A Phase 2 interventional study of Thymoglobulin and Cyclophosphamide in Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia and Chronic Myelomonocytic Leukemia, sponsored by University of Birmingham. Recruiting at 17 sites in United Kingdom. Open to participants aged 16 Years to 70 Years. Per ClinicalTrials.gov, last updated 2026-05-05.
Sponsored by University of Birmingham · Phase 2, Interventional, and Prevention
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.
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:
Secondary Outcome Measures:
Exploratory Outcome Measures:
The scientific research will address the following questions:
Patient Population
Adults considered suitable for an allo-SCT with the following haematological malignancies will be recruited to this trial:
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
3,667 studies on the registry are indexed under Leukemia, Myeloid, Acute; 816 are open to participants now.
This study's planned enrollment of 400 is above the median of 40 across 3,005 interventional studies indexed under Leukemia, Myeloid, Acute.
Browse Leukemia, Myeloid, Acute studies →University of Birmingham is the lead sponsor of 182 studies on the registry; 29 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Planned to receive one of the following RIC protocols:
Planned allo-SCT for one of the following haematological :
Exclusion Criteria:
Organ dysfunction defined as:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Reproductive potential
Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.
Criteria about it usually ask for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Postmenopausal
Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Life expectancy
The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Bilirubin
A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.
Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ALT and AST (liver enzymes)
Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.
Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Thymoglobulin · Drug: Cyclosporine · Drug: Mycophenolate Mofetil
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.
Drug: Cyclophosphamide · Drug: Cyclosporine · Drug: Mycophenolate Mofetil
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.
Drug: Cyclophosphamide · Drug: Sirolimus · Drug: Mycophenolate Mofetil
GVHD prophylaxis
Also known as: ATG
Post transplant cyclophosphamide strategy for GVHD prophylaxis
immunosuppressant
immunosuppressant
immunosuppressant
Also known as: MMF
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
Time frame: at 1 year
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
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: 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.
Time frame: 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.
Time frame: 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
Time frame: at 1 year
The number of inpatient days
The sum of inpatients days
Time frame: 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
Time frame: during first 12 months
Cumulative incidence of EBV-related PTLD
Measured by blood sample, EBV PCR testing.
Time frame: 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
Time frame: 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.
Time frame: 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
Time frame: 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
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
. 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.
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
Tolerability defined to be the number of patients able to complete therapy as scheduled (excluding any patients who discontinued treatment due to toxicities
Time frame: 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
Time frame: during first 12 months
Plan to share: No
No publications or documents are linked to this record.
Started Feb 2021 (actual). Primary completion is estimated for Aug 2027, 78 months after the start.
Of 385 non-industry phase 2 interventional studies under Leukemia, Myeloid, Acute, half reached primary completion within 67 months of starting (the median), counting those still running; a quarter within 40 and three quarters within 108. This study's planned 78 months is above that.
Counting every sponsor, half of 442 studies reached it within 60 months; a quarter within 38 and three quarters within 104.
How these figures are worked out, and which studies are left out of them.
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Studies of the drugs tested here: Cyclophosphamide · Cyclosporine · Sirolimus