M-2018-334 in Hematological Malignancies

Not Applicable

Not yet recruiting

• Conditions: Hematological Malignancies
• Interventions: Device: CliniMACS Prodigy® LP-TCRα/β-19-45RA (Trial Version)

• Registration Number: NCT06225050
• Lead Sponsor: Miltenyi Biomedicine GmbH

Brief Summary

This is a single-center, open-label, single-arm, pilot clinical study using TCRα/β and CD45RA depleted stem cell grafts from haploidentical donors for hematopoietic cell transplantation in 12 to 18 adult patients.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-12-05
• Study First Submitted QC: 2024-01-15
• Study First Posted: 2024-01-25
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-12
• Last Update Posted: 2025-05-14
• Study Start: 2025-10-31
• Primary Completion: 2028-10-31
• Study Completion: 2028-10-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• Patients, between 18 years to 75 years of age, with high-risk hematological malignancy requiring an allogeneic hematopoietic stem cell transplantation (AlloHCT), but do not have an HLA-matched donor available

Exclusion Criteria

• <3 months after preceding autologous transplantation or prior AlloHCT
• History of neurological impairment (active seizures, severe peripheral neuropathy, signs of leukoencephalopathy, active CNS infection)
• Active 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
• Cardiac dysfunction: adult patients ejection fraction <50% on echocardiography
• Patients with uncontrolled, >grade II hypertension (per Common Toxicity Criteria, CTC)
• Creatinine clearance <60 mL/min/1.73m2
• Respiratory failure necessitating supplemental oxygen
• HIV infection
• Positive anti-donor HLA antibody
• Treatment with checkpoint inhibitors in the period between 3 months prior to and 3 months after transplantation
• 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, myocardial infarction within 6 months prior to the study) 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
• Treatment with any investigational product within 4 weeks prior to study treatment

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
HSC Recipient	CliniMACS Prodigy® LP-TCRα/β-19-45RA (Trial Version)	PBSC grafts from haploidentical donors depleted of TCRaβ+ cells and CD45RA+ cells using CliniMACS Prodigy® will be infused into patients intravenously (IV)

Primary Outcome Measures

Name	Time	Method
Incidence of severe acute GVHD (aGVHD) till Day 100	100 days after haploidentical hematopoietic cell transplantation	Participants will be evaluated for the occurrence of aGVHD, grades III-IV in the first 100 days after transplantation and the time to occurrence of aGVHD, grades III-IV will be recorded. Severity of acute GVHD will be graded according to the CONSENSUS CRITERIA FOR GRADING OF ACUTE GVHD which has four Grades from Grade I to Grade IV. The higher the Score, the Worse the outcome.

Secondary Outcome Measures

Name	Time	Method
Platelet Engraftment	Day 0	Time to platelet engraftment will be defined as the first of three consecutive measurements of platelet count ≥20,000/µL without platelet transfusion support, starting from the day of the first stem cell transplantation.
Chronic GVHD	1 Year	Incidence and severity of chronic GVHD will be graded according to standard criteria for grading of chronic GVHD
Performance of the CliniMACS Prodigy® LP-TCRα/β-19-45RA(Trial Version)	Until Last Patient Last Visit(24 Months)	Performance of the CliniMACS Prodigy® LP-TCRα/β-19-45RA (Trial Version) will be assessed by calculating the log-depletion of TCRα/β+ and CD45RA+ cells
Hospitalization length/re-admission	Assessed at Day 30, Day 100 and at 12 Months post transplantation	Number of days that patients had to be hospitalized until discharge after transplantation, and after any subsequent occurrence of an event leading to re- hospitalization assessed
Incidence of acute GVHD (aGVHD) till six months post-transplantation	6 Months	Incidence of aGVHD, grade II-IV till six months post-transplantation will be evaluated. The maximum grade and the time to occurrence of acute GVHD will be recorded. Incidence and severity of acute GVHD will be graded according to the Consensus Criteria
Non-relapse mortality (NRM)	Until Last patient last Visit(24 Months)	NRM is defined as death occurring in a patient between the first day of conditioning and day of last assessment (all visits throughout the study), not due to disease relapse/recurrence
Graft failure	30 Days	Primary graft failure is defined as the failure to achieve an ANC ≥500 cells/µL by Day +30 in the setting of donor chimerism \< 5% using local methods
Relapse rate	12 Months	Time to relapse will be calculated from the time of transplantation to evidence of relapse
Neutrophil Engraftment	Day 7	Time to neutrophil engraftment will be defined as the first of three consecutive measurements of ANC ≥500/µL following conditioning regimen induced nadir, starting from the day of the first stem cell transplantation
Infusion toxicity	15 minutes, 30 minutes, 2 hours, and 4 hours post infusion	Maximum infusion toxicity on the days of transfusion will be evaluated by measuring the patient's blood pressure, heart rate, respiration rate and temperature one hour prior to the allograft infusion and then approximately 15 minutes, 30 minutes, 2 hours, and 4 hours post infusion
Overall survival (OS)	Day 100 and through study completion, an average of 1 year post transplantation	OS defined as time from transplantation to death or last follow-up and will be assessed at Day 100 and after 1 year
Disease-free survival (DFS)	Day 100 and through study completion, an average of 1 year post transplantation	DFS is defined as the minimum time to relapse/recurrence, to death or to the last follow-up, from the time of transplantation and will be assessed at Day 100 and after 1 year
GVHD/relapse-free survival (GRFS)	GRFS will be assessed at Month 12 post transplantation	An event is defined as grade III-IV acute GVHD, moderate to severe chronic GVHD, disease relapse, or death by any cause. GRFS will be assessed at 1 year.
Immunosuppression-free survival (ISFS)	Assessed at 1 year with a starting point at Day 45 post-transplantation	Defined as being alive, relapse-free and off immunosuppressive therapy and will be assessed at 1 year with a starting point at Day 45 post-transplantation. Immune suppression is defined as any systemic agents used to control or suppress GVHD.