Chemoradiotherapy With Targeted Immunotherapy in Pediatric Lymphoma

Official title

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

Overview

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).

Detailed description

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.

Interventions

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

Primary outcome measures

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

Eligibility criteria

Inclusion criteria

• 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

Exclusion criteria

• 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)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 3 centers

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

Identifiers

NCT: NCT05253495 · 14601

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗