Clinical trial NCT05518383: B-cell Mature Non-Hodgkin's Lymphoma Treatment Protocol in Children and Adolescents 2021
Official title: B-cell Mature Non-Hodgkin's Lymphoma Treatment Protocol in Children and Adolescents 2021 (B-NHL-M-2021)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Non-hodgkin Lymphoma,B Cell
Burkitt Lymphoma
Primary Mediastinal Lymphoma
Primary CNS Lymphoma
Diffuse Large B-cell Lymphoma
Keywords: B-cell mature non-Hodgkin's lymphoma
Burkitt's lymphoma
Diffuse large B-cell lymphoma
primary mediastinal lymphoma, primary CNS lymphoma
rituximab
children, adolescents
treatment
Lead sponsor: Federal Research Institute of Pediatric Hematology, Oncology and Immunology
Sponsor class: OTHER
First posted: 2022-08-26
Enrollment: 300
Sex: ALL
Minimum age (years): 1
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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

Detailed description: 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

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Event-free survival
timeFrame: 3 years after the start of therapy
measure: Event-free survival
timeFrame: 7 years after the start of therapy
Secondary outcomes:
measure: assessment of MDD and MRD indicators, p53 and 11qLOH status in patients on the B-NHL-M-2021 protocol
timeFrame: 3 years after the start of therapy
measure: assessment of MDD and MRD indicators, p53 and 11qLOH status in patients on the B-NHL-M-2021 protocol
timeFrame: 7 years after the start of therapy
measure: assessment of PET-CT results - initial and control points (early PET response).after the 2nd block
timeFrame: 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
measure: assessment of PET-CT results - initial and control points (early PET response) after 4th block
timeFrame: 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
measure: Relapse-free survival (RFS)
timeFrame: 3 years after the start of therapy
measure: Relapse-free survival (RFS)
timeFrame: 7 years after the start of therapy
measure: Response rate (RR) [ and after second course and after two injections of rituximab]. Complete response, partial remission, stable disease or progressive disease
timeFrame: 3 years after the start of therapy
measure: Response rate (RR) [ and after second course and after two injections of rituximab]. Complete response, partial remission, stable disease or progressive disease
timeFrame: 7 years after the start of therapy
measure: Rate of patients achieving normal immunoglobulin level
timeFrame: 12 months after start of treatment
measure: Rate of patients with normal lymphocyte subpopulations in the peripheral blood 12 months after start of treatment
timeFrame: 12 months after start of treatment
measure: Interval to normal lymphocyte subpopulations in the peripheral blood.
timeFrame: 7 years after the start of therapy
measure: Rate of patients with sufficient titers after vaccination one year after start of treatment
timeFrame: 1 year after start of treatment
measure: Immune reconstitution rate (only in R1/R2 patients)
timeFrame: 1 year after start of treatment
measure: Time interval from start of treatment to normal CD19 positive B-cells in the peripheral blood.
timeFrame: 1 year after start of treatment
Other outcomes:
Locations:
city: Moscow
country: Russian Federation
facility: Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology
state: RF
Study officials:
References: