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

NCT05518383 | Recruiting Phase 4

• 1 other identifier: NCHPOI-2021-07
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

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

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

Outcome Measures

Primary Outcomes (2)

• Event-free survival

  Event-free survival The following occurrences are defined as an event: non-response, progressive disease or relapse, treatment related death, death of any other cause or diagnosis of secondary malignancies.

  3 years after the start of therapy

• Event-free survival

  Event-free survival The following occurrences are defined as an event: non-response, progressive disease or relapse, treatment related death, death of any other cause or diagnosis of secondary malignancies.

  7 years after the start of therapy

Secondary Outcomes (14)

• assessment of MDD and MRD indicators, p53 and 11qLOH status in patients on the B-NHL-M-2021 protocol

  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

  7 years after the start of therapy

• assessment of PET-CT results - initial and control points (early PET response).after the 2nd block

  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

  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)

  3 years after the start of therapy

Study Arms (4)

R1: stage I and II

EXPERIMENTAL

R1: resection status: complete, stage I and II

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

R2: incomplete, stage I and II

EXPERIMENTAL

R2: resection status: incomplete, stage I and II

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

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

EXPERIMENTAL

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

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

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

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

Interventions

Cyclophosphamide, Cytarabine, Dexamethasone, Etoposide, Ifosfamide, Methotrexate 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

R1: stage I and II

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

R2: incomplete, stage I and II

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

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

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

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

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

Eligibility Criteria

• Age: 1 Day - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Federal Research Institute of Pediatric Hematology, Oncology and Immunology: lead

Study Sites (1)

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

Moscow, RF, 117198, Russia

RECRUITING

MeSH Terms

Conditions

Burkitt Lymphoma; Lymphoma, Large B-Cell, Diffuse

Interventions

Cyclophosphamide; Cytarabine; Dexamethasone; Etoposide; Ifosfamide; Methotrexate; Vincristine; Doxorubicin; Lomustine; Carmustine; Melphalan; Idarubicin

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Glucosides; Glycosides; Carbohydrates; Oxazines; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Indolizidines; Indolizines; Daunorubicin; Anthracyclines; Naphthacenes; Aminoglycosides; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins

Central Study Contacts

Yulia Abugova

CONTACT

+7-916-074-74-76; Yuliya.Abugova@fccho-moscow.ru

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 23, 2022
• First Posted: August 26, 2022
• Study Start: May 25, 2022
• Primary Completion: May 16, 2025
• Study Completion (Estimated): May 16, 2027
• Last Updated: August 26, 2022

Record last verified: 2022-05

Locations

RU (1)