Refractory or Relapsed Lymphoid HaemopathyLY-SET-HAPLONCT03079089
Sequential Conditioning in Haploidentical Transplantation for Hematopoietic Stem Cells in Patients With Relapsed or Refractory Lymphoid Hematological Disorders
A study testing Sequential Packaging (SET), Transfusion graft and Prevention of GVHD in people with Refractory or Relapsed Lymphoid Haemopathy, 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 lymphoid hematological refractory or multiple relapses after chemotherapy. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Refractory or Relapsed Lymphoid Haemopathy
- 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
- 40 participants
- Where
- 1 siteFrance
- Study dates
- 30 Jun 2017to 11 Sep 2023
- 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 an indication of allo-HSC for a lymphoid hematological malignancy like Hodgkin's lymphoma, non hodgkin's lymphoma b cell (mantle follicular, diffuse large cells, marginal zone,MALT) or T (peripheral T whithout specificity, anaplasic, angio-immunoblastic, natural killer cells, gamma / delta T cells, Sezary's syndrome, primitive cutaneous T), prolymphocytic leukemia, chronic lymphocytic leukemia, waldenström's disease and for which a therapeutic strategie combining a sequential chemotherapy followed by the reduced-intensity conditioning(SET RIC + PDLI) is decided
- Patients at least in partial response (standard criteria) after a rescue treatment the day of evaluation at 1 month before the conditioning
- Advanced 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
- Invasion of uncontrolled 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 11Show 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.
- life expentancy estimated less than 1 month by investigator
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Sequential Chemotherapy Prior Conditioning Reduced Intensity: Study Routine Care in Haploidentical Allogeneic Hematopoietic Stem Cells in Patients With Relapsed or Refractory Lymphoid Hematological Disorders
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is the only treatment option with a significant chance of healing in lymphoid hematological refractory or 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.
For patients refractory or in relapses with an indication of allo-HSC, used the combinaison of an SET followed by the reduced-intensity allo-HSC (RIC) has shown some interesting results.
A post-transplant immune modulation with prophylactic injections of donor lymphocytes (PDLI) showed its effectiveness to decrease the risk of relapse while having a lower toxicity than chemotherapy
- 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
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 DO
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 |
|---|---|---|
| Relapsed or refractory lymphoid hematological disorders | Other | Patients in refractory or relapses with an indication of allo-HSC used the combination of an SET followed by the RIC with the PDLI 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)
Describe efficacy and safety of the combination of an SET followed by the RIC with post-transplant immune modulation by PDLI in patients with refractory or relaps lymphoid hematological refractory or multiple relapses lymphoid hematological disorders
Measured: 2 years after transplantation
Secondary outcomes (6)
Partial or complete remission rate by standard criteria relapse incidence and death related to the disease and free survival
Describe the efficacy of this therapeutic strategy in terms of remission of disease, incidence of relapse and relapse-free survival
Measured: 90 days and then 6, 12 and 24 months after transplantation
Cumulative incidence of death not related to relapse
Describe 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)
Describe 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 and number PDLI / patient ; incidence, severity and treatment of possible secondary GVHD in these patients
Describe the feasibility of prophylactic injections of donor lymphocytes (PDLI)
Measured: 2 years after transplantation
Immune reconstitution post-transplantation in the peripheral blood
Immune reconstitution will be determined by CD4 lymphocyte, CD8, T regulators, Natural Killer cells and B cells levels in the peripheral blood
Measured: 30, 90 and 180 days after transplantation
Tolerance of this therapeutic strategy
The tolerance will be evaluated by:
- The cumulative incidence of death not related to relapse at 90 days, 1 year and 2 years after transplantation
- The cumulative incidence of acute and chronic graft against host disease (GVHD)
- The incidence of advert events
Measured: 90 days and the 6, 12 and 24 month after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2017
- Study start30 Jun 2017
- Primary completion11 Sep 2023
- Study completion11 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Refractory or Relapsed Lymphoid HaemopathyStudies 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
- Model description
- Patients with refractory or relaps lymphoid hematological disorders
- Masking
- None (open label)
- Enrolment
- 40 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
- Principal investigator, Pr Mohamad MOHTY, Association for Training, Education, and Research in Hematology, Immunology, and Transplantation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03079089
- Sponsor's protocol ID
- 2016-A00861-50
- Acronym
- LY-SET-HAPLO
- Status last verified
- Jul 2024
- First submitted
- 16 Feb 2017
- Last updated
- 30 Jul 2024
- 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 30 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Sequential Chemotherapy Prior Conditioning Reduced Intensity: Study Routine Care in Haploidentical Allogeneic Hematopoietic Stem Cells in Patients With Relapsed or Refractory Lymphoid Hematological Disorders
- ClinicalTrials.gov ID
- NCT03079089
- Acronym / sponsor ID
- LY-SET-HAPLO / 2016-A00861-50
- Keywords
- Allogenic cell stem transplant, Sequential chemotherapy, Haploidentical transplant
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Association for Training, Education, and Research in Hematology, Immunology, and TransplantationUniversity, hospital or other
- Study start
- 30 Jun 2017 (actual)
- Primary completion
- 11 Sep 2023 (actual)
- Study completion
- 11 Sep 2023 (actual)
- First posted
- 14 Mar 2017 (actual)
- 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 lymphoid hematological refractory or 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.
For patients refractory or in relapses with an indication of allo-HSC, used the combinaison of an SET followed by the reduced-intensity allo-HSC (RIC) has shown some interesting results.
A post-transplant immune modulation with prophylactic injections of donor lymphocytes (PDLI) showed its effectiveness to decrease the risk of relapse while having a lower toxicity than chemotherapy
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Patients with refractory or relaps lymphoid hematological disorders
| Arm | Type | Receives |
|---|---|---|
| Relapsed or refractory lymphoid hematological disorders | Other | Drug: Sequential Packaging (SET), Drug: Transfusion graft, Drug: Prevention of GVHD, Drug: Care supports, Drug: Lymphocyte injection of prophylactic donor (PDLI)Patients in refractory or relapses with an indication of allo-HSC used the combination of an SET followed by the RIC with the PDLI |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Patients with an indication of allo-HSC for a lymphoid hematological malignancy like Hodgkin's lymphoma, non hodgkin's lymphoma b cell (mantle follicular, diffuse large cells, marginal zone,MALT) or T (peripheral T whithout specificity, anaplasic, angio-immunoblastic, natural killer cells, gamma / delta T cells, Sezary's syndrome, primitive cutaneous T), prolymphocytic leukemia, chronic lymphocytic leukemia, waldenström's disease and for which a therapeutic strategie combining a sequential chemotherapy followed by the reduced-intensity conditioning(SET RIC + PDLI) is decided
- Patients at least in partial response (standard criteria) after a rescue treatment the day of evaluation at 1 month before the conditioning
- Advanced 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
Key exclusion criteria (11 listed)
- Invasion of uncontrolled 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 | Relapsed or refractory lymphoid hematological disorders |
| Transfusion graftGraft of peripheral stem cells is preferred at DO | Drug | Relapsed or refractory lymphoid hematological disorders |
| 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 | Relapsed or refractory lymphoid hematological disorders |
| Care supportsAccording to the protocols of each center | Drug | Relapsed or refractory lymphoid hematological disorders |
| 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 | Relapsed or refractory lymphoid hematological disorders |
Primary outcome
Overall survival (OS)
Time frame: 2 years after transplantation
Describe efficacy and safety of the combination of an SET followed by the RIC with post-transplant immune modulation by PDLI in patients with refractory or relaps lymphoid hematological refractory or multiple relapses lymphoid hematological disorders
6 secondary outcomes
Partial or complete remission rate by standard criteria relapse incidence and death related to the disease and free survival
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 and number PDLI / patient ; incidence, severity and treatment of possible secondary GVHD in these patients
Time frame: 2 years after transplantation
Immune reconstitution post-transplantation in the peripheral blood
Time frame: 30, 90 and 180 days after transplantation
Tolerance of this therapeutic strategy
Time frame: 90 days and the 6, 12 and 24 month 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 30 Jul 2024.
- Individual participant dataSharing planned: No
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 or Relapsed Lymphoid Haemopathy, 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 8 inclusion and 11 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 30 Jul 2024. 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 30 Jul 2024.