- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03035422
Sequential Conditioning in Haploidentical Transplantation for Refractory Acute Myeloid Leukemia (SET-HAPLO)
Sequential Chemotherapy Prior to Reduced Intensity Conditioning: Interventional Study in Haploidentical Hematopoietic Stem Cells Transplantation for Patients With Refractory Acute Myeloid Leukemia
Study Overview
Status
Conditions
Detailed Description
The goal is to evaluate the efficacy and safety of the combination of an SET followed by haploidentical transplant with post-transplant immune modulation by prophylactic DLI in patients with refractory acute myeloid leukemia or relapsed. The main objective is to assess overall survival at 2 years in these patients.
Secondary objectives:
- To evaluate the efficacy of this therapeutic strategy in terms of remission of disease, incidence of relapse and relapse-free survival
- To evaluate the non-relapse mortality
- To evaluate the incidence of acute and chronic graft against host disease (GVHD)
- To assess the feasibility of prophylactic injections of donor lymphocytes (pDLI)
- To analyze the post-transplant immune reconstitution
Secondary endpoints:
partial or complete remission rate by standard criteria at 90 days and then 6, 12 and 24 months after transplantation.
Relapse incidence and death related to the disease 90 days 6, 12 and 24 months after transplantation Leukemia-free survival at 1 year and 2 years after transplantation
- Cumulative incidence of death not related to relapse at 90 days, 1 year and 2 years after transplantation
- Cumulative incidence of acute and chronic graft against host disease (GVHD)
- Number of patients for whom pDLI was possible and number of pDLI / patient; incidence, severity and treatment of possible secondary GVHD in these patients
- Study of immune reconstitution post-transplant in the peripheral blood 30, 90 and 180 days after transplantation (CD4 lymphocyte levels, CD8, T regulators, Natural Killer cells and B cells)
Methodology, experimental design:
Multicenter study in routine care, prospective
All patients will receive, as part of the marketing authorization of the products used, the following regimen:
1- 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)
- Rest 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)
2 Graft transfusion: the day D0. A graft of peripheral stem cells is preferred.
3- 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)
4- Care supports: according to the protocols of each center
5- lymphocyte injection of prophylactic donor (pDLI): according to the protocols of each center. The following scheme is proposed:
- In the absence of clinical contraindication(GVHD), tapering MMF between days D + 35 and D + 56, then tapering CSA between D + 62 and D + 90
pDLI: 3 injections from the D + 120 in patients who discontinued immunosuppressive therapy for ≥ 1 month and having no active GVHD or history of acute GVHD grade> II.
6. Feedback: at baseline and 1, 3, 6, 12 and 24 months after transplant (engraftment, disease response, immune reconstitution, chimerism, GVHD, infection, quality of life).
The treatments evaluated in this strategy are all used in the usual care of patients and follow-up will not be changed.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Paris, France, 75012
- Service d'hématologie Clinique Hôpital Saint Antoine
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: OTHER
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
OTHER: Patients with primary refractory acute myeloid leukemia
|
According to the protocols of each center
Sequential chemotherapy:
Graft of peripheral stem cells is preferred at D0
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 |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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. |
2 years after transplantation
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
90 days and then 6, 12 and 24 months after transplantation
|
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
|
90 days and then 12 and 24 months after transplantation
|
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)
|
100 days and then 12 and 24 months after transplantation
|
Number of patients for whom pDLI was possible.
Time Frame: 2 years after transplantation
|
Assess the feasibility of prophylactic injections of donor lymphocytes (pDLI)
|
2 years after transplantation
|
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
|
90 days and then 6, 12 and 24 months after transplantation
|
Leukemia free survival
Time Frame: 90 days and then 6, 12 and 24 months after transplantation
|
Relapse-free survival
|
90 days and then 6, 12 and 24 months after transplantation
|
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)
|
90 days and then 6, 12 and 24 months after transplantation
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2016-A00862-49
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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