Acute Myeloid LeukemiaPhase 2MoTDNCT04888741
Methods of T Cell Depletion Trial (MoTD)
A Phase 2 study testing Thymoglobulin, Cyclophosphamide and Cyclosporine in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by University of Birmingham at 17 sites in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 16 to 70 years
- Conditions the study is for
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelomonocytic Leukemia
- What is being tested?
- Thymoglobulin, Cyclophosphamide and Cyclosporine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 400 participants
- Where
- 17 sitesUnited Kingdom
- Study dates
- 22 Feb 2021to 23 Aug 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 16 to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Availability of suitably matched unrelated donor (9/10 or 10/10)
- Planned to receive one of the following RIC protocols:
- Fludarabine-Melphalan (Fludarabine 120-180mg/m2 IV; melphalan ≤ 150mg/m2 IV)
- BEAM or LEAM (carmustine 300mg/m2 IV or lomustine 200mg/m2 IV with: etoposide 800 mg/m2 IV; cytarabine 1600mg/m2 IV; melphalan 140mg/m2 IV)
- Fludarabine-Busulphan (Fludarabine 120-180mg/m2 IV; Busulphan ≤ 8mg/kg PO or 6.4mg/kg IV)
- Fludarabine- Treosulfan (Fludarabine 150mg/m2 IV; Treosulfan 30g/m2 IV)
Show all 20Show fewer
- Planned use of PBSCs for transplantation
- Planned allo-SCT for one of the following haematological malignancies:
- AML in CR (patients enrolled onto the COSI trial are not eligible for this study)
- ALL in CR (patients enrolled onto the ALL-RIC trial are not eligible for this study)
- CMML <10% blasts
- MDS <10% blasts (patients enrolled onto the COSI trial are not eligible for this study)
- NHL in CR/PR
- HL in CR/PR
- MM in CR/PR
- CLL in CR/PR
- CML in 1st or 2nd chronic phase
- Myelofibrosis
- Age 16-70 years
- Females of and male patients of reproductive potential (i.e., not post-menopausal or surgically sterilised) must agree to use appropriate, highly effective, contraception from the point of commencing therapy until 12 months after transplant
Who cannot join
- Use of any method of graft manipulation (excluding storage of future DLI)
- Use of alemtuzumab or any method of T cell depletion except those that are protocol-defined
- Known hypersensitivity to study drugs or history of hypersensitivity to rabbits
- Pregnant or lactating women
- Adults of reproductive potential not willing to use appropriate, highly effective, contraception during the specified period
- Life expectancy <8 weeks
Show all 15Show fewer
- Active HBV or HCV infection
- Organ dysfunction defined as:
- LVEF <45%
- GFR <50ml/min
- Bilirubin >50µmol/l
- AST/ALT>3 x ULN
- Participation in COSI or ALL-RIC trials
- Contraindication to treatment with the study drugs (Thymoglobulin, cyclophosphamide, sirolimus, ciclosporin and mycophenolate mofetil) as detailed in each study drug SPC.
- Patient has any other systemic dysfunction (e.g., gastrointestinal, renal, respiratory, cardiovascular) or significant disorder which, in the opinion of the investigator would jeopardise the safety of the patient by taking part in the trial.
Trial locations and contacts
17 sites in 1 country. Contact the study team or a site near you to ask about taking part.
17 sites in 1 country
United Kingdom17 sites, 17 recruiting
- Recruiting
Queen Elizabeth Hospital
Birmingham, B15 2GW
- Recruiting
Bristol Haematology and Oncology Centre
Bristol, BS2 8ED
- Recruiting
Addenbrookes Hospital
Cambridge, CB2 0QQ
- Recruiting
University Hospital of Wales
Cardiff, Wales, CF14 4XW
Emma Kempshall
- Recruiting
Queen Elizabeth Hospital Glasgow
Glasgow, G51 4TF
Andrew Clark
- Recruiting
St Jame's University Hospital
Leeds, LS9 7TF
- Recruiting
University College London Hospital
London, NW1 2BU
- Recruiting
King's College Hospital
London, SE5 9RS
Pramilla Krishnamurphy
- Recruiting
Hammersmith Hospital
London, W12 0HS
- Recruiting
Manchester Royal Infirmary
Manchester, M13 9WL
- Recruiting
The Christie
Manchester, M20 3QH
- Recruiting
Freeman Hospital
Newcastle upon Tyne, NE7 7DN
- Recruiting
Nottingham City Hospital
Nottingham, NG5 1PB
- Recruiting
Churchill Hospital
Oxford, OX3 7LE
- Recruiting
Derriford Hospital
Plymouth, PL6 8DH
- Recruiting
Royal Hallamshire Hospital
Sheffield, S102JF
- Recruiting
The Royal Marsden Hospital
Sutton, SM2 5PT
About this study
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
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.
Read the 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 (low/intermediate or high/very high) and human leukocyte antigen (HLA) match (10/10 or 9/10). Patients eligible for entry into the trial will be randomised on a 1:1:1 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) v4.0
- 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:
- Do plasma biomarkers for GvHD predict GvHD and non-relapse mortality following T-cell depleted methods of transplantation?
- Do PTCy methods increase T cell receptor repertoire diversity (as measured by TCR DNA sequencing) compared to ATG-based T cell depletion?
- How do the different methods of T-cell depletion impact upon donor Treg reconstitution?
- How do the different methods of T-cell depletion impact upon thymic function as evaluated by measurement of recent thymic emigrants?
- 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: MoTD@trials.bham.ac.uk
- Conditions
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndromes, Non Hodgkin Lymphoma, Hodgkin Lymphoma
- Being tested
- Thymoglobulin, Cyclophosphamide, Cyclosporine, Sirolimus, Mycophenolate Mofetil
- Keywords
- GvHD, Allogeneic Stem Cell Transplant, AML, MDS, CML, CMML, NHL, HL, Cyclophosphamide, Thymoglobulin, Cyclosporin, Sirolimus, Mycophenolate Mofetil
- Medical subject headings
- Leukemia, Myeloid, Acute, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Myelomonocytic, Chronic, Myelodysplastic Syndromes, Lymphoma, Non-Hodgkin, Hodgkin Disease, Multiple Myeloma, Leukemia, Myelogenous, Chronic, BCR-ABL Positive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThymoglobulinDrug
Also called ATG
GVHD prophylaxis
CyclophosphamideDrug
Post transplant cyclophosphamide strategy for GVHD prophylaxis
CyclosporineDrug
immunosuppressant
SirolimusDrug
immunosuppressant
Also called MMF
immunosuppressant
| Study group | Role | What they receive |
|---|---|---|
| Control Arm Thymoglobulin + Cyclosporine + MMF | Active comparator | Thymoglobulin is given as an intravenous infusion of 2.5 mg/kg/day over 2 days (days -2 and -1; total dose 5 mg/kg) via a central line through a 0.2 micron inline filter. Each dose will be infused over 6-8 hours. No test dose will be given. 30 minutes before Thymoglobulin, the patient should receive methylprednisolone 1mg/kg intravenously, 1g paracetamol PO and 10mg chlorphenamine IV. Patients should be monitored carefully and receive appropriate therapy for any infusion-related or anaphylactic reactions as per local policy.
Patients will receive IV/PO cyclosporine according to local policy to begin on day -1 maintaining a trough level of 100-200 µg/L until day 90 before a subsequent taper in the absence of any active GvHD.
MMF will be given IV/PO according to local policy at a dose of 1g TDS to begin on day -1 and discontinued on day 35 without taper if there is no evidence of active GvHD. In adults weighing <55kg, MMF should be given at a lower dose of 0.75g IV/PO TDS. Receives: Drug: Thymoglobulin; Drug: Cyclosporine; Drug: Mycophenolate Mofetil |
| Experimental arm (PTCy + Cyclosporine + MMF) | Experimental | Cyclophosphamide is given as an IV infusion of 50 mg/kg/day over 2 days (days 3 and 4; total dose 100 mg/kg) together with IV hydration and Mesna, as per local policy.
Patients will receive IV/PO cyclosporine according to local policy to begin on day 5 maintaining a trough level of 100-200 µg/L until day 90 before a subsequent taper in the absence of active GvHD.
MMF will be given IV/PO according to local policy at a dose of 1g TDS to begin on day 5 and discontinued on day 35 without taper if there is no evidence of active GvHD. In adults weighing <55kg, MMF should be given at a lower dose of 0.75g IV/PO TDS. Receives: Drug: Cyclophosphamide; Drug: Cyclosporine; Drug: Mycophenolate Mofetil |
| Experimental arm (PTCy + Sirolimus + MMF) | Experimental | Cyclophosphamide is given as an IV infusion of 50 mg/kg/day over 2 days (days 3 and 4; total dose 100 mg/kg) together with IV hydration and Mesna, as per local policy.
Sirolimus will be initially given PO as a loading dose of 6 mg on day 5 followed by 2 mg daily; doses will be adjusted to maintain a trough level (in whole blood) of 8 to 14 ng/mL until day 60, thereafter 5-8 ng/mL until day 90. In the absence of active GvHD, the dose of sirolimus will be tapered from day 90. We recommend that the daily maintenance dose of sirolimus is reduced empirically to 0.5-1mg daily with concomitant treatment with a triazole anti-fungal agent.
MMF will be given IV/O according to local policy at a dose of 1g TDS to begin on day 5 and discontinued on day 35 without taper if there is no evidence of active GvHD. In adults weighing <55kg, MMF should be given at a lower dose of 0.75g IV/PO TDS. Receives: Drug: Cyclophosphamide; Drug: Sirolimus; Drug: Mycophenolate Mofetil |
What is being measured
The primary outcome is the main question the study is designed to answer.
GVHD-free, relapse-free survival
GVHD assessment scoring will be performed as per the modified Glucksberg criteria (revised by MAGIC) and the National Institutes of Health (NIH) criteria. GvHD-free, relapse-free survival (GRFS) defined as the time from date of day 0 (defined as the day of stem cell infusion) to the date of first event or death from any cause. An event is defined as GvHD (both acute and chronic), relapse or progression. Patients who are alive and event free at the end of the trial will be censored at their date of last follow-up
Measured: at 1 year
Secondary outcomes (19)
Cumulative incidence of acute grade II-IV and III-IV GvHD
GVHD assessment scoring will be performed as per the modified Glucksberg criteria (revised by MAGIC) and the National Institutes of Health (NIH) criteria. GvHD-free
Measured: at 1 year
Cumulative incidence of moderate and severe chronic GvHD
GVHD assessment scoring will be performed as per the modified Glucksberg criteria (revised by MAGIC) and the National Institutes of Health (NIH) criteria. GvHD-free
Measured: at 1 year
Cumulative incidence of NRM
Non-relapse mortality (NRM) is defined as the time from day 0 to date of non-relapse death. Patients who die post-relapse from any other cause will be considered a competing risk and patients alive at the end of the trial will be censored at their date last seen.
Measured: at 1 year
Overall survival
Overall survival (OS) is defined as the time from day 0 to date of death, from any cause. Patients who are alive at the end of the trial will be censored at their date last seen.
Measured: at 1 year
Progression-free survival
Progression-free survival (PFS) is defined as the time from day 0 to date of first relapse/progression or death from any cause. Patients who are alive and progression free at the end of the trial will be censored at their date last seen.
Measured: at 1 year
Immune suppression-free survival
Immune suppression-free survival is defined as time from day 0 to the date of first immunosuppressive agent use. Patients who are alive and immune suppression free at the end of the trial will be censored at their date last seen
Measured: at 1 year
Cumulative incidence of engraftment
Cumulative incidence of engraftment defined as time from day 0 to date of engraftment (Neutrophil engraftment defined to be the first of 3 consecutive days a neutrophil count ≥ 0.5×〖10〗^9/L is reached and platelet engraftment defined to be the first of 3 consecutive days an unsupported platelet count ≥ 20×〖10〗^9/L is reached). Patients who relapse/progress or die prior to relapse, progression or engraftment will be considered a competing risk at their date of relapse/progression for the former and date of death for the latter. Patients alive and engraftment free at the end of the trial will be censored at their date last seen.
Measured: at 1 year
The incidence of full donor chimerism
Engraftment will be assessed by lineage specific chimerism measurements. Lineage specific chimerism in both whole blood and T-cell compartments (where possible) will be assessed as per local procedure, performed at 3 monthly intervals for the first 12 months post-transplant; at day 100 and then months 6, 9 and 12. Tests should be performed in local laboratories.
Measured: at 100 days
The cumulative incidence of infection requiring inpatient admission
The cumulative incidence of infection requiring inpatient admission measured by blood test and tissue culture at 1 year
Measured: at 1 year
The number of inpatient days
The sum of inpatients days
Measured: during first 12 months
The timing of mixed chimerism, persistent disease or relapse
We will be recording the time (days, post-transplant) whenever mixed chimerism, persistent disease or relapse occurred post transplant
Measured: during first 12 months
Cumulative incidence of EBV-related PTLD
Measured by blood sample, EBV PCR testing.
Measured: during first 12 months
The number of doses of Rituximab administered for EBV reactivation
We will collect the number of doses every time the patient will receive Rituximab whenever there is EBV reactivation
Measured: during first 12 months
QoL measured by FACT-BMT questionnaire
QoL measured by FACT-BMT questionnaire at baseline, 6 months and 12 months. FACT-BMT Questionnaire uses Units on a scale 0-4, higher scores mean a better outcome.
Measured: at baseline, 6 months and 12 months
Cumulative incidence of patients with haemorrhagic cystitis
Cumulative incidence of patients with haemorrhagic cystitis measured by blood and urine sample at 1 year
Measured: at 1 year
Cumulative incidence of CMV viremia and CMV end-organ disease
Cumulative incidence of CMV viremia and CMV end-organ disease measured by blood sample at 1 year
Measured: 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) V4.0
. Safety defined as the incidence of ≥ grade 3 toxicities reported as per the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0. Details of all AEs will be documented and reported from the date of commencement of protocol defined treatment until 28 days after the administration of the last dose of IMP. Serious AEs will be reported from the date of consent.
Measured: from the date of commencement of protocol defined treatment until 28 days after the administration of the last dose of IMP.
Tolerability defined to be the number of patients able to complete therapy as scheduled
Tolerability defined to be the number of patients able to complete therapy as scheduled (excluding any patients who discontinued treatment due to toxicities
Measured: during first 12 months
Dose of Donor lymphocyte infusion (DLI) for mixed chimerism, persistent disease or relapse
We will be collecting the dose of DLI (CD3 Cells/kg) whenever required for mixed chimerism, persistent disease or relapse
Measured: during first 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 May 2021
- Study start22 Feb 2021
- Primary completion23 Aug 2027 (estimated)
- Study completion23 Aug 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for 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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Patients eligible for entry into the trial will be randomised on a 1:1:1 ratio to receive either one of the experimental treatment arms or the control arm.
- Masking
- None (open label)
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- The Jon Moulton Charity Trust, IMPACT (funded by NHS Blood & Transplant, Anthony Nolan and Leukaemia UK)
- Responsible party
- Sponsor
- Investigators
- Ronjon Professor Chakraverty, Study director, Oxford Cancer & Haematology Centre, The Churchill Hospital, Old Road - Headington, Oxford, OX3 7LE Email: ronjon.chakraverty@ndcls.ox.ac.uk
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04888741
- Sponsor's protocol ID
- RG_19-116
- Acronym
- MoTD
- Status last verified
- Apr 2026
- First submitted
- 3 Mar 2021
- Last updated
- 5 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- 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 5 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04888741
- Acronym / sponsor ID
- MoTD / RG_19-116
- Conditions
- Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelomonocytic Leukemia, Myelodysplastic Syndromes, Non Hodgkin Lymphoma, Hodgkin Lymphoma
- Keywords
- GvHD, Allogeneic Stem Cell Transplant, AML, MDS, CML, CMML, NHL, HL
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- University of BirminghamUniversity, hospital or other
- Collaborators
- The Jon Moulton Charity Trust, IMPACT (funded by NHS Blood & Transplant, Anthony Nolan and Leukaemia UK)
- Study start
- 22 Feb 2021 (actual)
- Primary completion
- 23 Aug 2027 (estimated)
- Study completion
- 23 Aug 2027 (estimated)
- First posted
- 17 May 2021 (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.
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 (low/intermediate or high/very high) and human leukocyte antigen (HLA) match (10/10 or 9/10). Patients eligible for entry into the trial will be randomised on a 1:1:1 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) v4.0
- 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:
- Do plasma biomarkers for GvHD predict GvHD and non-relapse mortality following T-cell depleted methods of transplantation?
- Do PTCy methods increase T cell receptor repertoire diversity (as measured by TCR DNA sequencing) compared to ATG-based T cell depletion?
- How do the different methods of T-cell depletion impact upon donor Treg reconstitution?
- How do the different methods of T-cell depletion impact upon thymic function as evaluated by measurement of recent thymic emigrants?
- 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: MoTD@trials.bham.ac.uk
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Patients eligible for entry into the trial will be randomised on a 1:1:1 ratio to receive either one of the experimental treatment arms or the control arm.
| Arm | Type | Receives |
|---|---|---|
| Control Arm Thymoglobulin + Cyclosporine + MMF | Active comparator | Drug: Thymoglobulin, Drug: Cyclosporine, Drug: Mycophenolate MofetilThymoglobulin is given as an intravenous infusion of 2.5 mg/kg/day over 2 days (days -2 and -1; total dose 5 mg/kg) via a central line through a 0.2 micron inline filter. Each dose will be infused over 6-8 hours. No test dose will be given. 30 minutes before Thymoglobulin, the patient should receive methylprednisolone 1mg/kg intravenously, 1g paracetamol PO and 10mg chlorphenamine IV. Patients should be monitored carefully and receive appropriate therapy for any infusion-related or anaphylactic reactions as per local policy. Patients will receive IV/PO cyclosporine according to local policy to begin on day -1 maintaining a trough level of 100-200 µg/L until day 90 before a subsequent taper in the absence of any active GvHD. MMF will be given IV/PO according to local policy at a dose of 1g TDS to begin on day -1 and discontinued on day 35 without taper if there is no evidence of active GvHD. In adults weighing <55kg, MMF should be given at a lower dose of 0.75g IV/PO TDS. |
| Experimental arm (PTCy + Cyclosporine + MMF) | Experimental | Drug: Cyclophosphamide, Drug: Cyclosporine, Drug: Mycophenolate MofetilCyclophosphamide is given as an IV infusion of 50 mg/kg/day over 2 days (days 3 and 4; total dose 100 mg/kg) together with IV hydration and Mesna, as per local policy. Patients will receive IV/PO cyclosporine according to local policy to begin on day 5 maintaining a trough level of 100-200 µg/L until day 90 before a subsequent taper in the absence of active GvHD. MMF will be given IV/PO according to local policy at a dose of 1g TDS to begin on day 5 and discontinued on day 35 without taper if there is no evidence of active GvHD. In adults weighing <55kg, MMF should be given at a lower dose of 0.75g IV/PO TDS. |
| Experimental arm (PTCy + Sirolimus + MMF) | Experimental | Drug: Cyclophosphamide, Drug: Sirolimus, Drug: Mycophenolate MofetilCyclophosphamide is given as an IV infusion of 50 mg/kg/day over 2 days (days 3 and 4; total dose 100 mg/kg) together with IV hydration and Mesna, as per local policy. Sirolimus will be initially given PO as a loading dose of 6 mg on day 5 followed by 2 mg daily; doses will be adjusted to maintain a trough level (in whole blood) of 8 to 14 ng/mL until day 60, thereafter 5-8 ng/mL until day 90. In the absence of active GvHD, the dose of sirolimus will be tapered from day 90. We recommend that the daily maintenance dose of sirolimus is reduced empirically to 0.5-1mg daily with concomitant treatment with a triazole anti-fungal agent. MMF will be given IV/O according to local policy at a dose of 1g TDS to begin on day 5 and discontinued on day 35 without taper if there is no evidence of active GvHD. In adults weighing <55kg, MMF should be given at a lower dose of 0.75g IV/PO TDS. |
Who may qualify
- Ages
- 16 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (20 listed)
- Availability of suitably matched unrelated donor (9/10 or 10/10)
- Planned to receive one of the following RIC protocols:
- Planned use of PBSCs for transplantation
- Planned allo-SCT for one of the following haematological malignancies:
- Age 16-70 years
Key exclusion criteria (15 listed)
- Use of any method of graft manipulation (excluding storage of future DLI)
- Use of alemtuzumab or any method of T cell depletion except those that are protocol-defined
- Known hypersensitivity to study drugs or history of hypersensitivity to rabbits
- Pregnant or lactating women
- Adults of reproductive potential not willing to use appropriate, highly effective, contraception during the specified period
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 |
|---|---|---|
| ThymoglobulinAlso: ATGGVHD prophylaxis | Drug | Control Arm Thymoglobulin + Cyclosporine + MMF |
| CyclophosphamidePost transplant cyclophosphamide strategy for GVHD prophylaxis | Drug | Experimental arm (PTCy + Cyclosporine + MMF), Experimental arm (PTCy + Sirolimus + MMF) |
| Cyclosporineimmunosuppressant | Drug | Control Arm Thymoglobulin + Cyclosporine + MMF, Experimental arm (PTCy + Cyclosporine + MMF) |
| Sirolimusimmunosuppressant | Drug | Experimental arm (PTCy + Sirolimus + MMF) |
| Mycophenolate MofetilAlso: MMFimmunosuppressant | Drug | Control Arm Thymoglobulin + Cyclosporine + MMF, Experimental arm (PTCy + Cyclosporine + MMF), Experimental arm (PTCy + Sirolimus + MMF) |
Primary outcome
GVHD-free, relapse-free survival
Time frame: at 1 year
GVHD assessment scoring will be performed as per the modified Glucksberg criteria (revised by MAGIC) and the National Institutes of Health (NIH) criteria. GvHD-free, relapse-free survival (GRFS) defined as the time from date of day 0 (defined as the day of stem cell infusion) to the date of first event or death from any cause. An event is defined as GvHD (both acute and chronic), relapse or progression. Patients who are alive and event free at the end of the trial will be censored at their date of last follow-up
19 secondary outcomes
Cumulative incidence of acute grade II-IV and III-IV GvHD
Time frame: at 1 year
Cumulative incidence of moderate and severe chronic GvHD
Time frame: at 1 year
Cumulative incidence of NRM
Time frame: at 1 year
Overall survival
Time frame: at 1 year
Progression-free survival
Time frame: at 1 year
Immune suppression-free survival
Time frame: at 1 year
Cumulative incidence of engraftment
Time frame: at 1 year
The incidence of full donor chimerism
Time frame: at 100 days
The cumulative incidence of infection requiring inpatient admission
Time frame: at 1 year
The number of inpatient days
Time frame: during first 12 months
The timing of mixed chimerism, persistent disease or relapse
Time frame: during first 12 months
Cumulative incidence of EBV-related PTLD
Time frame: during first 12 months
The number of doses of Rituximab administered for EBV reactivation
Time frame: during first 12 months
QoL measured by FACT-BMT questionnaire
Time frame: at baseline, 6 months and 12 months
Cumulative incidence of patients with haemorrhagic cystitis
Time frame: at 1 year
Cumulative incidence of CMV viremia and CMV end-organ disease
Time frame: 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) V4.0
Time frame: from the date of commencement of protocol defined treatment until 28 days after the administration of the last dose of IMP.
Tolerability defined to be the number of patients able to complete therapy as scheduled
Time frame: during first 12 months
Dose of Donor lymphocyte infusion (DLI) for mixed chimerism, persistent disease or relapse
Time frame: during first 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- Individual participant dataSharing planned: No
Related trials for Acute Myeloid Leukemia
RecruitingPhase 1
A Study of CHM-029 in Participants With NPM1 Mutated, KMT2A or NUP98 Rearranged AML
AML (Acute Myeloid Leukemia)
RecruitingPhase 2
Testing New Therapies for Patients With Acute Myeloid Leukemia Who Are Newly Diagnosed and Have Not Yet Started Treatment (A MyeloMATCH Treatment Trial)
Acute Myeloid Leukemia, Acute Myeloid Leukemia Arising From Previous Myelodysplastic/Myeloproliferative Neoplasm
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
RecruitingPhase 1/2
Venetoclax and CLAG-M for the Treatment of Acute Myeloid Leukemia and High-Grade Myeloid Neoplasms
Acute Biphenotypic Leukemia, Acute Myeloid Leukemia
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
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.
Ronjon Professor Chakraverty study director
Oxford Cancer & Haematology Centre, The Churchill Hospital, Old Road - Headington, Oxford, OX3 7LE Email: ronjon.chakraverty@ndcls.ox.ac.uk
17 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 Thymoglobulin, Cyclophosphamide and Cyclosporine in people with Acute Myeloid Leukemia and Acute Lymphoblastic Leukemia, run by University of Birmingham at 17 sites in United Kingdom.
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 20 inclusion and 15 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: looking for participants now, as of the sponsor's last update on 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United Kingdom. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact MoTD Trial (0121 371 7859, MoTD@trials.bham.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
GVHD-free, relapse-free survival (time frame: at 1 year). 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 May 2026.