B-cell Mature Non-Hodgkin's Lymphoma Treatment Protocol in Children and Adolescents 2021

Официальное название

B-cell Mature Non-Hodgkin's Lymphoma Treatment Protocol in Children and Adolescents 2021 (B-NHL-M-2021)

Обзор

The aim of the trial is to evaluate the molecular characteristics and MDD/MRD of B-NHL in pediatric patients in order to identify on the one hand the very high risk group and to prescribe them more intensive treatment on the other hand to identify those patients who don't need very aggressive therapy. One more study question is to evaluate the role of PET/CT in assessment of the completeness of remission. The following primary study questions are going to be analyzed: * the effectiveness (event-free survival) in pediatric patients with very limited mature B-NHL (R1 - stage I and II R) of substituting anthracyclines and vincristine by the rituximab without compromising survival rates. * the effectiveness (event-free survival) in pediatric patients with limited mature B-NHL (R2 - stage I and II NR) of substituting anthracyclines by the rituximab without compromising survival rates. * the effectiveness (event-free survival) in pediatric patients with advanced VHR mature B-NHL (R4 - stages with unfavourable genetics of substituting standard chemotherapy by "second-line" block VICI in order to improve results Secondary study questions will address * additional parameters for immune reconstitution, lymphocyte subpopulations, immunoglobulin levels, vaccination titers and infection rates * kinetics of immune reconstitution after treatment

Подробное описание

Detailed Description:

Risk group stratification:

R1: resection status: complete, stage I and II R2: resection status: incomplete, stage I and II R3: resection status: incomplete, stage III and LDH \< 2 x ULN R4: resection status: incomplete, stage III and LDH ≥ 2 x ULN, stage IV/B-AL and CNS negative; CNS +

For patients with very limited disease (R1- stage I/II СR), the addition of rituximab might allow the omission of anthracyclines and vincristine without jeopardizing survival rates but reducing acute and long term toxicities. In this treatment arm, it is tested whether the event-free survival is similar to that of the historical control For patients with limited disease (R2- stage I/II NR), the addition of rituximab might allow the omission of anthracyclines without jeopardizing survival rates but reducing acute and long term toxicities.

For patients with limited disease (R3 - stage III and LDH \< 2 x ULN ), the addition of rituximab might allow reduce the number of blocks to four without jeopardizing survival rates but reducing toxicities For patients with obligate factors of poor prognosis (additional adverse cytogenetic findings (TP-53, 11qLOH) it is tested whether the event-free survival can be improved by adding rituximab and adding blocks R-VICI

Вмешательства

• Препарат Cyclophosphamide, Cytarabine, Dexamethasone, Etoposide, Ifosfamide, Methotrexate
  For patients with very limited disease (R1- stage I/II СR), the addition of rituximab might allow the omission of anthracyclines and vincristine without jeopardizing survival rates but reducing acute and long term toxicities. In this treatment arm, it is tested whether the event-free survival is similar to that of the historical control
• Препарат Cyclophosphamide, Cytarabine, Dexamethasone, Etoposide, Ifosfamide, Methotrexate, Vincristine
  R2: Drug: Rituximab 2 doses of Rituximab (375 mg/m²) before the start of the first chemotherapy cycle, 2 doses of Rituximab before the start of the second chemotherapy cycle
• Препарат Cyclophosphamide, Cytarabine, Dexamethasone, Doxorubicin hydrochloride, Etoposide, Ifosfamide, Methotrexate, vincristine
  2 doses of Rituximab (375 mg/m²) before the start of the first chemotherapy cycle, 2 doses of Rituximab before the start of the second
• Препарат Cyclophosphamide , Cytarabine, Dexamethasone, Doxorubicin hydrochloride, Etoposide, Ifosfamide, Methotrexate, Vincristine, Сarboplatine, CCNU/ BCNU, Melphalan, Idarubicin
  Rituximab 4 doses of Rituximab (375 mg/m²) before the start of the first chemotherapy cycle, Further

Первичные конечные точки

• Event-free survival [Срок оценки: 3 years after the start of therapy]
• Event-free survival [Срок оценки: 7 years after the start of therapy]

Вторичные конечные точки (12)

• assessment of MDD and MRD indicators, p53 and 11qLOH status in patients on the B-NHL-M-2021 protocol [Срок оценки: 3 years after the start of therapy]
• assessment of MDD and MRD indicators, p53 and 11qLOH status in patients on the B-NHL-M-2021 protocol [Срок оценки: 7 years after the start of therapy]
• assessment of PET-CT results - initial and control points (early PET response).after the 2nd block [Срок оценки: after the 2nd block - CT with CL of the involved areas, PET-CT examination on the 14th day (maximum on the 17th day) after the last injection of CT, IPT, MRD in the bone marrow - after 4th block - CT with the CL of the involved areas]
• assessment of PET-CT results - initial and control points (early PET response) after 4th block [Срок оценки: PET-CT examination on the 14th day (maximum on the 17th day) after the last administration of CT, MRD in the bone marrow if present after the 2nd block]
• Relapse-free survival (RFS) [Срок оценки: 3 years after the start of therapy]
• Relapse-free survival (RFS) [Срок оценки: 7 years after the start of therapy]
• Response rate (RR) [ and after second course and after two injections of rituximab]. Complete response, partial remission, stable disease or progressive disease [Срок оценки: 3 years after the start of therapy]
• Response rate (RR) [ and after second course and after two injections of rituximab]. Complete response, partial remission, stable disease or progressive disease [Срок оценки: 7 years after the start of therapy]
• Rate of patients achieving normal immunoglobulin level [Срок оценки: 12 months after start of treatment]
• Rate of patients with normal lymphocyte subpopulations in the peripheral blood 12 months after start of treatment [Срок оценки: 12 months after start of treatment]
• Interval to normal lymphocyte subpopulations in the peripheral blood. [Срок оценки: 7 years after the start of therapy]
• Rate of patients with sufficient titers after vaccination one year after start of treatment [Срок оценки: 1 year after start of treatment]

Критерии участия

Критерии включения

• Age at diagnosis 0 to 18 years.
• The diagnosis of Burkitt's lymphoma, Diffuse large B-cell lymphom, primary mediastinal lymphoma, primary CNS lymphoma, B-cell (Burkitt) AL
• Informed consent of the patient parents (guardians) to be treated

Критерии исключения

• previous malignancy, prior organ transplant, HIV infection or AIDS or severe immunodeficiency
• hypersensitivity to rituximab or to ingredients of other IMPs.
• no informed consent of the patient parents (guardians) to be treated

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Россия · 1 центр

• Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Imm — Moscow

Идентификаторы

NCT: NCT05518383 · NCHPOI-2021-07

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗