 1, 2005
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: January 24, 2011

Record last verified: 2009-09

Locations

FR (1)