Infusion of modified donor immune cells after stem cell transplant for blood cancers

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

This study is testing a new way to use modified immune cells after a stem cell transplant to see if it helps people with blood cancers without causing serious side effects.

Quick facts

• Phase: Phase1; Phase2
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 8 Weeks to 65 Years
• Sex: All
• Sponsor: University Hospital Tuebingen (Academic / other)
• Drugs / interventions: alemtuzumab, basiliximab, chemotherapy
• Locations: 2 sites (Tübingen and 1 other locations)
• Trial ID: NCT05943067 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the safety and toxicity of CD45RA depleted donor lymphocyte infusion (DLI) following the transplantation of TCRα/β/CD19 depleted peripheral blood stem cells in patients with hematologic malignancies. Participants will undergo a reduced intensity conditioning regimen before receiving the stem cell infusion. If no severe graft-versus-host disease (GVHD) occurs, patients will receive the DLI on Day 30 post-transplant. The trial includes a dose-finding phase (Phase I) to determine the maximum tolerated dose, which will then be used in the confirmatory Phase II part of the study.

Who should consider this trial

Good fit: Ideal candidates include adults and children with hematologic malignancies in complete or partial remission or with stable disease.

Not a fit: Patients over 65 years old or those with progressive disease prior to hematopoietic cell transplantation may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could improve outcomes for patients with hematologic malignancies by enhancing immune response without increasing the risk of GVHD.

How similar studies have performed: Other studies have shown promise with similar approaches, but this specific method is still being evaluated for its effectiveness.

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

Where this trial is running

Tübingen and 1 other locations

• University Children's Hospital University Clinic Tuebingen — Tübingen, Germany (Recruiting)
• University Hospital Tuebingen, Department of Hematology, Oncology, Immunology and Rheumatology — Tübingen, Germany (Recruiting)

Study contacts

• Study coordinator: Wolfgang Bethge, MD, PhD

Conditions Hematologic Malignancy