A multicenter phase I/II study for the use of infusions of donor memory T cells after haploidentical stem cell transplantation with TCRaß and CD19-depleted stem cells.

A multi-center phase I/II trial of memory T cell donor lymphocyte infusions after transplantation of CliniMACS TCRa/ß and CD19 depleted stem cell grafts from haploidentical donors for hematopoietic cell transplantation

Status

Active, not recruiting

Phases

Phase 2

Study type

Interventional

Source

EU CTR

Registry ID

EUCTR2022-001080-27-DE

Enrollment

Registered

2022-04-12

Start date

2022-11-23

Completion date

Unknown

Last updated

2023-11-27

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

Conditions

Patients suffering from hematological malignancies and eligible for haploidentical allogeneic stem cell transplantation. Patients will be included prior start of conditioning for SCT. Inclusion criteria for IMP infusions will be rechecked on day 30 after SCT. MedDRA version: 21.1 Level: LLT Classification code 10066481 Term: Hematological malignancy System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Interventions

Product Name: Allogeneic T-cell concentrate CD45RA depleted Pharmaceutical Form: Solution for infusion

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: • Adult and paediatric patients with hematological malignancies in complete remission (CR), partial remission (PR) or with stable disease - Acute myeloid leukemia (AML): Patients with high-risk AML in CR1 Patients with relapsed or primary therapy-refractory AML - Acute lymphoid leukemia (ALL): Patients with high-risk ALL in CR1 Patients with relapsed or primary refractory ALL - Hodgkin’s disease: Patients with relapsed or primary refractory Hodgkin’s disease - Non-Hodgkin’s lymphoma: Patients with relapsed or primary refractory Non-Hodgkin’s lymphoma - Myelodysplastic Syndrome (MDS)/ Myeloproliferative Syndrome (MPS): Patients with refractory MDS/MPS - Multiple myeloma (MM): Patients with relapsed or refractory multiple myeloma • No signs of acute GVHD on day 30 (day of infusion of DLI/IMP) after haploidentical HHCT • Patients aged =1 year to =65 years For safety reasons, dose escalation part within this study should only be performed for adults and older children (>6 years). The second part of the study, with already evaluated safe dose level, also younger children (=1 year) can be included. Are the trial subjects under 18? yes Number of subjects for this age range: 2 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range

Exclusion criteria

Exclusion criteria: • Age >65 years or 2 mg/dL and elevation of transaminases higher than 400 U/L • Chronic active viral hepatitis • Ejection fraction grade II hypertension by CommonToxicity Criteria (CTC) • Creatinine clearance below threshold defined for stem cell transplantation according to local clinical standard • Respiratory failure necessitating supplemental oxygen • HIV infection • Female patients who are pregnant or breast feeding, or adults of reproductive potential not willing to use an effective method of birth control during study treatment and for at least 12 months thereafter Note: Women of childbearing potential must have a negative serum pregnancy test at study entry. • Concurrent severe or uncontrolled medical disease (e.g. uncontrolled diabetes, congestive heart failure, myocardial infarction within 6 months prior to the study, unstable and uncontrolled hypertension, chronic renal disease, or active uncontrolled infection) which by assessment of the treating physician could compromise participation in the study • Patients with a history of psychiatric illness or a condition which could interfere with their ability to understand the requirements of the study (this includes alcoholism/drug addiction) • Patients unwilling or unable to comply with the protocol or unable to give informed consent

Design outcomes

Primary

Measure	Time frame
Main Objective: Phase I dose escalation: Safety and toxicity of CD45RA depleted DLI as defined by infusional toxicities and acute GVHD grad III-IV. - Infusional toxicity: maximum toxicity on the days of transfusion evaluated by measuring vital signs prior to and at different times after transfusion Acute graft-versus-host disease grade III–IV defined as GVHD occurring within 100 days after SCT Severity graded according to Seattle (Glucksberg) criteria: - Incidence of acute GVHD grade III-IV - Time until occurrence of acute GVHD grade III-IV Phase II extension phase: - Number of CD3+/CD4+ T cells - Immune reconstitution on Day +100 ;Secondary Objective: - Incidence of acute graft versus host disease GVHD) grade II-IV until Day 100 post transplantation - Incidence and severity of chronic GVHD after 1 year - Incidence of NRM after 1 year - Overall survival at Day 100 and after 1 year - Disease-free survival at Day 100 and after 1 year - Incidence of relapse at Day 100 and after 1 year - Number and percentage of patients who are off immunosuppression at one year post transplant - Donor chimerism - Reconstitution of T, B, NK and T regulatory (Treg) cell subsets by immune cell phenotyping - TCR V ß Spectrotyping , TREC analysis - T-cell activity - Infections: Incidence of CMV, ADV, EBV and aspergillus, as well as other viral, bacterial and fungal infections - Incidence, severity and type of adverse events/serious adverse events ;Primary end point(s): Assessment of safety and tolerability of CD45RA depleted DLI will be measured by acute infusional toxicity such as allergic reactions and AEs >4 but also as described by the incidence of acute graft-versus-host disease grade III–IV defined as GVHD occurring within 100 days after HCT. The primary endpoint for part 2 of the study will be the immune reconstitution on Day +100 as assessed as by the log count of CD4+ T cells. ;Timepoint(s) of evaluation of this end point: The main analysis will be presen	—

Measure

Time frame

Main Objective: Phase I dose escalation: Safety and toxicity of CD45RA depleted DLI as defined by infusional toxicities and acute GVHD grad III-IV. - Infusional toxicity: maximum toxicity on the days of transfusion evaluated by measuring vital signs prior to and at different times after transfusion Acute graft-versus-host disease grade III–IV defined as GVHD occurring within 100 days after SCT Severity graded according to Seattle (Glucksberg) criteria: - Incidence of acute GVHD grade III-IV - Time until occurrence of acute GVHD grade III-IV Phase II extension phase: - Number of CD3+/CD4+ T cells - Immune reconstitution on Day +100 ;Secondary Objective: - Incidence of acute graft versus host disease GVHD) grade II-IV until Day 100 post transplantation - Incidence and severity of chronic GVHD after 1 year - Incidence of NRM after 1 year - Overall survival at Day 100 and after 1 year - Disease-free survival at Day 100 and after 1 year - Incidence of relapse at Day 100 and after 1 year - Number and percentage of patients who are off immunosuppression at one year post transplant - Donor chimerism - Reconstitution of T, B, NK and T regulatory (Treg) cell subsets by immune cell phenotyping - TCR V ß Spectrotyping , TREC analysis - T-cell activity - Infections: Incidence of CMV, ADV, EBV and aspergillus, as well as other viral, bacterial and fungal infections - Incidence, severity and type of adverse events/serious adverse events ;Primary end point(s): Assessment of safety and tolerability of CD45RA depleted DLI will be measured by acute infusional toxicity such as allergic reactions and AEs >4 but also as described by the incidence of acute graft-versus-host disease grade III–IV defined as GVHD occurring within 100 days after HCT. The primary endpoint for part 2 of the study will be the immune reconstitution on Day +100 as assessed as by the log count of CD4+ T cells. ;Timepoint(s) of evaluation of this end point: The main analysis will be presen

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Secondary

Measure	Time frame
Secondary end point(s): Secondary endpoints include the rate of NRM, chronic GVHD, reconstitution and functionality of relevant cells of the immune system (T, B and NK cell subsets as well as T regulatory cells), relapse rate, overall and disease-free at 1 year after transplantation. ;Timepoint(s) of evaluation of this end point: The main analysis will be presented after completion of the 100 days post-transplantation visit, i.e. when all patients have either completed the 100 days period after transplantation, are lost to follow-up or have died within this period. Additional analyses will be done on the 1-year follow-up data, i.e. when all patients have completed the 1-year period after transplantation, are lost to follow-up or have died within these periods.	—

Measure

Time frame

Secondary end point(s): Secondary endpoints include the rate of NRM, chronic GVHD, reconstitution and functionality of relevant cells of the immune system (T, B and NK cell subsets as well as T regulatory cells), relapse rate, overall and disease-free at 1 year after transplantation. ;Timepoint(s) of evaluation of this end point: The main analysis will be presented after completion of the 100 days post-transplantation visit, i.e. when all patients have either completed the 100 days period after transplantation, are lost to follow-up or have died within this period. Additional analyses will be done on the 1-year follow-up data, i.e. when all patients have completed the 1-year period after transplantation, are lost to follow-up or have died within these periods.

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Countries

Germany

Contacts

Public ContactProjectmanagement

Zentrum fuer klinische Studien (ZKS)

zks-pm@med.uni-tuebingen.de0049070712985635

Outcome results

None listed

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