Methods of T Cell Depletion Trial (MoTD)

NCT04888741 | Recruiting Phase 2 DMC

• 1 other identifier: RG_19-116
• Study Type: interventional
• Target: 400
• Locations: 1 country
• Sites: 17

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.

Conditions

Acute Myeloid Leukemia; Acute Lymphoblastic Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndromes; Non Hodgkin Lymphoma; Hodgkin Lymphoma; Multiple Myeloma; Chronic Myelogenous Leukemia; Myelofibrosis

Keywords

GvHD; Allogeneic Stem Cell Transplant; AML; MDS; CML; CMML; NHL; HL; Cyclophosphamide; Thymoglobulin; Cyclosporin; Sirolimus; Mycophenolate Mofetil

Outcome Measures

Primary Outcomes (1)

• 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

  at 1 year

Secondary Outcomes (19)

• 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

Study Arms (3)

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.

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.

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.

Drug: Cyclophosphamide; Drug: Sirolimus; Drug: Mycophenolate Mofetil

Interventions

Thymoglobulin DRUG

GVHD prophylaxis

Also known as: ATG

Control Arm Thymoglobulin + Cyclosporine + MMF

Cyclophosphamide DRUG

Post transplant cyclophosphamide strategy for GVHD prophylaxis

Experimental arm (PTCy + Cyclosporine + MMF); Experimental arm (PTCy + Sirolimus + MMF)

Cyclosporine DRUG

immunosuppressant

Control Arm Thymoglobulin + Cyclosporine + MMF; Experimental arm (PTCy + Cyclosporine + MMF)

Sirolimus DRUG

immunosuppressant

Experimental arm (PTCy + Sirolimus + MMF)

Mycophenolate Mofetil DRUG

immunosuppressant

Also known as: MMF

Control Arm Thymoglobulin + Cyclosporine + MMF; Experimental arm (PTCy + Cyclosporine + MMF); Experimental arm (PTCy + Sirolimus + MMF)

Eligibility Criteria

• Age: 16 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• 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

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• University of Birmingham: lead
• The Jon Moulton Charity Trust: collaborator
• IMPACT (funded by NHS Blood & Transplant, Anthony Nolan and Leukaemia UK): collaborator

Study Sites (17)

University Hospital of Wales

Cardiff, Wales, CF14 4XW, United Kingdom

RECRUITING

Queen Elizabeth Hospital

Birmingham, B15 2GW, United Kingdom

RECRUITING

Bristol Haematology and Oncology Centre

Bristol, BS2 8ED, United Kingdom

RECRUITING

Addenbrookes Hospital

Cambridge, CB2 0QQ, United Kingdom

RECRUITING

Queen Elizabeth Hospital Glasgow

Glasgow, G51 4TF, United Kingdom

RECRUITING

St Jame's University Hospital

Leeds, LS9 7TF, United Kingdom

RECRUITING

University College London Hospital

London, NW1 2BU, United Kingdom

RECRUITING

King's College Hospital

London, SE5 9RS, United Kingdom

RECRUITING

Hammersmith Hospital

London, W12 0HS, United Kingdom

RECRUITING

Manchester Royal Infirmary

Manchester, M13 9WL, United Kingdom

RECRUITING

The Christie

Manchester, M20 3QH, United Kingdom

RECRUITING

Freeman Hospital

Newcastle upon Tyne, NE7 7DN, United Kingdom

RECRUITING

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

RECRUITING

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

RECRUITING

Derriford Hospital

Plymouth, PL6 8DH, United Kingdom

RECRUITING

Royal Hallamshire Hospital

Sheffield, S102JF, United Kingdom

RECRUITING

The Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

RECRUITING

MeSH Terms

Conditions

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; Primary Myelofibrosis

Interventions

thymoglobulin; Cyclophosphamide; Cyclosporine; Sirolimus; Mycophenolic Acid

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Lymphoid; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Lymphoma; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Myeloproliferative Disorders

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Macrolides; Lactones; Caproates; Acids, Acyclic; Carboxylic Acids; Fatty Acids; Lipids

Study Officials

• Ronjon Professor Chakraverty

  Oxford Cancer & Haematology Centre, The Churchill Hospital, Old Road - Headington, Oxford, OX3 7LE Email: ronjon.chakraverty@ndcls.ox.ac.uk

  STUDY DIRECTOR

Central Study Contacts

MoTD Trial

CONTACT

0121 371 7859; MoTD@trials.bham.ac.uk

Andrea Dr Hodgkinson

CONTACT

0121 371 4365; A.Hodgkinson@bham.ac.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 3, 2021
• First Posted: May 17, 2021
• Study Start: February 22, 2021
• Primary Completion (Estimated): August 23, 2027
• Study Completion (Estimated): August 23, 2027
• Last Updated: May 5, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (17)