Studyof Allogeneic Hematopoietic Stem Cell Transplantation From One Haplotype Mismatch Related Donor or From an Unrelated Donor in Elderly Patients
Condition: Hematologic Neoplasms
MeSH terms: Hematologic Neoplasms
Study type: Interventional
Phase: Phase 3

Summary: 
      Allogeneic (Allo) hematopoietic stem cell transplantation (HSCT) is a recognized curative
      procedure for hematological malignancies. It is now well known that this property is related
      to the graft-versus-tumor (GVT) effect developed from the immunocompetent cells contained in
      or generating from the donor graft. For years, however, and despite this unique antitumoral
      activity, Allo-HSCT has been restricted to a limited number of patients due to two major
      limitations: the toxicity of the procedure and the absence of a donor for every single
      patients. More recently the stage has dramatically changed with respect to these two
      restraints. Over the last decade, many studies have established the feasibility of Allo-HSCT
      in older patients but the availability of MRD is even less frequent in elderlies, likely
      related to medical contraindication for graft donation or sibling deaths. UD are routinely
      used but associated with a high incidence of GVHD. As compared to younger populations,
      unrelated cord-blood HSCT is seldom performed in this population and numbers decrease with
      age due to the feared risk of supposed increased lethal infectious complications related to
      the effect of the delayed immune reconstitution in elderlies. Thus the need for alternative
      donors allowing for a safe and efficient transplantation is still unmet. In consequence,
      overall, despite the fact that Allo-HSCT feasibility has been established in the oldest
      patients, all these lacks contribute eventually to maintain a low rate of allo-HSCT performed
      in a population with the higher incidence of hematologic malignancies that usually present
      with the poorest prognosis.

      Thus it is critical developing innovative efficient therapeutic strategies answering this
      unmet-medical need. In this perspective, Haplo-HSCT could represent a part of the answer in
      this aged population. It offers the potential advantage to offer a rapid donor determination
      for virtually every single patient. In addition, our data suggest that in elderlies
      haplo-HSCT using T-repleted graft, RIC and PT-HDCy presents low NRM and retains an antitumor
      effect despite low GVHD incidences. They also suggest that haplo-HSCT may conduct to better
      outcome than URD-HSCT as an alternative to MRD-HSCT. It may also be associated with lower
      costs (no graft purchase and low post-transplant complications rate) and better QOL likely
      related to low cGVHD-rate. In addition the conduct of such trial at a time when the diffusion
      of the strategy in this population is just starting is really crucial before widespread
      uncontrolled dissemination.

      The investigators propose to address this question by prospectively comparing these 2
      strategies in elderly patients without MRD, in terms of efficacy, safety and including the
      prospective evaluation study of quality-of-life (QOL). They will conduct a national,
      multicenter, open-label, comparative, randomized phase III trial in patients with
      hematological malignancies justifying an allo-HSCT from an alternative donor when a MRD has
      not been identified.

      When MRD search is recognized to be a failure, patients will be included in the clinical
      trial after informed consent and randomized in the two strategies based on donor search:

        -  Reference group: Unrelated Donor group

        -  Investigational group: Haplo Donor Group

      Investigators will use a composite end-point embracing the three main causes of failure:
      death, relapse and severe cGVHD (as a surrogate endpoint for QOL). We will analyze the HSCT
      usual objectives as GHVD, NRM, relapse and survival. A specific study of patients' health
      related quality of life will also be conducted using the FACT-BMT questionnaire. In addition,
      the success of the two strategies in term of transplant completion (donor determination,
      transplant realization and time to do so) will be compared.
    


Intervention name(s): Allogeneic (Allo) hematopoietic stem cell transplantation
Intervention type(s): Biological
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment