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

Primary Purpose

Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma

Status
Unknown status
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Fludarabin (post-allograft immunosuppressive therapy modulation and DLI Mononuclear cells from allogenic blood)
Sponsored by
University Hospital, Clermont-Ferrand
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia focused on measuring Allogeneic transplantation of hematopoietic stem cells transplantation, Chronic Lymphocytic Leukemia, Donor Lymphocyte Injection, Preemptive immunointervention

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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)

    1. 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)
    2. relapse within 24 months after combination therapy including purine analogs or autograft, with indication of new start of treatment
    3. 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

Exclusion Criteria:

  • 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

Sites / Locations

  • CHU Clermont-FerrandRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Fludarabin

Arm Description

Outcomes

Primary Outcome Measures

MRD(Minimal Residual Disease) negativity level

Secondary Outcome Measures

Incidence of relapses progression
Incidence of toxic deaths
Incidence of GVHD (acute and chronic)
Survival (progression free survival, overall survival, survival without treatment)
Post-transplant chimerism (total blood and lymphoid T lymphocyte populations)
Incidence of infectious complications and severity
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

Full Information

First Posted
March 12, 2013
Last Updated
May 8, 2013
Sponsor
University Hospital, Clermont-Ferrand
Collaborators
Pierre Fabre Laboratories
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1. Study Identification

Unique Protocol Identification Number
NCT01849939
Brief Title
Eradication of Residual Disease by Preemptive Immunointervention After Allogeneic Hematopoietic Stem Cells Transplantation in Chronic Lymphocytic Leukemia
Acronym
RICAC
Official Title
Reduced Intensity Conditioning Allogeneic Transplantation for CLL With Preemptive MDR Management (ICLL 03 RICAC-PMM)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2013
Overall Recruitment Status
Unknown status
Study Start Date
September 2012 (undefined)
Primary Completion Date
September 2017 (Anticipated)
Study Completion Date
September 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Clermont-Ferrand
Collaborators
Pierre Fabre Laboratories

4. Oversight

5. Study Description

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.
Detailed Description
Patients will receive AHSCT with Fludarabine-Busulfan based conditioning : Fludarabine : 30 mg/m2/day - from Day-6 to Day-2 Busulfan IV : 3.2 mg/kg/day - on Day-5 and Day-4 ATG (Anti-thymocyte Globulin) : 2.5 mg/kg/day on Day-2 and Day-1 Preemptive immunointervention post AHSCT consists in reduce immunosuppressive treatment more or less associated with DLI according to : the presence or absence of severe Graft versus host disease (GVHD) (acute grade 2 and / or chronic) the presence or absence of a response on criteria of response IWCLL Getting or not a blood MRD negative (<-10 ^ -4) evaluated by flow cytometry

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma
Keywords
Allogeneic transplantation of hematopoietic stem cells transplantation, Chronic Lymphocytic Leukemia, Donor Lymphocyte Injection, Preemptive immunointervention

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
43 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Fludarabin
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Fludarabin (post-allograft immunosuppressive therapy modulation and DLI Mononuclear cells from allogenic blood)
Primary Outcome Measure Information:
Title
MRD(Minimal Residual Disease) negativity level
Time Frame
12 months after AHSCT(Allogenic Transplantation of Hematopoietic Stem Cells Transplantation)
Secondary Outcome Measure Information:
Title
Incidence of relapses progression
Time Frame
at 12 months
Title
Incidence of toxic deaths
Time Frame
at 12 months
Title
Incidence of GVHD (acute and chronic)
Time Frame
at 12 months
Title
Survival (progression free survival, overall survival, survival without treatment)
Time Frame
at 12 months
Title
Post-transplant chimerism (total blood and lymphoid T lymphocyte populations)
Time Frame
baseline; 1, 2, 3, 6 and 12 months
Title
Incidence of infectious complications and severity
Description
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
Time Frame
at 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Patrick LACARIN
Phone
04 73 75 11 95
Email
placarin@chu-clermontferrand.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Olivier Tournilhac
Organizational Affiliation
University Hospital, Clermont-Ferrand
Official's Role
Principal Investigator
Facility Information:
Facility Name
CHU Clermont-Ferrand
City
Clermont-Ferrand
ZIP/Postal Code
63003
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patrick LACARIN
Phone
04 73 75 11 95
Email
placarin@chu-clermontferrand.fr

12. IPD Sharing Statement

Learn more about this trial

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

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