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

NCT ID: NCT05518383

Last Updated: 2022-08-26

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-25
• Study Completion Date: 2027-05-16

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

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

R1: stage I and II

R1: resection status: complete, stage I and II

Group Type: EXPERIMENTAL

Cyclophosphamide, Cytarabine, Dexamethasone, Etoposide, Ifosfamide, Methotrexate

Intervention Type: DRUG

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

R2: incomplete, stage I and II

R2: resection status: incomplete, stage I and II

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

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

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

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

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

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

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

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

Group Type: EXPERIMENTAL

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

Intervention Type: DRUG

Rituximab 4 doses of Rituximab (375 mg/m²) before the start of the first chemotherapy cycle, Further

Interventions

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 1 Day
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Dmitry Rogachev National Medical Research Center Of Pediatric Hematology, Oncology and Immunology

Moscow, RF, Russia

Site Status: RECRUITING

Countries

Russia

Central Contacts

Yulia Abugova

Role: CONTACT

Yuliya.Abugova@fccho-moscow.ru

+7-916-074-74-76

Facility Contacts

Yulia Abugova

Role: primary

Other Identifiers

NCHPOI-2021-07

Identifier Type: -

Identifier Source: org_study_id