Refractory Acute Myeloid LeukemiaSET-HAPLONCT03035422
Sequential Conditioning in Haploidentical Transplantation for Refractory Acute Myeloid Leukemia
A study testing Sequential Packaging (SET), Transfusion graft and Prevention of GVHD in people with Refractory Acute Myeloid Leukemia, run by Association for Training, Education, and Research in Hematology, Immunology, and Transplantation at 1 site in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Refractory Acute Myeloid Leukemia
- What is being tested?
- Sequential Packaging (SET), Transfusion graft and Prevention of GVHD
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteFrance
- Study dates
- 15 Jan 2018to 18 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Sequential Chemotherapy Prior to Reduced Intensity Conditioning: Interventional Study in Haploidentical Hematopoietic Stem Cells Transplantation for Patients With Refractory Acute Myeloid Leukemia
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.
Read the 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.
- 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.
- Conditions
- Refractory Acute Myeloid Leukemia
- Being tested
- Sequential Packaging (SET), Transfusion graft, Prevention of GVHD, Care supports, Lymphocyte injection of prophylactic donor (PDLI)
- Keywords
- Allogenic cell stem transplant, Sequential chemotherapy Haploidentical transplant
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sequential Packaging (SET)Drug
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)
Transfusion graftDrug
Graft of peripheral stem cells is preferred at D0
Prevention of GVHDDrug
- 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)
Care supportsDrug
According to the protocols of each center
Lymphocyte injection of prophylactic donor (PDLI)Drug
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
| Study group | Role | What they receive |
|---|---|---|
| Patients with primary refractory acute myeloid leukemia | Other | Patients with primary refractory acute myeloid leukemia Receives: Drug: Sequential Packaging (SET); Drug: Transfusion graft; Drug: Prevention of GVHD; Drug: Care supports; Drug: Lymphocyte injection of prophylactic donor (PDLI) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS)
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.
Measured: 2 years after transplantation
Secondary outcomes (7)
Partial or complete remission rate by standard criteria Relapse incidence and death related to the disease
To evaluate the efficacy of this therapeutic strategy in terms of remission of disease, incidence of relapse
Measured: 90 days and then 6, 12 and 24 months after transplantation
Cumulative incidence of death not related to relapse
Assess not related to relapse mortality
Measured: 90 days and then 12 and 24 months after transplantation
Cumulative incidence of acute and chronic graft against host disease (GVHD)
To evaluate the incidence of acute and chronic graft against host disease (GVHD)
Measured: 100 days and then 12 and 24 months after transplantation
Number of patients for whom pDLI was possible.
Assess the feasibility of prophylactic injections of donor lymphocytes (pDLI)
Measured: 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
Study the post-transplant immune reconstitution
Measured: 90 days and then 6, 12 and 24 months after transplantation
Leukemia free survival
Relapse-free survival
Measured: 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
Assess the feasibility of prophylactic injections of donor lymphocytes (pDLI)
Measured: 90 days and then 6, 12 and 24 months after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2017 (estimated)
- Study start15 Jan 2018
- Primary completion18 Dec 2021
- Study completion18 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory Acute Myeloid LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Association for Training, Education, and Research in Hematology, Immunology, and Transplantation
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03035422
- Sponsor's protocol ID
- 2016-A00862-49
- Acronym
- SET-HAPLO
- Status last verified
- Jul 2022
- First submitted
- 24 Nov 2016
- Last updated
- 25 Jul 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sequential Chemotherapy Prior to Reduced Intensity Conditioning: Interventional Study in Haploidentical Hematopoietic Stem Cells Transplantation for Patients With Refractory Acute Myeloid Leukemia
- ClinicalTrials.gov ID
- NCT03035422
- Acronym / sponsor ID
- SET-HAPLO / 2016-A00862-49
- Conditions
- Refractory Acute Myeloid Leukemia
- Keywords
- Allogenic cell stem transplant, Sequential chemotherapy Haploidentical transplant
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Association for Training, Education, and Research in Hematology, Immunology, and TransplantationUniversity, hospital or other
- Study start
- 15 Jan 2018 (actual)
- Primary completion
- 18 Dec 2021 (actual)
- Study completion
- 18 Dec 2021 (actual)
- First posted
- 30 Jan 2017 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
- 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 design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients with primary refractory acute myeloid leukemia | Other | Drug: Sequential Packaging (SET), Drug: Transfusion graft, Drug: Prevention of GVHD, Drug: Care supports, Drug: Lymphocyte injection of prophylactic donor (PDLI)Patients with primary refractory acute myeloid leukemia |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 | Patients with primary refractory acute myeloid leukemia |
| Transfusion graftGraft of peripheral stem cells is preferred at D0 | Drug | Patients with primary refractory acute myeloid leukemia |
| 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 | Patients with primary refractory acute myeloid leukemia |
| Care supportsAccording to the protocols of each center | Drug | Patients with primary refractory acute myeloid leukemia |
| 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 | Drug | Patients with primary refractory acute myeloid leukemia |
Primary outcome
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.
7 secondary outcomes
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
Cumulative incidence of death not related to relapse
Time frame: 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
Number of patients for whom pDLI was possible.
Time frame: 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
Leukemia free survival
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2022.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Sequential Packaging (SET), Transfusion graft and Prevention of GVHD in people with Refractory Acute Myeloid Leukemia, run by Association for Training, Education, and Research in Hematology, Immunology, and Transplantation at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall survival (OS) (time frame: 2 years after transplantation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2022.