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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

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.

Condition or disease Intervention/treatment Phase
Chronic Lymphocytic Leukemia Lymphocytic Lymphoma Drug: Fludarabin (post-allograft immunosuppressive therapy modulation and DLI Mononuclear cells from allogenic blood) Phase 2

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 43 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reduced Intensity Conditioning Allogeneic Transplantation for CLL With Preemptive MDR Management (ICLL 03 RICAC-PMM)
Study Start Date : September 2012
Estimated Primary Completion Date : September 2017
Estimated Study Completion Date : September 2017


Arm Intervention/treatment
Experimental: Fludarabin Drug: Fludarabin (post-allograft immunosuppressive therapy modulation and DLI Mononuclear cells from allogenic blood)



Primary Outcome Measures :
  1. MRD(Minimal Residual Disease) negativity level [ Time Frame: 12 months after AHSCT(Allogenic Transplantation of Hematopoietic Stem Cells Transplantation) ]

Secondary Outcome Measures :
  1. Incidence of relapses progression [ Time Frame: at 12 months ]
  2. Incidence of toxic deaths [ Time Frame: at 12 months ]
  3. Incidence of GVHD (acute and chronic) [ Time Frame: at 12 months ]
  4. Survival (progression free survival, overall survival, survival without treatment) [ Time Frame: at 12 months ]
  5. Post-transplant chimerism (total blood and lymphoid T lymphocyte populations) [ Time Frame: baseline; 1, 2, 3, 6 and 12 months ]
  6. 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



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

    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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01849939


Contacts
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Contact: Patrick LACARIN 04 73 75 11 95 placarin@chu-clermontferrand.fr

Locations
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France
CHU Clermont-Ferrand Recruiting
Clermont-Ferrand, France, 63003
Contact: Patrick LACARIN    04 73 75 11 95    placarin@chu-clermontferrand.fr   
Sponsors and Collaborators
University Hospital, Clermont-Ferrand
Pierre Fabre Laboratories
Investigators
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Principal Investigator: Olivier Tournilhac University Hospital, Clermont-Ferrand

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Responsible Party: University Hospital, Clermont-Ferrand
ClinicalTrials.gov Identifier: NCT01849939     History of Changes
Other Study ID Numbers: CHU-0150
2011-A00906-35
First Posted: May 9, 2013    Key Record Dates
Last Update Posted: May 9, 2013
Last Verified: May 2013
Keywords provided by University Hospital, Clermont-Ferrand:
Allogeneic transplantation of hematopoietic stem cells transplantation
Chronic Lymphocytic Leukemia
Donor Lymphocyte Injection
Preemptive immunointervention
Additional relevant MeSH terms:
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Leukemia
Leukemia, Lymphoid
Leukemia, Lymphocytic, Chronic, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Leukemia, B-Cell
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs