Chemoradiotherapy With Targeted Immunotherapy in Pediatric Lymphoma

Официальное название

Reducing the Burden of Oncologic Chemoradiotherapy And Radiation Exposure From Diagnostic Imaging by Utilizing Targeted Immunotherapy in Children, Adolescents and Young Adults With Lymphoma

Обзор

The addition of targeted immunotherapy will be safe and well tolerated and facilitate the reduction of anthracycline exposure while preserving lymphoma disease control in children, adolescents and young adults (CAYA) with mature B-cell non-Hodgkin lymphoma (MB-NHL) and classical Hodgkin lymphoma (cHL).

Подробное описание

The primary objective is 1) to determine feasibility and safety, as defined by dose limiting toxicities (DLTs), of adding polatuzumab vedotin (Pv) in combination with rituximab (RTX) containing French-American-British (FAB) chemoimmunotherapy, with reduced dose anthracycline, in CAYA with intermediate and high risk newly diagnosed MB-NHL; 2) To define the feasibility and safety, as defined by DLTs, of the addition of nivolumab to the backbone of reduced toxicity chemoimmunotherapy with brentuximab vedotin (Bv), vinblastine, dacarbazine and rituximab, with reduced dose anthracycline, in CAYA with newly diagnosed intermediate and high risk cHL.

Вмешательства

• Препарат DOC Group B
  Cyclophosphamide 300 mg x1; dexamethasone x 7; vincristine x1
• Препарат Pv-COMRAD 1 and 2 Group B
  polatuzumab vedotin x1; dexamethasone x 5; vincristine x1, cyclophosphamide x 3; doxorubicin x1; methotrexate x; rituximab 2x; ITT x1
• Препарат Pv-R-CYM 1 and 2 Group B
  polatuzumab vedotin x 1; methotrexate x 1; rituximab x 1; cytarabine x 5;
• Препарат DOC Group C
  cyclophosphamide x 1, dexamethasone x 5; vincristine x1; IT triples x 3
• Препарат MAD CPR 1 and 2
  methotrexate x 1; dexamethasone x 5; polatuzumab Vedotin x 1, cyclophosphamide x 3; doxorubicin x 1; rituximab x2; IT triples x 2 in induction 1, IT triples x 2 in induction 2
• Препарат Pv-R CYVE 1 and 2
  Polatuzumab Vedotin x 1; Rituximab x 1; Cytarabine x 5; Etoposide x4;
• Препарат Pv-R CYVE-MTX 1 and 2
  Polatuzumab Vedotin x 1; Rituximab x 1; Cytarabine x 5; Etoposide x4; high dose cytarabine x4; high dose methotrexate x 1 (only consolidation 1); IT triples x 2 (only 1 in consolidation 2)
• Препарат MAD CP
  dexamethasone x1; polatuzumab vedotin x 1; cyclophosphamide x 2; doxorubicin x 1; high dose methotrexate x 1; IT triples x 1
• Препарат Pv-Cytarabine/etoposide
  polatuzumab vedotin x 1; cytarabine x 5; etoposide x 3;
• Препарат AD CP
  polatuzumab vedotin x 1; cyclophosphamide x2; doxorubicin x 2;

Первичные конечные точки

• Grade 3 and 4 Adverse Events related to polatuzumab vedotin [Срок оценки: 1 year]
• Grade 3 and 4 Adverse events related to nivolumab [Срок оценки: 1 year]

Критерии участия

Критерии включения

• Newly diagnosed patients with histologically or cytologically proven newly diagnosed MB-NHL or cHL according to WHO Classification who meet the following criteria are eligible:

COHORT I:

Burkitt lymphoma (ICD-O 9687/3) Burkitt-like lymphoma with 11q aberration (ICD-O 9687/3) Diffuse large B-cell lymphoma, NOS (ICD-O 9680/3) High grade B-cell lymphoma (ICD-O 9680/3)

COHORT Ia: stage III with LDH ≥ 2 ULN OR stage IV (5-24% bone marrow lymphoma infiltration) (GROUP B)61

COHORT Ib: any CNS involvement and/or BM involvement (≥ 25% lymphoma cells) (GROUP C)61 OR patients with less than 20% tumor size reduction post chemotherapy with cyclophosphamide, dexamethasone, vincristine (DOC Reduction for Cohort Ia).

COHORT II Classical Hodgkin lymphoma (ICD-O 9650/3, 9663/3, 9651/3, 9652/3, 9653/3)

COHORT IIa: stage I-IIA with bulky ± E, I-IIB no bulky ± E, IIIA ± E (INTERMEDIATE RISK)

COHORT IIb: stage IIB with bulky ± E, IIIA with bulky ± E, IIIB, IV (HIGH RISK)

• Adequate organ function

Критерии исключения

• Primary mediastinal B-cell lymphoma (PMBL)
• T-cell/histiocyte-rich large B-cell lymphoma
• Gray zone lymphoma
• Follicular lymphoma
• Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL)
• Posttransplant lymphoproliferative lymphoma (PTLD)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 3 центра

• University of Alabama — Birmingham
• University of Flordia — Gainsville
• New York Medical College — Vallhala

Идентификаторы

NCT: NCT05253495 · 14601

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗