CD45RA Depleted DLI After TCRα/β Depleted Haploidentical HCT (CD45RADLIHaplo)

University Hospital Tuebingen

Status and phase

Enrolling

Phase 2

Phase 1

Conditions

Hematologic Malignancy

Treatments

Biological: CD45RA depleted donor lymphocyte infusion (DLI)

Study type

Interventional

Funder types

Other

Identifiers

NCT05943067

CD45RADLIHaplo

Details and patient eligibility

About

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.

Full 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.

Enrollment

60 estimated patients

Sex

All

Ages

8 weeks to 65 years old

Volunteers

No Healthy Volunteers

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