M-2018-334 in Hematological Malignancies

Hematological Malignancies Clinical Trial

— HAPLO2022  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06225050
• Other study ID #: M-2018-334
• Status: Not yet recruiting
• Phase: N/A
• Start date: April 30, 2024
• Est. completion date: April 30, 2027

Study information

• Verified date: January 2024
• Source: Miltenyi Biomedicine GmbH
• Contact: Premchand Pastula
• Phone: +49 15144059503
• Email: clinicaltrials_gov_ClinDev[@]miltenyibiotec.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 18
• Est. completion date: April 30, 2027
• Est. primary completion date: April 30, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Neoplasms
• Hematological Malignancies
• Neoplasms

Intervention

Device:
• CliniMACS Prodigy® LP-TCRa/ß-19-45RA (Trial Version)
PBSC grafts from haploidentical donors depleted of TCRaß+ cells and CD45RA+ cells using CliniMACS Prodigy® will be infused into patients intravenously (IV)

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Miltenyi Biomedicine GmbH	City of Hope Comprehensive Cancer Center

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Performance of the CliniMACS Prodigy® LP-TCRa/ß-19-45RA(Trial Version)	Performance of the CliniMACS Prodigy® LP-TCRa/ß-19-45RA (Trial Version) will be assessed by calculating the log-depletion of TCRa/ß+ and CD45RA+ cells	Until Last Patient Last Visit(24 Months)
Secondary	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
Secondary	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
Secondary	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
Secondary	Chronic GVHD	Incidence and severity of chronic GVHD will be graded according to standard criteria for grading of chronic GVHD	1 Year
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Relapse rate	Time to relapse will be calculated from the time of transplantation to evidence of relapse	12 Months
Secondary	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

External Links

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