Eradication of Residual Disease by Preemptive Immunointervention After Allogeneic Hematopoietic Stem Cells Transplantation in Chronic Lymphocytic Leukemia

NCT01849939 | Unknown Phase 2

• 2 other identifiers: CHU-01502011-A00906-35
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

Usually Chronic lymphocytic leukemia (CLL) is a disease of the elderly patients. However, the diagnosis in young patients become more frequently with poor prognosis. The identification of new prognostic factors permits early determination of the high risk population and provide them the therapeutic intensification. Allogeneic transplantation of hematopoietic stem cells transplantation (AHSCT) allows to long-term remission and in some cases complete and definitive eradication of the disease. After chemotherapy or antibodies, the Minimal Residual Disease (MRD) negativity is associated with better disease-free survival. MRD negativity occurs in some patients with the appearance of GVHD, stopping the immunosuppression or after donor lymphocyte injection (DLI). The negativity of MRD in the first year post-transplant is correlated with better progression-free survival or overall survival (Dreger 2010, Farina 2009, Caballero 2005, Algrin, 2011). So, MRD negativity may be an objective after AHSCT. The aim of this prospective study is to evaluate a standardized preemptive immunointervention of post-allograft immunosuppressive therapy modulation and DLI administration according to MRD level. The objective is to obtain MRD negativity at 12 months after AHSCT.

Conditions

Chronic Lymphocytic Leukemia; Lymphocytic Lymphoma

Keywords

Allogeneic transplantation of hematopoietic stem cells transplantation; Chronic Lymphocytic Leukemia; Donor Lymphocyte Injection; Preemptive immunointervention

Outcome Measures

Primary Outcomes (1)

• MRD(Minimal Residual Disease) negativity level

  12 months after AHSCT(Allogenic Transplantation of Hematopoietic Stem Cells Transplantation)

Secondary Outcomes (6)

• Incidence of relapses progression

  at 12 months

• Incidence of toxic deaths

  at 12 months

• Incidence of GVHD (acute and chronic)

  at 12 months

• Survival (progression free survival, overall survival, survival without treatment)

  at 12 months

• Post-transplant chimerism (total blood and lymphoid T lymphocyte populations)

  baseline; 1, 2, 3, 6 and 12 months

Study Arms (1)

Fludarabin

EXPERIMENTAL

Drug: Fludarabin (post-allograft immunosuppressive therapy modulation and DLI Mononuclear cells from allogenic blood)

Interventions

Fludarabin (post-allograft immunosuppressive therapy modulation and DLI Mononuclear cells from allogenic blood) DRUG

Fludarabin

Eligibility Criteria

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

You may qualify if:

• Patients with CLL (Matutes score 4 or 5) stages A, B, C with evolution criteria according IWCLL 2008 or lymphocytic lymphoma with severity criteria (EBMT criteria) which indicated allograft (deletion 17p) and requiring treatment
• Age: 18-70 years
• At least one of the following criteria of poor prognosis (EBMT recommendations - Dreger 2007)
• No response or relapse within 12 months of treatment with purine analogues (including "fludarabine refractory" i.e patients in response \<PR and / or relapse within 6 months after at least 2 courses of Fludurabine)
• relapse within 24 months after combination therapy including purine analogs or autograft, with indication of new start of treatment
• Mutation/deletion 17p13 (p53) with indication for treatment
• Partial response (PR) or complete response (CR) at the last treatment (IWCLL 2008)
• Residual mass \<5 cm (clinical and CT scan)
• Identical intrafamilial donor HLA (or with a mismatch) or in the absence of family donor, an unrelated donor 10/10 for HLA A, B, C, DR, DQ and is committed to giving DLI (see consent form donor)
• Sorror score comorbidity: ≤ 2
• Written informed consent
• Member or beneficiary of a social security system

You may not qualify if:

• Richter Syndrome
• Usual contraindications for realisation of allogeneic transplantation including
• Uncontrolled bacterial, viral or fungal infection
• Pregnancy or lactating women
• Cardiac contraindication : Cardiac ejection fraction \<50%
• Pulmonary contraindication : DLCO \<50%
• Renal contraindication : Creatininine clearance \<30 ml / min
• Hepatic contraindication : AST and / or ALT and / or total bilirubine\> 2 N except Gilbert disease or localisation specific LLC
• HIV positivity
• Cancer evolution or de novo occurred in the previous 5 years except basal cell cancer skin or carcinoma in situ of the cervix of uterus
• Affection psychiatric disease

Sponsors & Collaborators

• University Hospital, Clermont-Ferrand: lead
• Pierre Fabre Laboratories: collaborator

Study Sites (1)

CHU Clermont-Ferrand

Clermont-Ferrand, 63003, France

RECRUITING

MeSH Terms

Conditions

Leukemia, Lymphocytic, Chronic, B-Cell

Condition Hierarchy (Ancestors)

Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Olivier Tournilhac

  University Hospital, Clermont-Ferrand

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Patrick LACARIN

CONTACT

04 73 75 11 95; placarin@chu-clermontferrand.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2013
• First Posted: May 9, 2013
• Study Start: September 1, 2012
• Primary Completion: September 1, 2017
• Study Completion: September 1, 2017
• Last Updated: May 9, 2013

Record last verified: 2013-05

Locations

FR (1)