Methods of T cell Depletion Trial

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 - MoTD

Status

Not yet recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2019-002419-24-GB

Enrollment

400

Registered

2020-08-11

Start date

2020-09-23

Completion date

Unknown

Last updated

2020-10-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Acute Myeloid Leukaemia, Acute lymphoblastic leukaemia, Chronic myelomonocytic leukemia, Myelodysplastic syndromes, Non-Hodgkin lymphoma, Hodgkin lymphoma, Multiple myeloma, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia and Myelofibrosis MedDRA version: 21.1 Level: PT Classification code 10000880 Term: Acute myeloid leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) MedDRA version: 21.0 Level: LLT Classification code 10000844

Interventions

Product Name: Thymoglobulin Pharmaceutical Form: Powder for solution for infusion INN or Proposed INN: Thymoglobulin CAS Number: 308067-60-9 Concentration unit: mg milligram(s) Concentration type: eq

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • Availability of suitably matched unrelated donor (9/10 or 10/10) • Planned to receive one of the following reduced intensity conditioning(RIC) protocols: o Fludarabine-melphalan (Fludarabine 120-180mg/m^2; melphalan = 150mg/m^2) o BEAM or LEAM (carmustine 300mg/m^2 or lomustine 200mg/m^2 with: etoposide 800 mg/m^2; cytarabine 1600mg/m^2; melphalan 140mg/m^2) o Fludarabine-busulphan (Fludarabine 120-180mg/m^2; Busulphan = 8mg/kg PO or 6.4mg/kg IV) • Planned use of peripheral blood stem cells (PBSCs) for transplantation • Planned allo-SCT for one of the following haematological malignancies: o AML in complete remission (CR) o ALL in CR o CMML =65 years) yes F.1.3.1 Number of subjects for this age range 40

Exclusion criteria

Exclusion criteria: • Use of any method of graft manipulation (excluding storage of future donor lymphocyte infusion) • 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 50µmol/l o Aspartate transaminase (AST) or alanine transferase (ALT) >3 x upper limit of normal (ULN) • Participation in COSI or ALL-RIC trials

Design outcomes

Primary

Measure	Time frame
Main Objective: The principal objective of the trial is to determine GvHD-free, relapse-free survival (GRFS) of patients after receiving an experimental therapy compared with patients receiving a standard therapy.;Secondary Objective: The secondary objectives are to determine • 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 non-relapse mortality 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 donor lymphocyte infusion (DLI) for mixed chimerism, persistent disease or relapse • Cumulative incidence of EBV-related post-transplant lymphoproliferative disease (PTLD) • The number of doses of Rituximab administered for EBV reactivation during first 12 months • Quality of life measured by FACT-BMT questionnaire at baseline, 6 months and 12 months • Cumulative incidence of p;Primary end point(s): 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. ;Timepoint(s) of evaluation of this end point: Evaluated at 1 year	—

Measure

Time frame

Main Objective: The principal objective of the trial is to determine GvHD-free, relapse-free survival (GRFS) of patients after receiving an experimental therapy compared with patients receiving a standard therapy.;Secondary Objective: The secondary objectives are to determine • 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 non-relapse mortality 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 donor lymphocyte infusion (DLI) for mixed chimerism, persistent disease or relapse • Cumulative incidence of EBV-related post-transplant lymphoproliferative disease (PTLD) • The number of doses of Rituximab administered for EBV reactivation during first 12 months • Quality of life measured by FACT-BMT questionnaire at baseline, 6 months and 12 months • Cumulative incidence of p;Primary end point(s): 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. ;Timepoint(s) of evaluation of this end point: Evaluated at 1 year

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Secondary

Measure	Time frame
Secondary end point(s): The secondary objectives are to determine • • 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 ;Timepoint(s) of evaluation of this end point: Full donor chimerism evaluated at 100 days. Quality of life is evaluated at baseline, 6 months and at 12 months. Cumulative incidence of EBV-related PTLD and incidence of toxicities are evaluated throughout the trial. All other outcomes are evaluated at 1 year.	—

Measure

Time frame

Secondary end point(s): The secondary objectives are to determine • • 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 ;Timepoint(s) of evaluation of this end point: Full donor chimerism evaluated at 100 days. Quality of life is evaluated at baseline, 6 months and at 12 months. Cumulative incidence of EBV-related PTLD and incidence of toxicities are evaluated throughout the trial. All other outcomes are evaluated at 1 year.

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Countries

United Kingdom

Contacts

Public ContactRonjon Chakraverty

University College London

r.chakraverty@ucl.ac.uk02077940500

Outcome results

None listed

Source: EU CTR (via WHO ICTRP) · Data processed: Feb 4, 2026