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Completed

NCT Number: NCT05009719

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

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.

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Key information

Age range

4 month–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

RM Gorbacheva Research Institute

Saint Petersburg, 197022, Russia

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

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.

Primary outcomes

  1. Relapse - free survival

    Time frame: 24 months

    Estimate time to morphological relapse by Kaplan Mayer

Secondary outcomes

  1. Overall survival analysis

    Time frame: 24 months

    Estimate time to death by Kaplan Mayer

  2. Relapse rate analysis

    Time frame: 24 months

    Cumulative incidence of patients with relapse by Gray's test

  3. Non-relapse mortality analysis

    Time frame: 24 months

    Cumulative incidence of patients with mortality without hematological relapse of malignancy

  4. Incidence of acute GVHD grade II-IV

    Time frame: 125 days

    Cumulative incidence of patients with acute GVHD II-IV grade by Gray's test

  5. Incidence of moderate and severe chronic GVHD

    Time frame: 24 months

    Cumulative incidence of patients with moderate and severe chronic GVHD according to NIH 2015 criteria by Gray's test

  6. Incidence of achievement MRD negative status

    Time frame: 24 months

    Cumulative incidence of patients with MRD positive status, who had responds to therapy Gray's test

  7. Relapse - free survival

    Time frame: 24 months

    Estimate time to appearing of MRD or morphological relapse by Kaplan Mayer

  8. Graft - versus -host-disease free/relapse free survival

    Time frame: 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

Sponsors and collaborators

Lead sponsor

St. Petersburg State Pavlov Medical University

Other

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2023
Study completion
2024
First posted
Aug 17, 2021
Registry last updated
Jun 25, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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