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

NCT ID: NCT05009719

Last Updated: 2024-06-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-01
• Study Completion Date: 2024-04-01

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

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Prophylactic

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.

Group Type: EXPERIMENTAL

Prophylactic Donor lymphocytes infusions

Intervention Type: 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.

Preventive

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

Group Type: EXPERIMENTAL

Preventive Donor lymphocytes infusions

Intervention Type: 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.

Interventions

Prophylactic Donor lymphocytes infusions

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.

Intervention Type: BIOLOGICAL

Preventive Donor lymphocytes infusions

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 4 Months
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Petersburg State Pavlov Medical University

OTHER

Sponsor Role: lead

Responsible Party

Ivan S Moiseev

Vice-director for science RM Gorbacheva Institute

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

RM Gorbacheva Research Institute

Saint Petersburg, , Russia

Countries

Russia

Other Identifiers

hsct/dli

Identifier Type: -

Identifier Source: org_study_id