Hodgkin Lymphoma, Non-hodgkin Lymphoma
Conditions
Brief 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.
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.
Sponsors
New York Medical College
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
3 Years to 39 Years
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Grade 3 and 4 Adverse Events related to polatuzumab vedotin | 1 year | to evaluate the DLTs of polatuzumab vedotin (Pv) in combination with rituximab (RTX) containing French-American-British (FAB) chemoimmunotherapy, with reduced dose anthracycline to MB-NHL |
| Grade 3 and 4 Adverse events related to nivolumab | 1 year | To evaluate the DLTs of nivolumab to the backbone of reduced toxicity chemoimmunotherapy with brentuximab vedotin (Bv), vinblastine, dacarbazine and rituximab, with reduced dose anthracycline in intermediate and high risk cHL |
Countries
United States
Contacts
Primary ContactMitchell Cairo, MD
Backup ContactLauren Harrison, RN
Outcome results
None listed