Ignite Creation Date:
2024-05-06 @ 4:07 PM
Last Modification Date:
2024-10-26 @ 2:04 PM
Study NCT ID:
NCT04888741
Status:
RECRUITING
Last Update Posted:
2023-09-28
First Post:
2021-03-03
Brief Title:
Methods of T Cell Depletion Trial MoTD
Sponsor:
University of Birmingham
Organization:
University of Birmingham
Study Overview
Official Title:
A Multi-centre Phase II Trial of GVHD Prophylaxis Following Unrelated Donor Stem Cell Transplantation Comparing Thymoglobulin vs Calcineurin Inhibitor or Sirolimus-based Post-transplant Cyclophosphamide
Status:
RECRUITING
Status Verified Date:
2023-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
MoTD
Brief Summary:
A multi-centre phase II trial of GvHD prophylaxis following unrelated donor stem cell transplantation comparing Thymoglobulin vs Calcineurin inhibitor or Sirolimus-based post-transplant cyclophosphamide
Detailed Description:
This is a prospective phase II adaptive multicentre randomised clinical trial in patients undergoing reduced intensity conditioned RIC unrelated donor allogeneic stem cell transplantation allo-SCT The trial will compare the novel graft-versus-host disease GvHD prophylaxis regimens of post-transplant cyclophosphamide PTCy Calcineurin inhibitor CNI PTCy-CNI or PTCy Sirolimus to a current standard-of-care involving the use of T-cell depletion with Thymoglobulin Patients will be minimised at randomisation by their randomising centre disease risk score lowintermediate or highvery high and human leukocyte antigen HLA match 1010 or 910 Patients eligible for entry into the trial will be randomised on a 111 ratio to receive either one of the experimental treatment arms or the control arm
The primary objective is to compare GvHD-free relapse-free Survival GRFS in patients treated with the GvHD prophylaxis regimens PTCy-CNI PTCy-Sirolimus or T-cell depletion with Thymoglobulin
The secondary objectives are to evaluate the cumulative incidence of acute GvHD aGvHD the cumulative incidence of moderate and severe chronic GvHD cGvHD the cumulative incidence of non-relapse mortality NRM overall survival OS progression-free survival PFS immune suppression-free survival the cumulative incidence of engraftment the incidence of full donor chimerism the cumulative incidence of infection requiring inpatient admission the number of inpatient days the timing and dose of donor lymphocyte infusion DLI the cumulative incidence of Epstein-Barr virus EBV related-post transplant lymphoproliferative disease PTLD the number of doses rituximab administered for EBV reactivation quality of life QoL the cumulative incidence of haemorrhagic cystitis the cumulative incidence of cytomegalovirus CMV viraemia and CMV end-organ disease and safety and tolerability
The scientific research will address the questions about how plasma biomarkers for GvHD predict GvHD and non-relapse mortality following T-cell depleted methods of transplantation and how the different methods of T-cell depletion impact on immune function and re-constitution
Outcome Measures
Primary Outcome Measure
GvHD-free relapse-free survival at 1 year
Secondary Outcome Measures
Cumulative incidence of acute grade II-IV and III-IV GvHD at 1 year
Cumulative incidence of moderate and severe chronic GvHD at 1 year
Cumulative incidence of NRM at 1 year
Overall survival at 1 year
Progression-free survival at 1 year
Immune suppression-free survival at 1 year
Cumulative incidence of engraftment at 1 year
The incidence of full donor chimerism at 100 days
The cumulative incidence of infection requiring inpatient admission at 1 year
The number of inpatient days during first 12 months
The timing and dose of DLI for mixed chimerism persistent disease or relapse
Cumulative incidence of EBV-related PTLD
The number of doses of rituximab administered for EBV reactivation during first 12 months
QoL measured by FACT-BMT questionnaire at baseline 6 months and 12 months
Cumulative incidence of patients with haemorrhagic cystitis at 1 year
Cumulative incidence of CMV viremia and CMV end-organ disease at 1 year
Safety defined as the incidence of grade 3 toxicities reported as per the National Cancer Institute Common Terminology Criteria for Adverse Events NCI CTCAE v40
Tolerability defined to be the number of patients able to complete therapy as scheduled
Exploratory Outcome Measures
The scientific research will address the following questions
1 Do plasma biomarkers for GvHD predict GvHD and non-relapse mortality following T-cell depleted methods of transplantation
2 Do PTCy methods increase T cell receptor repertoire diversity as measured by TCR DNA sequencing compared to ATG-based T cell depletion
3 How do the different methods of T-cell depletion impact upon donor Treg reconstitution
4 How do the different methods of T-cell depletion impact upon thymic function as evaluated by measurement of recent thymic emigrants
5 Are PTCy methods of TCD associated with better preservation of virus-specific immunity as measured by tetramer or ex vivo functional immune responses
Patient Population
Adults considered suitable for an allo-SCT with the following haematological malignancies will be recruited to this trial
Acute Myeloid Leukaemia AML
Acute lymphoblastic leukaemia ALL
Chronic myelomonocytic leukemia CMML
Myelodysplastic syndromes MDS
Non-Hodgkin lymphoma NHL
Hodgkin lymphoma HL
Multiple myeloma MM
Chronic lymphocytic leukaemia CLL
Chronic myeloid leukaemia CML
Myelofibrosis
Sample Size
Up to 400 patients will be randomised to the MoTD trial across IMPACT centres
Trial Duration
Patients will be recruited over 48 months Patients will be followed up for a minimum of 1 year
MoTD Trials Office Contact Details
MoTD trials office Centre for Clinical Haematology Queen Elizabeth Hospital Edgbaston Birmingham B15 2TH Tel 0121 371 7858 Email MoTDtrialsbhamacuk
The primary objective is to compare GvHD-free relapse-free Survival GRFS in patients treated with the GvHD prophylaxis regimens PTCy-CNI PTCy-Sirolimus or T-cell depletion with Thymoglobulin
The secondary objectives are to evaluate the cumulative incidence of acute GvHD aGvHD the cumulative incidence of moderate and severe chronic GvHD cGvHD the cumulative incidence of non-relapse mortality NRM overall survival OS progression-free survival PFS immune suppression-free survival the cumulative incidence of engraftment the incidence of full donor chimerism the cumulative incidence of infection requiring inpatient admission the number of inpatient days the timing and dose of donor lymphocyte infusion DLI the cumulative incidence of Epstein-Barr virus EBV related-post transplant lymphoproliferative disease PTLD the number of doses rituximab administered for EBV reactivation quality of life QoL the cumulative incidence of haemorrhagic cystitis the cumulative incidence of cytomegalovirus CMV viraemia and CMV end-organ disease and safety and tolerability
The scientific research will address the questions about how plasma biomarkers for GvHD predict GvHD and non-relapse mortality following T-cell depleted methods of transplantation and how the different methods of T-cell depletion impact on immune function and re-constitution
Outcome Measures
Primary Outcome Measure
GvHD-free relapse-free survival at 1 year
Secondary Outcome Measures
Cumulative incidence of acute grade II-IV and III-IV GvHD at 1 year
Cumulative incidence of moderate and severe chronic GvHD at 1 year
Cumulative incidence of NRM at 1 year
Overall survival at 1 year
Progression-free survival at 1 year
Immune suppression-free survival at 1 year
Cumulative incidence of engraftment at 1 year
The incidence of full donor chimerism at 100 days
The cumulative incidence of infection requiring inpatient admission at 1 year
The number of inpatient days during first 12 months
The timing and dose of DLI for mixed chimerism persistent disease or relapse
Cumulative incidence of EBV-related PTLD
The number of doses of rituximab administered for EBV reactivation during first 12 months
QoL measured by FACT-BMT questionnaire at baseline 6 months and 12 months
Cumulative incidence of patients with haemorrhagic cystitis at 1 year
Cumulative incidence of CMV viremia and CMV end-organ disease at 1 year
Safety defined as the incidence of grade 3 toxicities reported as per the National Cancer Institute Common Terminology Criteria for Adverse Events NCI CTCAE v40
Tolerability defined to be the number of patients able to complete therapy as scheduled
Exploratory Outcome Measures
The scientific research will address the following questions
1 Do plasma biomarkers for GvHD predict GvHD and non-relapse mortality following T-cell depleted methods of transplantation
2 Do PTCy methods increase T cell receptor repertoire diversity as measured by TCR DNA sequencing compared to ATG-based T cell depletion
3 How do the different methods of T-cell depletion impact upon donor Treg reconstitution
4 How do the different methods of T-cell depletion impact upon thymic function as evaluated by measurement of recent thymic emigrants
5 Are PTCy methods of TCD associated with better preservation of virus-specific immunity as measured by tetramer or ex vivo functional immune responses
Patient Population
Adults considered suitable for an allo-SCT with the following haematological malignancies will be recruited to this trial
Acute Myeloid Leukaemia AML
Acute lymphoblastic leukaemia ALL
Chronic myelomonocytic leukemia CMML
Myelodysplastic syndromes MDS
Non-Hodgkin lymphoma NHL
Hodgkin lymphoma HL
Multiple myeloma MM
Chronic lymphocytic leukaemia CLL
Chronic myeloid leukaemia CML
Myelofibrosis
Sample Size
Up to 400 patients will be randomised to the MoTD trial across IMPACT centres
Trial Duration
Patients will be recruited over 48 months Patients will be followed up for a minimum of 1 year
MoTD Trials Office Contact Details
MoTD trials office Centre for Clinical Haematology Queen Elizabeth Hospital Edgbaston Birmingham B15 2TH Tel 0121 371 7858 Email MoTDtrialsbhamacuk
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
False
Is an FDA AA801 Violation?:
None