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

Hematologic Malignancy Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05009719
• Other study ID #: hsct/dli
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: April 1, 2021
• Est. completion date: April 1, 2024

Study information

• Verified date: January 2024
• Source: St. Petersburg State Pavlov Medical University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 50
• Est. completion date: April 1, 2024
• Est. primary completion date: April 1, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 4 Months to 18 Years

Eligibility

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

Related Conditions & MeSH terms

• Hematologic Malignancy
• Hematologic Neoplasms
• Neoplasms

Intervention

Biological:
• 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.
• 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.

Locations

Country	Name	City	State
Russian Federation	RM Gorbacheva Research Institute	Saint Petersburg

Sponsors (1)

Lead Sponsor	Collaborator
St. Petersburg State Pavlov Medical University

Country where clinical trial is conducted

Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relapse - free survival	Estimate time to morphological relapse by Kaplan Mayer	24 months
Secondary	Overall survival analysis	Estimate time to death by Kaplan Mayer	24 months
Secondary	Relapse rate analysis	Cumulative incidence of patients with relapse by Gray's test	24 months
Secondary	Non-relapse mortality analysis	Cumulative incidence of patients with mortality without hematological relapse of malignancy	24 months
Secondary	Incidence of acute GVHD grade II-IV	Cumulative incidence of patients with acute GVHD II-IV grade by Gray's test	125 days
Secondary	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	24 months
Secondary	Incidence of achievement MRD negative status	Cumulative incidence of patients with MRD positive status, who had responds to therapy Gray's test	24 months
Secondary	Relapse - free survival	Estimate time to appearing of MRD or morphological relapse by Kaplan Mayer	24 months
Secondary	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	24 months