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

St. Petersburg State Pavlov Medical University

Status and phase: Completed; Phase 2; Phase 1

Conditions: Hematologic Malignancy

Treatments: Biological: Prophylactic Donor lymphocytes infusions; Biological: Preventive Donor lymphocytes infusions

Study type: Interventional

Funder types: Other

Identifiers

NCT05009719

hsct/dli

Details and patient eligibility

About

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.

Enrollment: 50 patients

Sex: All

Ages: 4 months to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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50 participants in 2 patient groups

Prophylactic

Experimental group

Description:

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.

Treatment:

Biological: Prophylactic Donor lymphocytes infusions

Preventive

Experimental group

Description:

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

Treatment:

Biological: Preventive Donor lymphocytes infusions