Chemoradiotherapy With Targeted Immunotherapy in Pediatric Lymphoma

NCT ID: NCT05253495

Last Updated: 2025-06-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-01
• Study Completion Date: 2028-06-30

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.

Conditions

Non-hodgkin Lymphoma; Hodgkin Lymphoma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1a

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).

Group Type: EXPERIMENTAL

DOC Group B

Intervention Type: DRUG

Cyclophosphamide 300 mg x1; dexamethasone x 7; vincristine x1

Pv-COMRAD 1 and 2 Group B

Intervention Type: DRUG

polatuzumab vedotin x1; dexamethasone x 5; vincristine x1, cyclophosphamide x 3; doxorubicin x1; methotrexate x; rituximab 2x; ITT x1

Pv-R-CYM 1 and 2 Group B

Intervention Type: DRUG

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

Cohort 1b

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.

Group Type: EXPERIMENTAL

DOC Group C

Intervention Type: DRUG

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

MAD CPR 1 and 2

Intervention Type: DRUG

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

Pv-R CYVE 1 and 2

Intervention Type: DRUG

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

Pv-R CYVE-MTX 1 and 2

Intervention Type: DRUG

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)

MAD CP

Intervention Type: DRUG

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

Pv-Cytarabine/etoposide

Intervention Type: DRUG

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

AD CP

Intervention Type: DRUG

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

Involved Site Radiation Therapy

Intervention Type: RADIATION

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.

Cohort 2a

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.

Group Type: EXPERIMENTAL

Bv-AVD-R 1 and 2: COHORT IIa

Intervention Type: DRUG

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

Bv-NVD-R, Cycle 1-2

Intervention Type: DRUG

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

Bv-NVD-R, Cycle 1-4 SER

Intervention Type: DRUG

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

Cohort 2b

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.

Group Type: EXPERIMENTAL

Bv-AVD-R

Intervention Type: DRUG

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

Bv-NVD-R, Cycle 1-4 RER

Intervention Type: DRUG

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

Bv-NAVD-R, Cycle 1-2

Intervention Type: DRUG

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

Involved Site Radiation Therapy

Intervention Type: RADIATION

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.

Interventions

DOC Group B

Cyclophosphamide 300 mg x1; dexamethasone x 7; vincristine x1

Intervention Type: 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

Intervention Type: DRUG

Pv-R-CYM 1 and 2 Group B

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

Intervention Type: DRUG

DOC Group C

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

Intervention Type: 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

Intervention Type: DRUG

Pv-R CYVE 1 and 2

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

Intervention Type: 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)

Intervention Type: DRUG

MAD CP

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

Intervention Type: DRUG

Pv-Cytarabine/etoposide

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

Intervention Type: DRUG

AD CP

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

Intervention Type: DRUG

Bv-AVD-R 1 and 2: COHORT IIa

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

Intervention Type: DRUG

Bv-NVD-R, Cycle 1-2

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

Intervention Type: DRUG

Bv-NVD-R, Cycle 1-4 SER

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

Intervention Type: DRUG

Bv-AVD-R

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

Intervention Type: DRUG

Bv-NVD-R, Cycle 1-4 RER

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

Intervention Type: DRUG

Bv-NAVD-R, Cycle 1-2

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

Intervention Type: DRUG

Involved 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.

Intervention Type: RADIATION

Other Intervention Names

Reduction Phase; Induction 1 and 2; Consolidation 1 and 2; Reduction with IT; Induction 1 and 2 Group C; Consolidation 1 and 2 Group C CNS Negative; Consolidation 1 and 2 Group C CNS Positive; Maintenance 1 Group C; Maintenance 2, 4 Group C; Maintenance 3 Group C; Intermediate Risk cohort IIa; Cohort IIa Rapid Early Responders; Cohort IIa Slow Early Responders; High-Risk cohort IIb; cohort IIb Rapid Early Responders; cohort IIb Slow Early Responders; Cohort II ONLY

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)

• Minimum Eligible Age: 3 Years
• Maximum Eligible Age: 39 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

New York Medical College

OTHER

Sponsor Role: lead

Responsible Party

Mitchell Cairo

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mitchell Cairo, MD

Role: PRINCIPAL_INVESTIGATOR

New York Medical Center

Locations

University of Alabama

Birmingham, Alabama, United States

Site Status: NOT_YET_RECRUITING

University of Flordia

Gainsville, Florida, United States

Site Status: RECRUITING

New York Medical College

Vallhala, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Mitchell Cairo, MD

Role: CONTACT

mitchell_cairo@nymc.edu

9145942150

Lauren Harrison, RN

Role: CONTACT

lauren_harrison@nymc.edu

617-285-7844

Facility Contacts

Ana Xavier, MD

Role: primary

axavier@peds.uab.edu

William Slayton, MD

Role: primary

slaytwb@peds.ufl.edu

Mitchell S Cairo, MD

Role: primary

mitchell_cairo@nymc.edu

914-594-2150

Other Identifiers

14601

Identifier Type: -

Identifier Source: org_study_id