CD45RA Depleted DLI After TCRα/β Depleted Haploidentical HCT

Hematologic Malignancy Clinical Trial

— CD45RADLIHaplo  

Official title:

A Multi-center Phase I/II Trial of Memory T Cell Donor Lymphocyte Infusions After Transplantation of CliniMACS® TCRα/β and CD19 Depleted Stem Cell Grafts From Haploidentical Donors for Hematopoietic Cell Transplantation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05943067
• Other study ID #: CD45RADLIHaplo
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: April 27, 2023
• Est. completion date: December 2028

Study information

• Verified date: July 2023
• Source: University Hospital Tuebingen
• Contact: Wolfgang Bethge, MD, PhD
• Phone: +49 7071 29-83176
• Email: wolfgang.bethge[@]med.uni-tuebingen.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2028
• Est. primary completion date: January 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Weeks to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Malignancy
• Hematologic Neoplasms

Intervention

Biological:
• CD45RA depleted donor lymphocyte infusion (DLI)
CD45RA depleted donor lymphocyte infusion (DLI) after TCRa/ß depleted haploidentical HCT

Locations

Country	Name	City	State
Germany	University Children's Hospital University Clinic Tuebingen	Tuebingen
Germany	University Hospital Tuebingen, Department of Hematology, Oncology, Immunology and Rheumatology	Tuebingen,

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital Tuebingen

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Phase I, dose escalation	Safety and toxicity of CD45RA depleted DLI as defined by infusional toxicities and acute GVHD grad III-IV.	100 days
Primary	Phase II, extension phase	Acute graft-versus-host disease grade III-IV defined as GVHD occurring within 100 days after HCT	100 days