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Sequential Conditioning in Haploidentical Transplantation for Refractory Acute Myeloid Leukemia (SET-HAPLO)

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ClinicalTrials.gov Identifier: NCT03035422
Recruitment Status : Recruiting
First Posted : January 30, 2017
Last Update Posted : January 30, 2019
Sponsor:
Information provided by (Responsible Party):
Association for Training, Education, and Research in Hematology, Immunology, and Transplantation

Brief Summary:
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment option with a significant chance of healing in acute myeloid leukemia (AML) or refractory 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.

Condition or disease Intervention/treatment Phase
Refractory Acute Myeloid Leukemia Drug: Sequential Packaging (SET) Drug: Transfusion graft Drug: Prevention of GVHD Drug: Care supports Drug: Lymphocyte injection of prophylactic donor (PDLI) Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Sequential Chemotherapy Prior to Reduced Intensity Conditioning: Interventional Study in Haploidentical Hematopoietic Stem Cells Transplantation for Patients With Refractory Acute Myeloid Leukemia
Actual Study Start Date : January 15, 2018
Estimated Primary Completion Date : January 2021
Estimated Study Completion Date : January 2021


Arm Intervention/treatment
Patients with primary refractory acute myeloid leukemia
Patients with primary refractory acute myeloid leukemia
Drug: Sequential Packaging (SET)

Sequential chemotherapy:

  • Thiotepa 5 mg / kg / day for 1 day (D-13)
  • Cyclophosphamide 400 mg / m² / day for 4 days (J-12 to J-9)
  • Etoposide 100 mg / m² / day for 4 days (J-12 to J-9) Repos days J-8 and J-6 Reduced-intensity conditioning (RIC)
  • Fludarabine 30 mg / m² / day for 5 days (J-5 to D-1)
  • Busulfan IV 3.2 mg / kg / day for 2 days (J-5 and J-4)
  • Anti-lymphocyte serum (Thymoglobuline) 2.5 mg / kg / day for 2 days (J-3 and J-2)

Drug: Transfusion graft
Graft of peripheral stem cells is preferred at D0

Drug: Prevention of GVHD
  • Cyclophosphamide 50mg / kg / day on days D + 3 and D + 5
  • Cyclosporine A (CSA; 3 mg / kg / day IV from D + 6)
  • Mycophenolate mofetil (MMF; 30 mg / kg / day, maximum x2 1g / day from day J + 6)

Drug: Care supports
According to the protocols of each center

Drug: Lymphocyte injection of prophylactic donor (PDLI)

According to the protocols of each center. In the absence of clinical indication against-disease (GVHD), phasing MMF between days D + 35 and D + 56, then phasing APF between D + 62 and D + 90

- PDLI: 3 injections from the D + 120 patients who discontinued immunosuppressive therapy for ≥ 1 month and having no active GVHD or history of acute GVHD grade> II





Primary Outcome Measures :
  1. Overall survival (OS) [ Time Frame: 2 years after transplantation ]

    The aim is to describe the efficacy of the combination of a SET followed by haploidentical transplant with post-transplant immune modulation by pDLI in patients with AML.

    The main objective is to assess overall survival at 2 years in these patients.



Secondary Outcome Measures :
  1. Partial or complete remission rate by standard criteria Relapse incidence and death related to the disease [ Time Frame: 90 days and then 6, 12 and 24 months after transplantation ]
    To evaluate the efficacy of this therapeutic strategy in terms of remission of disease, incidence of relapse

  2. Cumulative incidence of death not related to relapse [ Time Frame: 90 days and then 12 and 24 months after transplantation ]
    Assess not related to relapse mortality

  3. Cumulative incidence of acute and chronic graft against host disease (GVHD) [ Time Frame: 100 days and then 12 and 24 months after transplantation ]
    To evaluate the incidence of acute and chronic graft against host disease (GVHD)

  4. Number of patients for whom pDLI was possible. [ Time Frame: 2 years after transplantation ]
    Assess the feasibility of prophylactic injections of donor lymphocytes (pDLI)

  5. Study of immune reconstitution post-transplant in the peripheral blood will be used:CD4 lymphocyte levels, CD8, T regulators, Natural Killer cells and B cells [ Time Frame: 90 days and then 6, 12 and 24 months after transplantation ]
    Study the post-transplant immune reconstitution

  6. Leukemia free survival [ Time Frame: 90 days and then 6, 12 and 24 months after transplantation ]
    Relapse-free survival

  7. Number of pDLI / patient; incidence, severity and treatment of possible secondary GVHD in these patients [ Time Frame: 90 days and then 6, 12 and 24 months after transplantation ]
    Assess the feasibility of prophylactic injections of donor lymphocytes (pDLI)



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Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients with a confirmed diagnosis of acute myeloid leukemia after primary induction treatment failure (persistent leukemia after 2 cycles of induction chemotherapy)
  • Patient 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:

  • Uncontrolled invasion of 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.

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): NCT03035422


Contacts
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Contact: DULERY, PH 01.49.28.26.20 remy.dulery@aphp.fr
Contact: Mohamad MOHTY, PUPH 01.49.28.26.20 mohamad.mohty@inserm.fr

Locations
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France
Service d'hématologie Clinique Hôpital Saint Antoine Recruiting
Paris, France, 75012
Contact: Rémy DULERY, PH    01.49.28.26.20    remy.dulery@aphp.fr   
Contact: Mohamad MOHTY, PUPH    01.49.28.26.20    mohamad.mohty@inserm.fr   
Sponsors and Collaborators
Association for Training, Education, and Research in Hematology, Immunology, and Transplantation

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Responsible Party: Association for Training, Education, and Research in Hematology, Immunology, and Transplantation
ClinicalTrials.gov Identifier: NCT03035422     History of Changes
Other Study ID Numbers: 2016-A00862-49
First Posted: January 30, 2017    Key Record Dates
Last Update Posted: January 30, 2019
Last Verified: January 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Association for Training, Education, and Research in Hematology, Immunology, and Transplantation:
Allogenic cell stem transplant, Sequential chemotherapy Haploidentical transplant

Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists