Prophylactic CD45RA-depleted DLI After Haploidentical Transplantation/RIC

A Phase I Clinical Trial Assessing Prophylactic Donor CD45RA-depleted Lymphocyte Infusions Into Patients Transplanted With Stem Cell Grafts From Haploidentical Donors After Reduced Intensity Conditioning

To assess safety of prophylactic escaladed dose of T naïve depleted (CD45RA depleted donor lymphocyte infusion, in patients with malignant hemopathie who received an allogeneic stem cell transplant from an haplo-identical donor, after a reduced intensity conditionning regiment.

Study Overview

• Status: Not yet recruiting
• Conditions: Hematologic Malignancy; Haplo-identical Stem Cell Transplantation
• Intervention / Treatment: Other: CD45RAneg cells, prepared from mononuclear cell leukapheresis by CliniMACS® technology

Detailed Description

Primary Objective is to determine whether the administration of prophylactic CD45RAneg (CD45RAneg) memory/effector T lymphocytes is feasible and safe in the early post-transplant period for patients with haploidentical transplant and RIC conditioning.

Donor lymphocytes are isolated from the original donor by non-mobilized mononuclear cell leukapheresis. Repetitive intravenous infusions (up to 3) of escalating doses of CD45RAneg cells, prepared from the leukapheresis by CliniMACS® technology (CD45RA-depletion), storage in vapor nitrogen.

Escalating doses of CD45RAneg cells, for patients with haploidentical graft, intervals of 6-8 weeks, if GvHD is absent starting ≥ 4 weeks from the day of transplantation.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients who received a stem cell graft from a haploidentical donor after RIC for hematologic malignancies
• Written informed consent of patient and donor obtained

Exclusion Criteria:

• Participant taking Prednisone (or equivalent steroid)
• Participant taking Prednisone (or equivalent steroid)
• Participant taking Mycophenolate Mofetil
• Participant taking Cyclosporine/tacrolimus at therapeutic blood levels
• Progressive hematologic malignancy before transplant
• Second allogeneic transplant
• Acute GvHD ≥ grade 2
• Chronic moderate or severe GvHD (NIH consensus criteria)
• Hematologic or molecular relapse of the primary malignancy requiring chemotherapy or unmanipulated DLI (receiving prophylactic antileukemic agent, eg TKI, is not an exclusion criteria)
• Donor aberrant CD45RA expression due to a polymorphism in CD45 gene
• Participation in another interventional clinical trial within 30 days prior to inclusion
• Pregnant or nursing women. Sexually active women with childbearing potential as well as sexually active male patients who are unwilling to use an effective method of contraception during participation in the study from time of inclusion until 2 months after last dose of CD45RAneg DLI infusion
• Inability to follow the procedures of the study, including, but not limited to, language problems, psychological disorders, dementia

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: Arm 1; Prophylactic CD45RA-depleted DLI	Other: CD45RAneg cells, prepared from mononuclear cell leukapheresis by CliniMACS® technology; CD45RAneg cells, prepared from mononuclear cell leukapheresis by CliniMACS® technology

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
acute transfusion reaction (CTCAE ≥ 2)	acute transfusion reaction after each DLI infusion (CTCAE ≥ 2)	24 hours after each CD45RA neg DLI infusion
acute GvHD grade II-IV	acute GvHD grade II-IV measured with MAGIC score	within 8 weeks after each CD45RAneg DLI infusion

Collaborators and Investigators

• Sponsor: University Hospital, Geneva

Study record dates

Study Major Dates

• Study Start (Anticipated): October 15, 2021
• Primary Completion (Anticipated): June 2, 2026
• Study Completion (Anticipated): December 2, 2026

Study Registration Dates

• First Submitted: July 9, 2021
• First Submitted That Met QC Criteria: October 1, 2021
• First Posted (Actual): October 4, 2021

Study Record Updates

• Last Update Posted (Actual): October 4, 2021
• Last Update Submitted That Met QC Criteria: October 1, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Hematologic Diseases; Hematologic Neoplasms
• Other Study ID Numbers: Cd45RA depleted DLI

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: No