Risk-adapted Donor Lymphocyte Infusion After Allo-HSCT in Children With Hematologic Malignancy

NCT05009719 | Completed Phase 1

• 1 other identifier: hsct/dli
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Allo-hsct is potentially curative method of treatment for children and adolescent with hematologic malignancy. However, relapses of disease after allo-hsct occur up to 50% of patients and constitute the main cause of mortality after HSCT. Donor lymphocytes infusion (DLI) is a form of immunotherapy based on developement of reaction "graft versus from leukemia". This study evaluates the safety and efficacy of risk-adapted srtategy of DLI for prophylaxis and prevention posttransplant relapses in children and adolescent with hematologic malignancy.

Conditions

Hematologic Malignancy

Keywords

allo-HSCT; children; Donor LymphocyteI Infusion

Outcome Measures

Primary Outcomes (1)

• Relapse - free survival

  Estimate time to morphological relapse by Kaplan Mayer

  24 months

Secondary Outcomes (8)

• Overall survival analysis

  24 months

• Relapse rate analysis

  24 months

• Non-relapse mortality analysis

  24 months

• Incidence of acute GVHD grade II-IV

  125 days

• Incidence of moderate and severe chronic GVHD

  24 months

Study Arms (2)

Prophylactic

EXPERIMENTAL

The patients with high risk of relapse of disease and full donor chimerism after allo-HSCT without signs of the disease will be include in this group.

Biological: Prophylactic Donor lymphocytes infusions

Preventive

EXPERIMENTAL

The patients with persisted minimal residual disease or cytogenetic relapse after allo-HSCT will be include in this group.

Biological: Preventive Donor lymphocytes infusions

Interventions

Prophylactic Donor lymphocytes infusions BIOLOGICAL

Donor lymphocytes is taken by apheresis or dose of blood from allogeneic donor. After apheresis lymphocytes arel freezed for next using. DLI is transfused to patients IV using central venous access. Donor lymphocytes infusion start from D+60 - D+100 and continue with escalating doses every 1.5-3 months during first year after HSCT up to appearance of GVHD or signs of disease. First dose is 1\*10\*6 CD3+/kg. Subsequent doses increases by 0.5 log for haploidentical and unrelated donor and 1 log for sibling donor up to 1\*10\*8 CD3+/kg.

Prophylactic

Preventive Donor lymphocytes infusions BIOLOGICAL

Donor lymphocytes is taken by apheresis or dose of blood from allogeneic donor. After apheresis lymphocytes freeze for next using. DLI are transfused to patients IV using central venous access. Donor lymphocytes infusion continue with escalating doses every 1.5-3 months up to achieving MRD negative status or appearance of GVHD or signs of active disease. First dose is 1\*10\*6 CD3+/kg for patients without previous GVHD and 1\*10\*5 CD3+/kg for patients with previous GVHD. Subsequent doses increases by 0.5 log for haploidentical and unrelated donor and 1 log for sibling donor up to 1\*10\*8 CD3+/kg.

Preventive

Eligibility Criteria

• Age: 4 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age 4 months - 18 years old
• Diagnosis: acute lymphoblastic leukemia, acute myeloid leukemia, juvenile myelomonocytic leukemia, myelodysplastic syndrome, chronic myeloid leukemia
• Signed by legal representatives informed consent
• High risk disease ( for ALL - initial hyperleukocytosis\> 50x109 / L, T-cell ALL, hypodiploid karyotype, complex karyotype, MLL gene rearrangement, SIL-TAL deletion, primary resistent of the disease, early/very earle relapse, infant ALL; for AML patients - rearrangement of the MLL gene (except for t (1; 11) and t (9; 11) with M5 morphology), inv (3), t (3; 3), complex karyotype anomalies, t (8; 21 ) with trisomy 4, t (16; 21), monosomy 7, monosomy 5, M7 without t (1; 22), FLT3+, M6, t (7; 12), AML with multilineage dysplasia, p53 gene mutations, NUP98 translocations, primary resistent of the disease, early/very earle relapse infant AML, secondary AML; all juvenile myelomonocytic leukemia and myelodysplastic syndrome; allo-HSCT at 3 or more remission; persistence MRD before alloHSCT; allo-HSCT out of remission; persistence MRD after alloHSCT; cytogenetic relapse after alloHSCT )
• Donor chimerism=\>95%
• No poor graft function (haemoglobin concentration \< 100 g/L; neutrophils \< 1.0 × 10E + 9/L; and platelets \< 30 × 10E + 9/L on day ≥ 30 post transplant with complete donor chimerism and no graft-versus-host disease or relapse )
• ECOG 0-2 status
• Karnofsky/Lansky status \>30%

You may not qualify if:

• Uncontrolled bacterial or fungal infection at the time of enrollment
• Severe organ failure: creatinine more than 2 norms; ALT, AST more than 5 norms; bilirubin more than 1.5 norms
• Ejection fraction less than 50%
• Requirement for vasopressor support at the time of enrollment
• Somatic or psychiatric disorder making the patient unable to sign an informed consent
• Acute GVHD grade 3-4 in patient medical history
• Severe chronic GVHD in patient medical history

Sponsors & Collaborators

• St. Petersburg State Pavlov Medical University: lead

Study Sites (1)

RM Gorbacheva Research Institute

Saint Petersburg, 197022, Russia

Location

MeSH Terms

Conditions

Hematologic Neoplasms

Condition Hierarchy (Ancestors)

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Vice-director for science RM Gorbacheva Institute

Model Details: The patients in this study will be divided into 2 groups: prophylactic and preventive depending on indications. Patients without signs of disease with high risk of relapse will be included into prophylactic group. Patients with persistence minimal residual disease or cytogenetic relapse will be included into preventive group. Also, patients will move from the first group to second group, if the clinical status changes.

Study Record Dates

• First Submitted: August 16, 2021
• First Posted: August 17, 2021
• Study Start: April 1, 2021
• Primary Completion: April 1, 2023
• Study Completion: April 1, 2024
• Last Updated: June 25, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

RU (1)