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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Prophylactic | Experimental | 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. |
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| Preventive | Experimental | The patients with persisted minimal residual disease or cytogenetic relapse after allo-HSCT will be include in this group. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Relapse - free survival | Estimate time to morphological relapse by Kaplan Mayer | 24 months |
| Measure | Description | Time Frame |
|---|---|---|
| Overall survival analysis | Estimate time to death by Kaplan Mayer | 24 months |
| Relapse rate analysis | Cumulative incidence of patients with relapse by Gray's test |
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Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| RM Gorbacheva Research Institute | Saint Petersburg | 197022 | Russia |
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| ID | Term |
|---|---|
| D019337 | Hematologic Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D006402 | Hematologic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
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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.
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| 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. |
|
| 24 months |
| Non-relapse mortality analysis | Cumulative incidence of patients with mortality without hematological relapse of malignancy | 24 months |
| Incidence of acute GVHD grade II-IV | Cumulative incidence of patients with acute GVHD II-IV grade by Gray's test | 125 days |
| 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 |
| Incidence of achievement MRD negative status | Cumulative incidence of patients with MRD positive status, who had responds to therapy Gray's test | 24 months |
| Relapse - free survival | Estimate time to appearing of MRD or morphological relapse by Kaplan Mayer | 24 months |
| 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 |