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Studyof Allogeneic Hematopoietic Stem Cell Transplantation From One Haplotype Mismatch Related Donor or From an Unrelated Donor in Elderly Patients

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ClinicalTrials.gov Identifier: NCT02623309
Recruitment Status : Recruiting
First Posted : December 7, 2015
Last Update Posted : March 28, 2017
Sponsor:
Information provided by (Responsible Party):
Institut Paoli-Calmettes

Brief 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.


Condition or disease Intervention/treatment Phase
Hematologic Neoplasms Procedure: Allogeneic (Allo) hematopoietic stem cell transplantation Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 108 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : February 2016
Estimated Primary Completion Date : February 2019
Estimated Study Completion Date : February 2021

Arm Intervention/treatment
Experimental: HAPLO graft

Conditioning regimen

  • Fludarabin : 30 mg/m2/day for 4 days: from D-5 à J-2.
  • Busulfan IV : 130 mg/m2/day for 2 days : drom D-4 to D-3. + 1 day of Thiotepa : 5mg/kg at D-6.

Prophylaxis regimen for GVHD

  • F CSA and MMF (starting day +5)
  • Additional immunosuppression: PT-HDCy (50 mg/kg/day) on days +3 and +4

Hematopoietic Stem Cell Graft PBSC graft will be preferred for a minimal targeted cell dose of 4 x 106 CD34+cells/kg GCSF (Neupogen ®) during 4 to 5 days (D-4 to D-1): SC 10 µg/kg/d.

Procedure: Allogeneic (Allo) hematopoietic stem cell transplantation
Active Comparator: MUD graft

Conditioning regimen

  • Fludarabin : 30 mg/m2/day for 5 days: from D-6 to D-2.
  • Busulfan IV : 130 mg/m2/day for 2 days: from D-4 to D-3.

Prophylaxis regimen for GVHD

  • CSA and MMF will be used from day -1 after UD
  • Additional immunosuppression: Rabbit ATG (2.5 mg/kg/day) on days -3 and -2

Hematopoietic Stem Cell Graft PBSC graft will be preferred for a minimal targeted cell dose of 4 x 106 CD34+cells/kg

Procedure: Allogeneic (Allo) hematopoietic stem cell transplantation



Primary Outcome Measures :
  1. Event-free survival with death, relapse or occurrence of severe cGVHD as event whatever occurs first [ Time Frame: 5 years ]

Secondary Outcome Measures :
  1. Engraftment: time to reach 0.5 x 109/l ANC, 20 x 109/l platelets and full donor lymphoid chimerism [ Time Frame: 5 years ]
  2. Acute and chronic GVHD cumulative incidences [ Time Frame: 5 years ]
  3. Non-relapse mortality cumulative incidence [ Time Frame: 5 years ]
  4. Relapse incidence [ Time Frame: 5 years ]
  5. Probabilities of overall survival and progression-free survival [ Time Frame: 5 years ]
  6. Evaluation of HRQL including patients who relapse [ Time Frame: 5 years ]
  7. Evaluation of procedure costs from beginning of search until death or two-year follow-up [ Time Frame: 5 years ]


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Ages Eligible for Study:   55 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients aged of 55 years or up to 70 years.
  • Patients with hematological malignancy
  • Patients without a matched related donor
  • Patients eligible for an allogeneic HSCT from an alternative donor
  • Able to comply with the protocol
  • Written informed consent
  • Affiliation to Social Security System

Exclusion Criteria:

  • Clinical or biological contraindication to allogeneic HSCT
  • Other evolutive cancer
  • Positive serology for HIV, hepatitis B or chronic active hepatitis C
  • Pregnant or breast-feeding women.
  • Emergency
  • Patient considered socially or psychologically unable to comply with the treatment and the required medical follow-up.

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): NCT02623309


Contacts
Contact: Dominique GENRE, MD +33 4 91 22 37 78 drci.up@ipc.unicancer.fr
Contact: Jihane PAKRADOUNI, PharmD,PhD +33 4 91 22 37 78 drci.up@ipc.unicancer.fr

Locations
France
CHU Amiens Recruiting
Amiens, France
Contact: Amandine Charbonnier, MD       Charbonnier.Amandine@chuamiens.fr   
Principal Investigator: Amandine Charbonnier, MD         
CHU Besançon Recruiting
Besançon, France
Contact: Ana Berceanu, MD       aberceanu@chu-besancon.fr   
Principal Investigator: Ana Berceanu, MD         
CHU Estaing/Clermont-ferrand Recruiting
Clermont-ferrand, France
Contact: Eric Hermet, MD         
Principal Investigator: Eric Hermet, MD         
Principal Investigator: Jacques-Olivier Bay, MD         
CHU Albert Michallon Recruiting
Grenoble, France
Contact: Claude-Eric Bulabois, MD         
Principal Investigator: Claude-Eric Bulabois, MD         
CHU Limoges Recruiting
Limoges, France
Contact: Pascal Turlure, MD       Pascal.turlure@chu-limoges.fr   
Principal Investigator: Pascal Turlure, MD         
Institut Paoli Calmettes Recruiting
Marseille, France, 13009
Contact: Dominique GENRE, MD    33491223778    drci.up@ipc.unicancer.fr   
Contact: Jihane PAKRADOUNI, PharmD, PhD    33491223778    drci.up@ipc.unicancer.fr   
Principal Investigator: Didier BLAISE, MD PhD         
CHRU Montpellier Recruiting
Montpellier, France
Contact: Patrice CEBALLOS, MD       p-ceballos@chu-montpellier.fr   
Principal Investigator: Patrice CEBALLOS, MD         
Principal Investigator: Nathalie Fegueux, MD         
CHU Nantes Recruiting
Nantes, France
Contact: Patrice Chevallier, MD       Patrice.chevallier@chunantes.fr   
Principal Investigator: Patrice Chevallier, MD         
Hôpital Necker Recruiting
Paris, France
Contact: Felipe Suarez, MD       felipe.suarez@nck.aphp.fr   
Principal Investigator: Felipe Suarez         
Hôpital Saint Antoine Recruiting
Paris, France
Contact: Mohamad Mohty, MD       mohamad.mohty@inserm.fr   
Principal Investigator: Mohamad Mohty, MD         
Hôpital Saint Louis Recruiting
Paris, France
Contact: Regis Peffault de latour, MD       regis.peffaultdelatour@sls.aph   
Principal Investigator: Regis Peffault de latour, MD         
Hôpital Haut Leveque Recruiting
Pessac, France
Contact: Reza Tabrizi, MD       reza.tabrizi@chu-bordeaux.fr   
Principal Investigator: Reza Tabrizi, MD         
Institut de Cancérologie Lucien Neuwirth Recruiting
Saint Priest en Jarez, France
Contact: Jérôme CORNILLON, MD       Jerome.cornillon@icloire.fr   
Principal Investigator: Jérôme CORNILLON, MD         
IUCT Recruiting
Toulouse, France
Contact: Anne Huynh, MD       Huynh.Anne@iuct-oncopole.fr   
Principal Investigator: Anne Huynh, MD         
Sponsors and Collaborators
Institut Paoli-Calmettes
Investigators
Principal Investigator: Didier Blaise, MD Institut Paoli-Calmettes

Responsible Party: Institut Paoli-Calmettes
ClinicalTrials.gov Identifier: NCT02623309     History of Changes
Other Study ID Numbers: HAPLOMUDELDERLY-IPC 2015-004
First Posted: December 7, 2015    Key Record Dates
Last Update Posted: March 28, 2017
Last Verified: March 2017

Additional relevant MeSH terms:
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Hematologic Diseases