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

August 25, 2022 updated by: Federal Research Institute of Pediatric Hematology, Oncology and Immunology

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

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

Study Overview

Status

Recruiting

Conditions

Intervention / 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

Study Type

Interventional

Enrollment (Anticipated)

300

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Russian Federation
    • RF
      • Moscow, RF, Russian Federation, 117198
        • Recruiting
        • Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology
        • Contact:
          • Yulia Abugova

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 day to 18 years (ADULT, CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: R1: stage I and II
R1: resection status: complete, stage I and II
Drug: 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
EXPERIMENTAL: R2: incomplete, stage I and II
R2: resection status: incomplete, stage I and II
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
EXPERIMENTAL: R3: incomplete, stage III and LDH < 2 x ULN
R3: resection status: incomplete, stage III and LDH < 2 x ULN
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
EXPERIMENTAL: 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 +
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Event-free survival
Time Frame: 3 years after the start of therapy
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
Time Frame: 7 years after the start of therapy
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of patients with normal lymphocyte subpopulations in the peripheral blood 12 months after start of treatment
Time Frame: 12 months after start of treatment
12 months after start of treatment
Rate of patients with sufficient titers after vaccination one year after start of treatment
Time Frame: 1 year after start of treatment
1 year after start of treatment
assessment of MDD and MRD indicators, p53 and 11qLOH status in patients on the B-NHL-M-2021 protocol
Time Frame: 3 years after the start of therapy
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
Time Frame: 7 years after the start of therapy
7 years after the start of therapy
assessment of PET-CT results - initial and control points (early PET response).after the 2nd block
Time Frame: 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
measurement of tumor volume at diagnosis and measurement of tumor volume reduction after therapy in percent 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 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
Time Frame: 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
measurement of tumor volume at diagnosis and measurement of tumor volume reduction after therapy in percent after 4th block - CT with the CL of the involved areas , 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 After the 6th block - CT with CL of the involved areas
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)
Time Frame: 3 years after the start of therapy
RFS is defined as time from start of treatment up to event or to date of last contact for patients without event. The following occurrences are defined as an event: non-response, progressive disease, or relapse.
3 years after the start of therapy
Relapse-free survival (RFS)
Time Frame: 7 years after the start of therapy
RFS is defined as time from start of treatment up to event or to date of last contact for patients without event. The following occurrences are defined as an event: non-response, progressive disease, or relapse.
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
Time Frame: 3 years after the start of therapy
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
Time Frame: 7 years after the start of therapy
7 years after the start of therapy
Rate of patients achieving normal immunoglobulin level
Time Frame: 12 months after start of treatment
12 months after start of treatment
Interval to normal lymphocyte subpopulations in the peripheral blood.
Time Frame: 7 years after the start of therapy
7 years after the start of therapy
Immune reconstitution rate (only in R1/R2 patients)
Time Frame: 1 year after start of treatment
1 year after start of treatment
Time interval from start of treatment to normal CD19 positive B-cells in the peripheral blood.
Time Frame: 1 year after start of treatment
1 year after start of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Federal Research Institute of Pediatric Hematology, Oncology and Immunology

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

May 25, 2022

Primary Completion (ANTICIPATED)

May 16, 2025

Study Completion (ANTICIPATED)

May 16, 2027

Study Registration Dates

First Submitted

August 23, 2022

First Submitted That Met QC Criteria

August 25, 2022

First Posted (ACTUAL)

August 26, 2022

Study Record Updates

Last Update Posted (ACTUAL)

August 26, 2022

Last Update Submitted That Met QC Criteria

August 25, 2022

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NCHPOI-2021-07

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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