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).

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. 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. 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.

Stopping infusion rules:

If GvHD ≥ Grade 2 or relapse occurs, mDLIs will not be administered at any time and patient will be permanently discontinued from treatment.

If any severe adverse event (SAE) occurs after the first mDLI, the administration of mDLI will be interrupted for a maximum of 6 weeks until event resolution. If the SAE does not resolve after 6 weeks from last mDLI infusion, patient will be permanently discontinued. At any time, the experimental treatment may be stopped according to clinical judgement or patient's willing.

Study Overview

• Status: Completed
• Conditions: Infection; Graft Vs Host Disease; Hematological Malignancy; Bone Marrow Transplant Complications; Bone Marrow Transplant Infection
• Intervention / Treatment: Biological: modified donor lymphocytes infusion (mDLI)

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • MI
    • Rozzano, MI, Italy, 20089
      • Istituto Clinico Humanitas

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:

1. Written, signed informed consent;
2. Adult patients aged ≥18 years;
3. Patients who underwent haploidentical transplantation with PT-Cy for haematological diseases since no more than 56 days;
4. Patient who received myeloablative conditioning regimen, reduced intensity conditioning regimens, or non-myeloablative conditioning regimens;
5. 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);
6. 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.

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• 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: mDLI infusion; The planned number of mDLI is 3.; Day +50 (+/- 7 days) from allogenic transplant, 1st mDLI 5x105CD3+/kg of recipient.; 4-6 weeks after 1st DLI, 2nd mDLI 1x106CD3+/kg of recipient.; 4-6 weeks after 2nd DLI, 3rd mDLI 5x106CD3+/kg of recipient.	Biological: modified donor lymphocytes infusion (mDLI); The planned number of mDLI is 3.; Day +50 (+/- 7 days) from allogenic transplant, 1st mDLI 5x105CD3+/kg of recipient.; 4-6 weeks after 1st DLI, 2nd mDLI 1x106CD3+/kg of recipient.; 4-6 weeks after 2nd DLI, 3rd mDLI 5x106CD3+/kg of recipient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Istituto Clinico Humanitas

Study record dates

Study Major Dates

• Study Start (Actual): November 13, 2018
• Primary Completion (Actual): January 8, 2020
• Study Completion (Actual): January 8, 2020

Study Registration Dates

• First Submitted: December 10, 2020
• First Submitted That Met QC Criteria: December 24, 2020
• First Posted (Actual): December 29, 2020

Study Record Updates

• Last Update Posted (Actual): December 29, 2020
• Last Update Submitted That Met QC Criteria: December 24, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: hematological malignancies; DLI; haploidentical transplantation; CD45+; donor lymphocytes infusion; mDLI
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Site; Disease Attributes; Hematologic Diseases; Neoplasms; Hematologic Neoplasms; Infections; Communicable Diseases; Graft vs Host Disease
• Other Study ID Numbers: ONC-2016-002

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