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

Primary Purpose

Hematologic Malignancy

Status
Recruiting
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
CD45RA depleted donor lymphocyte infusion (DLI)
Sponsored by
University Hospital Tuebingen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hematologic Malignancy

Eligibility Criteria

8 Weeks - 65 Years (Child, Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • University Hospital Tuebingen, Department of Hematology, Oncology, Immunology and RheumatologyRecruiting
  • University Children's Hospital University Clinic TuebingenRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

Single-arm

Arm Description

Donor lymphocytes from allogeneic donors depleted of CD45RA lymphocytes.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Full Information

First Posted
July 4, 2023
Last Updated
July 13, 2023
Sponsor
University Hospital Tuebingen
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1. Study Identification

Unique Protocol Identification Number
NCT05943067
Brief Title
CD45RA Depleted DLI After TCRα/β Depleted Haploidentical HCT
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 27, 2023 (Actual)
Primary Completion Date
January 2028 (Anticipated)
Study Completion Date
December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital Tuebingen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hematologic Malignancy

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Single-arm
Arm Type
Other
Arm Description
Donor lymphocytes from allogeneic donors depleted of CD45RA lymphocytes.
Intervention Type
Biological
Intervention Name(s)
CD45RA depleted donor lymphocyte infusion (DLI)
Intervention Description
CD45RA depleted donor lymphocyte infusion (DLI) after TCRα/β depleted haploidentical HCT
Primary Outcome Measure Information:
Title
Phase I, dose escalation
Description
Safety and toxicity of CD45RA depleted DLI as defined by infusional toxicities and acute GVHD grad III-IV.
Time Frame
100 days
Title
Phase II, extension phase
Description
Acute graft-versus-host disease grade III-IV defined as GVHD occurring within 100 days after HCT
Time Frame
100 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
8 Weeks
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Wolfgang Bethge, MD, PhD
Phone
+49 7071 29-83176
Email
wolfgang.bethge@med.uni-tuebingen.de
First Name & Middle Initial & Last Name or Official Title & Degree
Peter Lang, MD, PhD
Phone
+49 7071 29-81386
Email
peter.lang@med.uni-tuebingen.de
Facility Information:
Facility Name
University Hospital Tuebingen, Department of Hematology, Oncology, Immunology and Rheumatology
City
Tuebingen,
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Wolfgang Bethge, MD, PhD
Phone
+49 (0) 7071 29-83176
Email
wolfgang.bethge@med.uni-tuebingen.de
First Name & Middle Initial & Last Name & Degree
Christoph Faul, MD, PhD
Phone
+49 (0) 7071 29-84087
Email
christoph.faul@med.uni-tuebingen.de
Facility Name
University Children's Hospital University Clinic Tuebingen
City
Tuebingen
ZIP/Postal Code
72076
Country
Germany
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Lang, MD, PhD
Phone
+49 7071 29-81386
Email
peter.lang@med.uni-tuebingen.de
First Name & Middle Initial & Last Name & Degree
Michaela Döring, MD, PhD
Phone
+49 7071 29-81386
Email
michaela.doering@med.uni-tuebingen.de

12. IPD Sharing Statement

Plan to Share IPD
No

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CD45RA Depleted DLI After TCRα/β Depleted Haploidentical HCT

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