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.

Phase 1

• 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: 21.1Level: LLTClassification code 10066481Term: Hematological malignancySystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2022-001080-27-DE
• Lead Sponsor: niversity Hospital Tuebingen

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-04-12
• Last Update Posted: 27 November 2023

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 60

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

• Age >65 years or <1 year
• Patients with progressive disease prior HCT
• <3 months after preceding hematopoietic cell transplantation (HCT)
• Treatment with T-cell or IL-2 targeted medication (e.g. alemtuzumab, basiliximab) within 60 days prior to study product infusion
• Continuous treatment with prednisolone (or alternative glucocorticosteroid e.g. dexamethasone, short term use =3 days for other indication as GVHD allowed) within two weeks prior study product infusion (DLI).
• 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 leukencephalopathy, active CNS infection)
Note: For patients with HLH or Malignant Osteopetrosis or other 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 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified