CD45RA Depleted DLI After TCRα/β Depleted Haploidentical HCT

NCT ID: NCT05943067

Last Updated: 2025-04-27

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-04-27
• Study Completion Date: 2028-12-31

Brief Summary

The purpose of this clinical trial is to examine safety and toxicity of CD45RA depleted donor lymphocyte infusion (DLI) after transplantation of TCRα/β/CD19 depleted peripheral blood stem cells.

Detailed Description

Patients will undergo routine reduced intensity conditioning regimen and intravenous infusion of T-cell receptor alpha/beta (TCRα/β)/CD19 depleted peripheral blood stem cells (not content of clinical trial).

If no graft-versus-host disease (GVHD) occurs, patients receive the trial-related memory T cell donor lymphocyte infusion (DLI) on Day 30 after transplantation.

In a dose finding part (phase I) escalating doses will be applied in cohorts of three (three plus three design) patients with a maximum of 18 patients for three dose levels (dose level 1-3). A fourth lower dose level (dose level 0) is started, if >=2 out of 6 patients with dose level 1 develop aGVHD III/IV. The maximum tolerated dose (MTD) will be used for the confirmatory part (phase II) of the study.

Conditions

Hematologic Malignancy

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Single-arm

Donor lymphocytes from allogeneic donors depleted of CD45RA lymphocytes.

Group Type: OTHER

CD45RA depleted donor lymphocyte infusion (DLI)

Intervention Type: BIOLOGICAL

CD45RA depleted donor lymphocyte infusion (DLI) after TCRα/β depleted haploidentical HCT

Interventions

CD45RA depleted donor lymphocyte infusion (DLI)

CD45RA depleted donor lymphocyte infusion (DLI) after TCRα/β depleted haploidentical HCT

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

Adult and pediatric 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 first complete remission (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

Exclusion Criteria

• Age >65 years or <8 weeks
• Patients with progressive disease prior hematopoietic cell transplantation (HCT)
• <3 months after preceding HCT
• Treatment with T-cell or Interleukin-2 (IL-2) targeted medication (e.g. alemtuzumab, basiliximab) within 60 days prior to study product infusion
• Treatment with prednisolone at >2 mg/kg/day (or equivalent dosing of alternative glucocorticosteroids) at time of study product infusion.
• Known allergy/hypersensitivity to any component of the study product
• Treatment with another investigational drug within one month before inclusion
• History of neurological impairment (active seizures, severe peripheral neuropathy, signs of leukoencephalopathy, active Central Nervous System (CNS) infection) Note: For patients with heavy pretreatment with irradiation or intrathecal chemotherapy pre-transplant CNS MRI and neurological consultation are mandatory.
• Fungal infections with radiological and clinical progression
• Liver function abnormalities with bilirubin >2 mg/dL and elevation of transaminases higher than 400 U/L
• Chronic active viral hepatitis
• Ejection fraction <40% or Shortening fraction <20% on echocardiography. Patients with > grade II hypertension by Common Toxicity 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

• Minimum Eligible Age: 8 Weeks
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Tuebingen

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University Children's Hospital University Clinic Tuebingen

Tübingen, , Germany

Site Status: RECRUITING

University Hospital Tuebingen, Department of Hematology, Oncology, Immunology and Rheumatology

Tübingen, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Wolfgang Bethge, MD, PhD

Role: CONTACT

wolfgang.bethge@med.uni-tuebingen.de

+49 7071 29-83176

Peter Lang, MD, PhD

Role: CONTACT

peter.lang@med.uni-tuebingen.de

+49 7071 29-81386

Facility Contacts

Peter Lang, MD, PhD

Role: primary

peter.lang@med.uni-tuebingen.de

+49 7071 29-81386

Michaela Döring, MD, PhD

Role: backup

michaela.doering@med.uni-tuebingen.de

+49 7071 29-81386

Wolfgang Bethge, MD, PhD

Role: primary

wolfgang.bethge@med.uni-tuebingen.de

+49 (0) 7071 29-83176

Christoph Faul, MD, PhD

Role: backup

christoph.faul@med.uni-tuebingen.de

+49 (0) 7071 29-84087

Other Identifiers

CD45RADLIHaplo

Identifier Type: -

Identifier Source: org_study_id