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

Summary

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.

Arms & interventions

• DrugDOC Group B

  Cyclophosphamide 300 mg x1; dexamethasone x 7; vincristine x1

• DrugPv-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

• DrugPv-R-CYM 1 and 2 Group B

  polatuzumab vedotin x 1; methotrexate x 1; rituximab x 1; cytarabine x 5;

• DrugDOC Group C

  cyclophosphamide x 1, dexamethasone x 5; vincristine x1; IT triples x 3

• DrugMAD 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

• DrugPv-R CYVE 1 and 2

  Polatuzumab Vedotin x 1; Rituximab x 1; Cytarabine x 5; Etoposide x4;

• DrugPv-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)

• DrugMAD CP

  dexamethasone x1; polatuzumab vedotin x 1; cyclophosphamide x 2; doxorubicin x 1; high dose methotrexate x 1; IT triples x 1

• DrugPv-Cytarabine/etoposide

  polatuzumab vedotin x 1; cytarabine x 5; etoposide x 3;

• DrugAD CP

  polatuzumab vedotin x 1; cyclophosphamide x2; doxorubicin x 2;

• DrugBv-AVD-R 1 and 2: COHORT IIa

  brentuximab vedotin x 2; doxorubicin x 2; vinblastine x 2; dacarbazine 2x; rituximab x 2

• DrugBv-NVD-R, Cycle 1-2

  brentuximab vedotin x 2; nivolumab x 2; vinblastine x2; dacarbazine x 2; rituximab x 2;

• DrugBv-NVD-R, Cycle 1-4 SER

  brentuximab vedotin x 2; nivolumab x 2; vinblastine x 2; rituximab x 2;

• DrugBv-AVD-R

  Brentuximab vedotin x2; doxorubicin x2; vinblastine x 2; dacarbazine x 2; rituximab x2;

• DrugBv-NVD-R, Cycle 1-4 RER

  brentuximab vedotin x 2; nivolumab x 2; vinblastine x 2; dacarbazine x 2; rituximab x 2;

• DrugBv-NAVD-R, Cycle 1-2

  brentuximab vedotin x 2; nivolumab x 2; doxorubicin x 2; vinblastine x 2; dacarbazine x 2; rituximab x 2;

• RadiationInvolved Site Radiation Therapy

  21 Gy in 14 fractions of 1.50 Gy per day. The treatment will be given 5 days per week. All fields shall be treated once each day. The total elapsed treatment time will be 2.8 weeks (14 sessions) for each field.

Outcome measures

Eligibility criteria