Chemoradiotherapy With Targeted Immunotherapy in Pediatric Lymphoma (RADICAL)

New York Medical College

Status and phase: Enrolling; Phase 2

Conditions: Hodgkin Lymphoma; Non-hodgkin Lymphoma

Treatments: Drug: Bv-AVD-R 1 and 2: COHORT IIa; Drug: AD CP; Drug: Pv-R CYVE-MTX 1 and 2; Drug: Bv-NVD-R, Cycle 1-2; Radiation: Involved Site Radiation Therapy; Drug: Pv-Cytarabine/etoposide; Drug: Bv-NAVD-R, Cycle 1-2; Drug: Pv-R-CYM 1 and 2 Group B; Drug: Bv-AVD-R; Drug: Bv-NVD-R, Cycle 1-4 RER; Drug: DOC Group B; Drug: MAD CP; Drug: Pv-R CYVE 1 and 2; Drug: MAD CPR 1 and 2; Drug: Pv-COMRAD 1 and 2 Group B; Drug: Bv-NVD-R, Cycle 1-4 SER; Drug: DOC Group C

Study type: Interventional

Funder types: Other

Identifiers

NCT05253495

14601

Details and patient eligibility

About

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).

Full 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.

Enrollment: 80 estimated patients

Sex: All

Ages: 3 to 39 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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80 participants in 4 patient groups

Cohort 1a

Experimental group

Description:

Mature B-cell Non-hodgkin Lymphoma \[MB NHL\], GROUP B will receive reduction therapy with dexamethasone, vincristine and cyclophosphamide (DOC), then undergo disease assessment. If tumor reduction ≥ 20%, will get induction 1 and 2 with polatuzumab vedotin, cyclophosphamide, vincristine, methotrexate, rituximab, doxorubicin (Pv-COM3RA25D) 1 and 2, then Consolidation 1 with rituximab, cytarabine, methotrexate (R-CYM) . Patients will undergo disease assessment post Consolidation 1. If no residual disease, they proceed to receive Consolidation 2 with Pv-R-CYM (R-CYM 2). Cohort Ia patients with \< 20% tumor reduction post DOC will be assigned to Cohort Ib starting at Induction 1. Cohort Ia patients with residual disease post Consolidation 1 will be assigned to Cohort Ib starting at Consolidation 1 polatuzumab vedotin, rituximab, high dose cytarabine, cytarabine, high dose methotrexate, etoposide (Pv-R-CYVE 1).

Treatment:

Drug: Pv-COMRAD 1 and 2 Group B

Drug: DOC Group B

Drug: Pv-R-CYM 1 and 2 Group B

Cohort 1b

Experimental group

Description:

MB NHL, GROUP C will receive reduction therapy with DOC. Patients with \< 20% tumor reduction will be off protocol. Patients with ≥ 20% tumor reduction get Induction 1 and 2 with cyclophosphamide, doxorubicin, dexamethasone, high dose methotrexate, polatuzumab vedotin, and triple intrathecal chemotherapy (M8A30D CPR) 1 and 2, then Consolidation 1 with Pv-R-CYVE 1. If no residual disease, they get Consolidation 2 (Pv-R-CYVE 2), followed by Maintenance (M) 1 with M8A30D CP, M 2 with Pv-cytarabine/etoposide, M 3 with cyclophosphamide, doxorubicin, dexamethasone and polatuzumab vedotin (A30D CP), and M 4 with Pv-cytarabine/etoposide. Cohort Ib patients with CNS disease will receive additional intrathecal chemotherapy and high dose methotrexate during Consolidation.

Treatment:

Drug: DOC Group C

Drug: MAD CPR 1 and 2

Drug: MAD CP

Drug: Pv-R CYVE 1 and 2

Drug: Pv-Cytarabine/etoposide

Radiation: Involved Site Radiation Therapy

Drug: AD CP

Drug: Pv-R CYVE-MTX 1 and 2

Cohort 2a

Experimental group

Description:

Classical Hodgkin lymphoma, INTERMEDIATE RISK will receive 2 cycles of brentuximab vedotin (Bv), doxorubicin, vinblastine, dactinomycin, and rituximab (Bv-AVD-R 1 and 2). Response assessment with FDG-PET scan after 2 cycles of Bv-AVD-R. Rapid early responders (RER) will continue therapy with 2 cycles of Bv, vinblastine, dactinomycin, nivolumab, and rituximab (Bv-NVD-R 1 and 2). RERs will not receive radiation therapy. Patients deemed to be Slow Early Responders (SER) after 2 cycles of Bv-AVD-R will continue therapy with 4 cycles of Bv-NVD-R (Bv-NVD-R 1, 2, 3, and 4). Radiation therapy will be given at completion of therapy only for SER patients NOT achieving complete remission at the end of chemoimmunotherapy.

Treatment:

Drug: Bv-NVD-R, Cycle 1-4 SER

Drug: Bv-NVD-R, Cycle 1-2

Drug: Bv-AVD-R 1 and 2: COHORT IIa

Cohort 2b

Experimental group

Description:

COHORT IIb (Classical Hodgkin lymphoma, HIGH RISK) Cohort IIb patients will receive 2 cycles of brentuximab vedotin (Bv), doxorubicin, vinblastine, dactinomycin, and rituximab (Bv-AVD-R 1 and 2). Response assessment will be performed with FDG-PET scan after 2 cycles of Bv-AVD-R. Rapid early responders (RER) will continue therapy with 4 cycles of Bv, vinblastine, dactinomycin, nivolumab, and rituximab (Bv-NVD-R 1, 2, 3, and 4). RERs will not receive radiation therapy. Patients deemed to be Slow Early Responders (SER) after 2 cycles of Bv-AVD-R will receive 2 cycles of Bv, nivolumab, doxorubicin, vinblastine, dactinomycin, and rituximab (Bv-NAVD-R 1 and 2), followed by 4 cycles of Bv, vinblastine, dactinomycin, nivolumab, and rituximab (Bv-NVD-R 1, 2, 3, and 4). Radiation therapy will be given at completion of therapy only for SER patients NOT achieving complete remission at the end of chemoimmunotherapy.

Treatment:

Drug: Bv-NVD-R, Cycle 1-4 RER

Drug: Bv-AVD-R

Drug: Bv-NAVD-R, Cycle 1-2

Radiation: Involved Site Radiation Therapy