Clinical trial NCT03079089: Sequential Conditioning in Haploidentical Transplantation for Hematopoietic Stem Cells in Patients With Relapsed or Refractory Lymphoid Hematological Disorders
Official title: Sequential Chemotherapy Prior Conditioning Reduced Intensity: Study Routine Care in Haploidentical Allogeneic Hematopoietic Stem Cells in Patients With Relapsed or Refractory Lymphoid Hematological Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Refractory or Relapsed Lymphoid Haemopathy
Keywords: Allogenic cell stem transplant
Sequential chemotherapy
Haploidentical transplant
Lead sponsor: Association for Training, Education, and Research in Hematology, Immunology, and Transplantation
Sponsor class: OTHER
First posted: 2017-03-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Patients with refractory or relaps lymphoid hematological disorders
Primary purpose: OTHER

Brief summary: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment option with a significant chance of healing in lymphoid hematological refractory or multiple relapses after chemotherapy. However, all patients with an indication of allo-HSC can not benefit because of two limitations: the toxicity of the treatment and graft shortage available.

For patients refractory or in relapses with an indication of allo-HSC, used the combinaison of an SET followed by the reduced-intensity allo-HSC (RIC) has shown some interesting results.

A post-transplant immune modulation with prophylactic injections of donor lymphocytes (PDLI) showed its effectiveness to decrease the risk of relapse while having a lower toxicity than chemotherapy


Eligibility criteria: Inclusion Criteria:

* Patients with an indication of allo-HSC for a lymphoid hematological malignancy like Hodgkin's lymphoma, non hodgkin's lymphoma b cell (mantle follicular, diffuse large cells, marginal zone,MALT) or T (peripheral T whithout specificity, anaplasic, angio-immunoblastic, natural killer cells, gamma / delta T cells, Sezary's syndrome, primitive cutaneous T), prolymphocytic leukemia, chronic lymphocytic leukemia, waldenström's disease and for which a therapeutic strategie combining a sequential chemotherapy followed by the reduced-intensity conditioning(SET RIC + PDLI) is decided
* Patients at least in partial response (standard criteria) after a rescue treatment the day of evaluation at 1 month before the conditioning
* Advanced age ≥ 18 to \<60 years
* Cardiac ejection fraction of the left ventricle ≥ 45%
* Lung function - free diffusion capacity for carbon monoxide ≥ 50% of predicted value
* Creatinine clearance ≥ 50 ml / min depending on the CKD-EPI formula
* Availability of an HLA haploidentical donor in the family
* Collection of non-opposition

Exclusion Criteria:

* Invasion of uncontrolled CNS
* Availability of an HLA identical family donor who agreed to donate hematopoietic stem cells OR non-related donor HLA-compatible 10/10 on HLA-A alleles, B, C, and DRB1 DQB1 available and ready to give in 4 weeks to make a decision allograft
* Presence in the patient HLA-specific antibodies directed against an antigen HLA haploidentical donor family
* Karnofsky score \<70%
* Patient HIV positive
* Hepatitis B or C or chronic active
* Uncontrolled infection at the time of start packing
* Contraindication to the use of treatments provided by the protocol
* Previous history of allo-HSC
* No beneficiary of a social security scheme.
* life expentancy estimated less than 1 month by investigator

Primary outcomes:
measure: Overall survival (OS)
timeFrame: 2 years after transplantation
Secondary outcomes:
measure: Partial or complete remission rate by standard criteria relapse incidence and death related to the disease and free survival
timeFrame: 90 days and then 6, 12 and 24 months after transplantation
measure: Cumulative incidence of death not related to relapse
timeFrame: 90 days and then 12 and 24 months after transplantation
measure: Cumulative incidence of acute and chronic graft against host disease (GVHD)
timeFrame: 100 days and then 12 and 24 months after transplantation
measure: Number of patients for whom PDLI was possible and number PDLI / patient ; incidence, severity and treatment of possible secondary GVHD in these patients
timeFrame: 2 years after transplantation
measure: Immune reconstitution post-transplantation in the peripheral blood
timeFrame: 30, 90 and 180 days after transplantation
measure: Tolerance of this therapeutic strategy
timeFrame: 90 days and the 6, 12 and 24 month after transplantation
Other outcomes:
Locations:
city: Paris
country: France
facility: Service d'hématologie clinique Hôpital Saint Antoine
Study officials:
References: