Clinical trial NCT05009719: Risk-adapted Donor Lymphocyte Infusion After Allo-HSCT in Children With Hematologic Malignancy
Official title: Study of the Efficacy and Safety of Risk-adapted Donor Lymphocyte Infusions for the Prophylaxis and Prevention of Relapses After Allogeneic Hematopoietic Stem Cell Transplantation in Children and Adolescent With Hematologic Malignancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Hematologic Malignancy
Keywords: allo-HSCT
children
Donor LymphocyteI Infusion
Lead sponsor: St. Petersburg State Pavlov Medical University
Sponsor class: OTHER
First posted: 2021-08-17
Enrollment: 50
Sex: ALL
Minimum age (years): 4
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: PREVENTION

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.


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

Primary outcomes:
measure: Relapse - free survival
timeFrame: 24 months
Secondary outcomes:
measure: Overall survival analysis
timeFrame: 24 months
measure: Relapse rate analysis
timeFrame: 24 months
measure: Non-relapse mortality analysis
timeFrame: 24 months
measure: Incidence of acute GVHD grade II-IV
timeFrame: 125 days
measure: Incidence of moderate and severe chronic GVHD
timeFrame: 24 months
measure: Incidence of achievement MRD negative status
timeFrame: 24 months
measure: Relapse - free survival
timeFrame: 24 months
measure: Graft - versus -host-disease free/relapse free survival
timeFrame: 24 months
Other outcomes:
Locations:
city: Saint Petersburg
country: Russian Federation
facility: RM Gorbacheva Research Institute
Study officials:
References: