Haemato-lymphoid Malignancies or Syndromes in Whom Allogeneic Stem Cell Transplantation is WarrantedPhase 2TLI-ATGNCT01566656
Allogeneic Hematopoietic Stem Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-thymocyte Globulin for Older Patients With Relapsed Lymphoid Malignancies
A Phase 2 study testing total lymphoid irradiation and anti-thymocyte globulin in people with Haemato-lymphoid Malignancies or Syndromes in Whom Allogeneic Stem Cell Transplantation is Warranted, run by Nantes University Hospital at 4 sites in France.
Trial summary
Recent advances in allogeneic hematopoietic cell transplantation (allo-SCT) have led to reduce intensity preparative regimens that are non-myeloablative and reduce the toxicities associated with the transplant. Consequently non-relapse mortality has been reduced, including in elderly patients with comorbidities. Read more about this study
- Who is it for?
- Ages 50 to 66 years
- Conditions the study is for
- Haemato-lymphoid Malignancies or Syndromes in Whom Allogeneic Stem Cell Transplantation is Warranted
- What is being tested?
- total lymphoid irradiation and anti-thymocyte globulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 4 sitesFrance
- Study dates
- 2 Mar 2012to 29 Nov 2016
- Phase
- Phase 2
- 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 50 to 66 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Any patient with one of the following hemato-lymphoid malignancies or syndromes in whom allogeneic stem cell transplantation is warranted. Specific disease categories include: non-follicular indolent advanced stage Non-Hodgkin Lymphomas, Mantle Cell Lymphoma, Marginal zone lymphoma, MALT, T cell lymphoma, Chronic Lymphocytic or prolymphocytic Leukemia, Hodgkin Disease, and Waldenström macroglobulinemia. T-cell NOS, angioimmunoblastic lymphoma, HTLV1, T-gamma/delta, anaplastic lymphoma and Sezeay syndromes can be included after careful assessment by the PI and the protocol steering committee.
- Patients must be at least in partial remission (according to standard criteria) after salvage therapy and before (~one month) the start of the conditioning regimen.
- Patient age >50 and less than 66 years, or for patients <50 years of age but because of pre-existing medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional myeloablative transplants.
- A fully HLA-identical sibling or matched unrelated donor is available (10/10 HLA match). Patients with one antigen mismatched donors can be considered but only after discussion with the transplant team and the Principal Investigator.
- Patient must be competent to give consent.
Who cannot join
- Patients with progressive hematolymphoid malignancies despite conventional therapies, and not in partial remission during the month preceding transplantation.
- Patients with DLBCL or cutaneous T cell lymphoma
- Uncontrolled CNS involvement with disease
- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
- Females who are pregnant
- Organ dysfunction defined as follows:
Show all 16Show fewer
- Cardiac function: ejection fraction <30% or uncontrolled cardiac failure
- Pulmonary: DLCO <40% predicted
- Renal: Serum creatinine >1.0 mg/dL; if serum creatinine >1.0 mg/dL, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m²
- Liver function abnormalities: elevation of bilirubin to > 3 mg/dl and/or transaminases >4x the upper limit of normal
- Karnofsky performance score < 70%
- Patients with poorly controlled hypertension on multiple antihypertensives
- Documented fungal disease that is progressive despite treatment
- Viral infections: HIV positive patients. Hepatitis B and C positive patients will be evaluated on a case by case basis
- Psychiatric disorders or psychosocial problems which in the opinion of the primary physician or Principal Investigator would place the patient at unacceptable risk from this regimen.
- Patients with prior malignancies diagnosed > 5 years ago without evidence of disease are eligible. Patients with a prior malignancy treated < 5 years ago but have a life expectancy of > 5 years for that malignancy are eligible.
Trial locations and contacts
4 sites in 1 country.
France4 sites
Besançon University Hospital
Besançon
Lille University Hospital
Lille
Lyon University Hospital
Lyon
Nantes University Hospital
Nantes
About this study
Recent advances in allogeneic hematopoietic cell transplantation (allo-SCT) have led to reduce intensity preparative regimens that are non-myeloablative and reduce the toxicities associated with the transplant. Consequently non-relapse mortality has been reduced, including in elderly patients with comorbidities. However, despite this benefit in terms of toxicity, excessive reduction of the intensity preparative regimens may favor relapse of the initial illness. Thus, acute and chronic graft-versus-host disease and opportunistic fungal and viral infections are always serious complications. The aim of our study is to check if a new modality of reduced intensity preparative regimen combining total lymphoid irradiation (TLI) and thymoglobulin (ATG), would limit the toxicity of treatment and reduce the incidence of acute GVHD after allogeneic transplantation while preserving the antitumor benefit.
- Conditions
- Haemato-lymphoid Malignancies or Syndromes in Whom Allogeneic Stem Cell Transplantation is Warranted
- Being tested
- total lymphoid irradiation and anti-thymocyte globulin
- Keywords
- Allogeneic hematopoietic stem cell transplantation, Non-myeloablative preparative regimen, Total lymphoid irradiation, Anti-thymocyte globulin, Lymphoid malignancies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
total lymphoid irradiation and anti-thymocyte globulinDrug
- TLI Administration: TLI is administered ten times in 120 cGy fractions on day -11 through day -7 and day -4 through day -1.
- ATG: Thymoglobulin will be administered five times intravenously at 1.5 mg/kg/day from day -11 through day -7 for a total dose of 7.5 mg/kg.
- Mobilized PBSCs (Day 0): The desired cell doses (based on recipient body weight) for MRD and MUD transplants are around 4-8 x106 CD34+ cells/kg.
- GVHD Prophylaxis: Cyclosporine A (CSP) 3 mg/kg IV from day-3 and Mycophenylate mofetil (MMF) 500 mg x 4/ day PO from day 0
| Study group | Role | What they receive |
|---|---|---|
| TLI and anti-thymocyte globulin | Experimental | Not described Receives: Drug: total lymphoid irradiation and anti-thymocyte globulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the incidence of non-relapse mortality (NRM)
Measured: one year after transplantation
Secondary outcomes (3)
Neutrophil and platelets recovery and chimerism measurement
To evaluate the kinetics of donor hematopoietic cell engraftment (neutrophil and platelets recovery) and chimerism.
T cell subsets, regulatory cells, NK cells and B cells measurement
To document the quantitative and qualitative reconstitution of the immune system including T cell subsets, regulatory cells, NK cells and B cells.
Number of relapse, acute and chronic GVHD
To evaluate the rate of relapse, overall and event-free survival and incidence of acute and chronic GVHD, at one year after transplantation.
Measured: one year after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2012 (estimated)
- Study start2 Mar 2012
- Primary completion29 Nov 2016
- Study completion29 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Haemato-lymphoid Malignancies or Syndromes in Whom Allogeneic Stem Cell Transplantation is WarrantedStudies of the same condition, open and under way.
- More trials run by Nantes University HospitalThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nantes University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mohamad MOHTY, Pr, Principal investigator, Hôpital Saint Antoine (AP-HP)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01566656
- Sponsor's protocol ID
- BRD/10/06-L
- Acronym
- TLI-ATG
- Status last verified
- Apr 2018
- First submitted
- 27 Mar 2012
- Last updated
- 5 Apr 2018
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Allogeneic Hematopoietic Stem Cell Transplantation Using a Non-myeloablative Preparative Regimen of Total Lymphoid Irradiation and Anti-thymocyte Globulin for Older Patients With Relapsed Lymphoid Malignancies
- ClinicalTrials.gov ID
- NCT01566656
- Acronym / sponsor ID
- TLI-ATG / BRD/10/06-L
- Conditions
- Haemato-lymphoid Malignancies or Syndromes in Whom Allogeneic Stem Cell Transplantation is Warranted
- Keywords
- Allogeneic hematopoietic stem cell transplantation, Non-myeloablative preparative regimen, Total lymphoid irradiation, Anti-thymocyte globulin, Lymphoid malignancies
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Nantes University HospitalUniversity, hospital or other
- Study start
- 2 Mar 2012 (actual)
- Primary completion
- 29 Nov 2016 (actual)
- Study completion
- 29 Nov 2016 (actual)
- First posted
- 29 Mar 2012 (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.
Recent advances in allogeneic hematopoietic cell transplantation (allo-SCT) have led to reduce intensity preparative regimens that are non-myeloablative and reduce the toxicities associated with the transplant. Consequently non-relapse mortality has been reduced, including in elderly patients with comorbidities. However, despite this benefit in terms of toxicity, excessive reduction of the intensity preparative regimens may favor relapse of the initial illness. Thus, acute and chronic graft-versus-host disease and opportunistic fungal and viral infections are always serious complications. The aim of our study is to check if a new modality of reduced intensity preparative regimen combining total lymphoid irradiation (TLI) and thymoglobulin (ATG), would limit the toxicity of treatment and reduce the incidence of acute GVHD after allogeneic transplantation while preserving the antitumor benefit.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| TLI and anti-thymocyte globulin | Experimental | Drug: total lymphoid irradiation and anti-thymocyte globulin |
Who may qualify
- Ages
- 50 to 66 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Any patient with one of the following hemato-lymphoid malignancies or syndromes in whom allogeneic stem cell transplantation is warranted. Specific disease categories include: non-follicular indolent advanced stage Non-Hodgkin Lymphomas, Mantle Cell Lymphoma, Marginal zone lymphoma, MALT, T cell lymphoma, Chronic Lymphocytic or prolymphocytic Leukemia, Hodgkin Disease, and Waldenström macroglobulinemia. T-cell NOS, angioimmunoblastic lymphoma, HTLV1, T-gamma/delta, anaplastic lymphoma and Sezeay syndromes can be included after careful assessment by the PI and the protocol steering committee.
- Patients must be at least in partial remission (according to standard criteria) after salvage therapy and before (~one month) the start of the conditioning regimen.
- Patient age >50 and less than 66 years, or for patients <50 years of age but because of pre-existing medical conditions or prior therapy are considered to be at high risk for regimen-related toxicity associated with conventional myeloablative transplants.
- A fully HLA-identical sibling or matched unrelated donor is available (10/10 HLA match). Patients with one antigen mismatched donors can be considered but only after discussion with the transplant team and the Principal Investigator.
- Patient must be competent to give consent.
Key exclusion criteria (16 listed)
- Patients with progressive hematolymphoid malignancies despite conventional therapies, and not in partial remission during the month preceding transplantation.
- Patients with DLBCL or cutaneous T cell lymphoma
- Uncontrolled CNS involvement with disease
- Fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment
- Females who are pregnant
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 |
|---|---|---|
| total lymphoid irradiation and anti-thymocyte globulin* TLI Administration: TLI is administered ten times in 120 cGy fractions on day -11 through day -7 and day -4 through day -1. * ATG: Thymoglobulin will be administered five times intravenously at 1.5 mg/kg/day from day -11 through day -7 for a total dose of 7.5 mg/kg. * Mobilized PBSCs (Day 0): The desired cell doses (based on recipient body weight) for MRD and MUD transplants are around 4-8 x106 CD34+ cells/kg. * GVHD Prophylaxis: Cyclosporine A (CSP) 3 mg/kg IV from day-3 and Mycophenylate mofetil (MMF) 500 mg x 4/ day PO from day 0 | Drug | TLI and anti-thymocyte globulin |
Primary outcome
To evaluate the incidence of non-relapse mortality (NRM)
Time frame: one year after transplantation
3 secondary outcomes
Neutrophil and platelets recovery and chimerism measurement
T cell subsets, regulatory cells, NK cells and B cells measurement
Number of relapse, acute and chronic GVHD
Time frame: one year 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 5 Apr 2018.
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.
Mohamad MOHTY, Pr principal investigator
Hôpital Saint Antoine (AP-HP)
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing total lymphoid irradiation and anti-thymocyte globulin in people with Haemato-lymphoid Malignancies or Syndromes in Whom Allogeneic Stem Cell Transplantation is Warranted, run by Nantes University Hospital at 4 sites 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 5 inclusion and 16 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 5 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
To evaluate the incidence of non-relapse mortality (NRM) (time frame: one year 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 5 Apr 2018.