Feasibility and Efficacy of Modified Donor Lymphocytes Infusion (CD45RA Negative Selected) After Haploidentical Transplantation With Post-transplantation Cyclophosphamide in Patients With Hematological Malignancies (ONC-2016-002).

NCT04687982 | Completed

• 1 other identifier: ONC-2016-002
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Interventional non-randomized trial. The duration of study will be 47 months. After haploidentical transplantation, patients without complications, mainly a GVHD ≥ grade 2, will receive mDLI. mDLI consists of donor lymphocytes infusion, harvested by apheresis the day before the day planned for infusion (or up to -7 days) as outpatient basis in the Day Hospital using a cell separator. The mDLIs preparation will be performed using a CliniMACS® (Miltenyi). A CD45RA-depletion Product LineTM from Miltenyi, including disposable reagents and devices, will be used. The planned number of mDLI is 3.

1. 1.Day +50 (+/- 7 days) from allogenic transplant, 1st mDLI 5x105CD3+/kg of recipient.
2. 2.4-6 weeks after 1st DLI, 2nd mDLI 1x106CD3+/kg of recipient.
3. 3.4-6 weeks after 2nd DLI, 3rd mDLI 5x106CD3+/kg of recipient. Day +50 was chosen as the starting time-point because at that time over two thirds of all acute GvHD episodes have already occurred in the absence of DLI (internal data, median +49 after bone marrow, +27 after peripheral stem cells); acute GvHD will thus be less likely a confounding factor. The choice of a maximum number of 3 mDLIs is based on the relatively narrow time interval where outcome improvement is expected, that is mainly in the first 6 months after haplo-HSCT. The planned doses are those mainly used in conventional DLIs during haplo-HSCT setting.

Conditions

Bone Marrow Transplant Infection; Bone Marrow Transplant Complications; Graft Vs Host Disease; Infection; Hematological Malignancy

Keywords

DLI; CD45+; donor lymphocytes infusion; mDLI; haploidentical transplantation; hematological malignancies

Outcome Measures

Primary Outcomes (4)

• to evaluate the efficacy of CD45RA-depleted haplo-DLIs (mDLIs) in the setting of patients receiving haplo-HSCT and PT-Cy, in terms of incidence of viral infections in the post-transplant period

  The primary endpoint is the rate of viral infections at day +100 after haplo-BMT.

  100 days

• to evaluate the impact of the modified DLIs on the occurrence of GvHD

  acute and chronic GvHD incidence

  1 year

• to evaluate the impact of the modified DLIs on relapse (graft-versus-tumor effect)

  relapse rate

  1 year

• to evaluate the impact of the modified DLIs on other types of infections;

  100-day cumulative incidence of other type of infections

  100 days

Study Arms (1)

mDLI infusion

EXPERIMENTAL

The planned number of mDLI is 3. 1. Day +50 (+/- 7 days) from allogenic transplant, 1st mDLI 5x105CD3+/kg of recipient. 2. 4-6 weeks after 1st DLI, 2nd mDLI 1x106CD3+/kg of recipient. 3. 4-6 weeks after 2nd DLI, 3rd mDLI 5x106CD3+/kg of recipient.

Biological: modified donor lymphocytes infusion (mDLI)

Interventions

modified donor lymphocytes infusion (mDLI) BIOLOGICAL

The planned number of mDLI is 3. 1. Day +50 (+/- 7 days) from allogenic transplant, 1st mDLI 5x105CD3+/kg of recipient. 2. 4-6 weeks after 1st DLI, 2nd mDLI 1x106CD3+/kg of recipient. 3. 4-6 weeks after 2nd DLI, 3rd mDLI 5x106CD3+/kg of recipient.

mDLI infusion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written, signed informed consent;
• Adult patients aged ≥18 years;
• Patients who underwent haploidentical transplantation with PT-Cy for haematological diseases since no more than 56 days;
• Patient who received myeloablative conditioning regimen, reduced intensity conditioning regimens, or non-myeloablative conditioning regimens;
• Availability of haploidentical donor (defined as those with ≥ 2 differences within one HLA haplotype) who agree to donate peripheral blood cells by leukapheresis and able to donate the day before the day planned for infusion (or up to - 7 days);
• GVHD/HVG prophylaxis consists in Cyclophosphamide: 50 mg/kg/day, day +3 and +4, Cyclosporine A: 3 mg/kg/day from day +5 to day +100, with tapering in 2 months Mycophenolate mofetil: 45 mg/kg/day, from day +5 to day +35.

You may not qualify if:

• Presence of grade 2-4 acute GVHD;
• Uncontrolled bacterial, viral or fungal infection;
• Aplasia defined as ANC less than 500/L;
• Evidence of disease progression after transplantation;
• Current participation in another clinical study.

Sponsors & Collaborators

• Istituto Clinico Humanitas: lead

Study Sites (1)

Istituto Clinico Humanitas

Rozzano, MI, 20089, Italy

Location

Related Publications (1)

• van Beek JJP, Puccio S, Di Vito C, De Paoli F, Zaghi E, Calvi M, Scarpa A, Peano C, Basso G, Cibella J, De Philippis C, Sarina B, Timofeeva I, Capizzuto R, Mannina D, Mineri R, Mariotti J, Crocchiolo R, Santoro A, Castagna L, Bramanti S, Mavilio D, Lugli E. Selected memory T cells infused post-haploidentical hematopoietic stem cell transplantation persist and hyperexpand. Blood Adv. 2023 Jul 25;7(14):3458-3468. doi: 10.1182/bloodadvances.2022007735.

  PMID: 36469095 DERIVED

MeSH Terms

Conditions

Graft vs Host Disease; Infections; Hematologic Neoplasms

Condition Hierarchy (Ancestors)

Immune System Diseases; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2020
• First Posted: December 29, 2020
• Study Start: November 13, 2018
• Primary Completion: January 8, 2020
• Study Completion: January 8, 2020
• Last Updated: December 29, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)