M-2018-334 in Hematological Malignancies (HAPLO2022)

A Single-center Pilot Study Using TCRα/β and CD45RA Depleted Stem Cell Grafts From Haploidentical Donors for Hematopoietic Cell Transplantation in Adults(HAPLO2022)

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Hematological Malignancies
• Intervention / Treatment: Device: CliniMACS Prodigy® LP-TCRα/β-19-45RA (Trial Version)

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Premchand Pastula; Phone Number: +49 15144059503; Email: clinicaltrials_gov_ClinDev@miltenyibiotec.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HSC Recipient; PBSC grafts from haploidentical donors depleted of TCRaβ+ cells and CD45RA+ cells using CliniMACS Prodigy® will be infused into patients intravenously (IV)	Device: 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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of severe acute GVHD (aGVHD) till Day 100	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.	100 days after haploidentical hematopoietic cell transplantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Performance of the CliniMACS Prodigy® LP-TCRα/β-19-45RA(Trial Version)	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	Until Last Patient Last Visit(24 Months)
Incidence of acute GVHD (aGVHD) till six months post-transplantation	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	6 Months
Neutrophil Engraftment	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	Day 7
Platelet Engraftment	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.	Day 0
Chronic GVHD	Incidence and severity of chronic GVHD will be graded according to standard criteria for grading of chronic GVHD	1 Year
Non-relapse mortality (NRM)	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	Until Last patient last Visit(24 Months)
Infusion toxicity	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	15 minutes, 30 minutes, 2 hours, and 4 hours post infusion
Graft failure	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	30 Days
Overall survival (OS)	OS defined as time from transplantation to death or last follow-up and will be assessed at Day 100 and after 1 year	Day 100 and through study completion, an average of 1 year post transplantation
Disease-free survival (DFS)	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	Day 100 and through study completion, an average of 1 year post transplantation
GVHD/relapse-free survival (GRFS)	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.	GRFS will be assessed at Month 12 post transplantation
Immunosuppression-free survival (ISFS)	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.	Assessed at 1 year with a starting point at Day 45 post-transplantation
Relapse rate	Time to relapse will be calculated from the time of transplantation to evidence of relapse	12 Months
Hospitalization length/re-admission	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	Assessed at Day 30, Day 100 and at 12 Months post transplantation

Collaborators and Investigators

• Sponsor: Miltenyi Biomedicine GmbH
• Collaborators: City of Hope Comprehensive Cancer Center

Publications and helpful links

Helpful Links

• A multi-center phase I/II safety and feasibility study using CliniMACS TCRα/β and CD19 depleted stem cell grafts from haploidentical donors for hematopoietic progenitor cell transplantation in children and adults"

Study record dates

Study Major Dates

• Study Start (Estimated): April 30, 2024
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: December 5, 2023
• First Submitted That Met QC Criteria: January 15, 2024
• First Posted (Actual): January 25, 2024

Study Record Updates

• Last Update Posted (Actual): January 31, 2024
• Last Update Submitted That Met QC Criteria: January 29, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Hematologic Diseases; Neoplasms; Hematologic Neoplasms
• Other Study ID Numbers: M-2018-334

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes