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

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ClinicalTrials.gov Identifier: NCT01849939
Recruitment Status : Unknown
Verified May 2013 by University Hospital, Clermont-Ferrand.
Recruitment status was:  Recruiting
First Posted : May 9, 2013
Last Update Posted : May 9, 2013
Sponsor:
Collaborator:
Pierre Fabre Laboratories
Information provided by (Responsible Party):
University Hospital, Clermont-Ferrand

Tracking Information
First Submitted Date  ICMJE March 12, 2013
First Posted Date  ICMJE May 9, 2013
Last Update Posted Date May 9, 2013
Study Start Date  ICMJE September 2012
Estimated Primary Completion Date September 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 8, 2013)
MRD(Minimal Residual Disease) negativity level [ Time Frame: 12 months after AHSCT(Allogenic Transplantation of Hematopoietic Stem Cells Transplantation) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History No Changes Posted
Current Secondary Outcome Measures  ICMJE
 (submitted: May 8, 2013)
  • Incidence of relapses progression [ Time Frame: at 12 months ]
  • Incidence of toxic deaths [ Time Frame: at 12 months ]
  • Incidence of GVHD (acute and chronic) [ Time Frame: at 12 months ]
  • Survival (progression free survival, overall survival, survival without treatment) [ Time Frame: at 12 months ]
  • Post-transplant chimerism (total blood and lymphoid T lymphocyte populations) [ Time Frame: baseline; 1, 2, 3, 6 and 12 months ]
  • Incidence of infectious complications and severity [ Time Frame: at 12 months ]
    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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Eradication of Residual Disease by Preemptive Immunointervention After Allogeneic Hematopoietic Stem Cells Transplantation in Chronic Lymphocytic Leukemia
Official Title  ICMJE Reduced Intensity Conditioning Allogeneic Transplantation for CLL With Preemptive MDR Management (ICLL 03 RICAC-PMM)
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
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Lymphocytic Leukemia
  • Lymphocytic Lymphoma
Intervention  ICMJE Drug: Fludarabin (post-allograft immunosuppressive therapy modulation and DLI Mononuclear cells from allogenic blood)
Study Arms  ICMJE Experimental: Fludarabin
Intervention: Drug: Fludarabin (post-allograft immunosuppressive therapy modulation and DLI Mononuclear cells from allogenic blood)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Unknown status
Estimated Enrollment  ICMJE
 (submitted: May 8, 2013)
43
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2017
Estimated Primary Completion Date September 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 70 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE France
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01849939
Other Study ID Numbers  ICMJE CHU-0150
2011-A00906-35
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University Hospital, Clermont-Ferrand
Study Sponsor  ICMJE University Hospital, Clermont-Ferrand
Collaborators  ICMJE Pierre Fabre Laboratories
Investigators  ICMJE
Principal Investigator: Olivier Tournilhac University Hospital, Clermont-Ferrand
PRS Account University Hospital, Clermont-Ferrand
Verification Date May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP