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

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Status and phase: Enrolling; Phase 4

Conditions: Primary CNS Lymphoma; Primary Mediastinal Lymphoma; Diffuse Large B-cell Lymphoma; Burkitt Lymphoma; Non-hodgkin Lymphoma,B Cell

Treatments: Drug: Cyclophosphamide , Cytarabine, Dexamethasone, Doxorubicin hydrochloride, Etoposide, Ifosfamide, Methotrexate, Vincristine, Сarboplatine, CCNU/ BCNU, Melphalan, Idarubicin; Drug: Cyclophosphamide, Cytarabine, Dexamethasone, Etoposide, Ifosfamide, Methotrexate, Vincristine; Drug: Cyclophosphamide, Cytarabine, Dexamethasone, Doxorubicin hydrochloride, Etoposide, Ifosfamide, Methotrexate, vincristine; Drug: Cyclophosphamide, Cytarabine, Dexamethasone, Etoposide, Ifosfamide, Methotrexate

Study type: Interventional

Funder types: Other

Identifiers

NCT05518383

NCHPOI-2021-07

Details and patient eligibility

About

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

Full 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

Enrollment: 300 estimated patients

Sex: All

Ages: 1 day to 18 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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300 participants in 4 patient groups

R1: stage I and II

Experimental group

Description:

R1: resection status: complete, stage I and II

Treatment:

Drug: Cyclophosphamide, Cytarabine, Dexamethasone, Etoposide, Ifosfamide, Methotrexate

R2: incomplete, stage I and II

Experimental group

Description:

R2: resection status: incomplete, stage I and II

Treatment:

Drug: Cyclophosphamide, Cytarabine, Dexamethasone, Etoposide, Ifosfamide, Methotrexate, Vincristine

R3: incomplete, stage III and LDH < 2 x ULN

Experimental group

Description:

R3: resection status: incomplete, stage III and LDH \< 2 x ULN

Treatment:

Drug: Cyclophosphamide, Cytarabine, Dexamethasone, Doxorubicin hydrochloride, Etoposide, Ifosfamide, Methotrexate, vincristine

R4: stage III and LDH ≥ 2 x ULN, stage IV/B-AL and CNS negative; CNS +

Experimental group

Description:

R4: resection status: incomplete, stage III and LDH ≥ 2 x ULN, stage IV/B-AL and CNS negative; CNS +

Treatment:

Drug: Cyclophosphamide , Cytarabine, Dexamethasone, Doxorubicin hydrochloride, Etoposide, Ifosfamide, Methotrexate, Vincristine, Сarboplatine, CCNU/ BCNU, Melphalan, Idarubicin