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

Primary Purpose

Hematologic Malignancy

Status

Recruiting

Phase

Phase 1

Locations

Russian Federation

Study Type

Interventional

Intervention

Prophylactic Donor lymphocytes infusions

Preventive Donor lymphocytes infusions

About this trial

This is an interventional prevention trial for Hematologic Malignancy focused on measuring allo-HSCT, children, Donor LymphocyteI Infusion

Eligibility Criteria

4 Months - 18 Years (Child, Adult)All SexesDoes not accept 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

Sites / Locations

RM Gorbacheva Research InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Prophylactic

Preventive

Arm 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.

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

Outcomes

Primary Outcome Measures

Relapse - free survival

Estimate time to morphological relapse by Kaplan Mayer

Secondary Outcome Measures

Overall survival analysis

Estimate time to death by Kaplan Mayer

Relapse rate analysis

Cumulative incidence of patients with relapse by Gray's test

Non-relapse mortality analysis

Cumulative incidence of patients with mortality without hematological relapse of malignancy

Incidence of acute GVHD grade II-IV

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

Incidence of moderate and severe chronic GVHD

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

Incidence of achievement MRD negative status

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

Relapse - free survival

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

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

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

Full Information

NCT ID

NCT05009719

First Posted

August 16, 2021

Last Updated

October 27, 2022

Sponsor

St. Petersburg State Pavlov Medical University

1. Study Identification

Unique Protocol Identification Number

NCT05009719

Brief Title

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

2. Study Status

Record Verification Date

October 2022

Overall Recruitment Status

Recruiting

Study Start Date

April 1, 2021 (Actual)

Primary Completion Date

April 1, 2023 (Anticipated)

Study Completion Date

April 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

St. Petersburg State Pavlov Medical University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Hematologic Malignancy

Keywords

allo-HSCT, children, Donor LymphocyteI Infusion

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

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.

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Prophylactic

Arm Type

Experimental

Arm 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.

Arm Title

Preventive

Arm Type

Experimental

Arm Description

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

Intervention Type

Biological

Intervention Name(s)

Prophylactic Donor lymphocytes infusions

Intervention Description

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

Intervention Name(s)

Preventive Donor lymphocytes infusions

Intervention Description

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 Outcome Measure Information:

Title

Relapse - free survival

Description

Estimate time to morphological relapse by Kaplan Mayer

Time Frame

24 months

Secondary Outcome Measure Information:

Title

Overall survival analysis

Description

Estimate time to death by Kaplan Mayer

Time Frame

24 months

Title

Relapse rate analysis

Description

Cumulative incidence of patients with relapse by Gray's test

Time Frame

24 months

Title

Non-relapse mortality analysis

Description

Cumulative incidence of patients with mortality without hematological relapse of malignancy

Time Frame

24 months

Title

Incidence of acute GVHD grade II-IV

Description

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

Time Frame

125 days

Title

Incidence of moderate and severe chronic GVHD

Description

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

Time Frame

24 months

Title

Incidence of achievement MRD negative status

Description

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

Time Frame

24 months

Title

Relapse - free survival

Description

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

Time Frame

24 months

Title

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

Description

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

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

4 Months

Maximum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Liudmila S Zubarovskaya, MD, Prof.

Phone

89219731431

zubarovskaya_ls@mail.ru

First Name & Middle Initial & Last Name or Official Title & Degree

Liubov A Tsvetkova, MD

Phone

89216433905

tsvetluibov@mail.ru

Facility Information:

Facility Name

RM Gorbacheva Research Institute

City

Saint Petersburg

ZIP/Postal Code

197022

Country

Russian Federation

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Liudmila Zubarovskaya, MD, Prof.

Phone

89219731431

zubarovskaya_ls@mail.ru

First Name & Middle Initial & Last Name & Degree

Liubov Tsvetkova, MD

Phone

89216433905

tsvetluibov@mail.ru

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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