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

Phase 1

Completed

• Conditions: Hematologic Malignancy
• Interventions: Biological: Prophylactic Donor lymphocytes infusions; Biological: Preventive Donor lymphocytes infusions

• Registration Number: NCT05009719
• Lead Sponsor: St. Petersburg State Pavlov Medical University

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2021-04-01
• Study First Submitted: 2021-08-16
• Study First Submitted QC: 2021-08-16
• Study First Posted: 2021-08-17
• Primary Completion: 2023-04-01
• Study Completion: 2024-04-01
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-23
• Last Update Posted: 2024-06-25

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• 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%

Exclusion Criteria

• 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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prophylactic	Prophylactic Donor lymphocytes infusions	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.
Preventive	Preventive Donor lymphocytes infusions	The patients with persisted minimal residual disease or cytogenetic relapse after allo-HSCT will be include in this group.

Primary Outcome Measures

Name	Time	Method
Relapse - free survival	24 months	Estimate time to morphological relapse by Kaplan Mayer

Secondary Outcome Measures

Name	Time	Method
Relapse rate analysis	24 months	Cumulative incidence of patients with relapse by Gray's test
Incidence of acute GVHD grade II-IV	125 days	Cumulative incidence of patients with acute GVHD II-IV grade by Gray's test
Graft - versus -host-disease free/relapse free survival	24 months	Estimate time to date of III-IV acute GVHD (aGVHD), chronic GVHD (cGVHD) requiring systemic immunosuppressive treatment, disease relapse or death from any other cause by Kaplan Mayer
Incidence of moderate and severe chronic GVHD	24 months	Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria by Gray's test
Relapse - free survival	24 months	Estimate time to appearing of MRD or morphological relapse by Kaplan Mayer
Non-relapse mortality analysis	24 months	Cumulative incidence of patients with mortality without hematological relapse of malignancy
Overall survival analysis	24 months	Estimate time to death by Kaplan Mayer
Incidence of achievement MRD negative status	24 months	Cumulative incidence of patients with MRD positive status, who had responds to therapy Gray's test

Trial Locations

Locations (1)

RM Gorbacheva Research Institute; 🇷🇺 Saint Petersburg, Russian Federation