Chemoradiotherapy With Targeted Immunotherapy in Pediatric Lymphoma

NCT05253495 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 14601
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 3

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).

Conditions

Non-hodgkin Lymphoma; Hodgkin Lymphoma

Outcome Measures

Primary Outcomes (2)

• Grade 3 and 4 Adverse Events related to polatuzumab vedotin

  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

  1 year

• Grade 3 and 4 Adverse events related to nivolumab

  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

  1 year

Study Arms (4)

Cohort 1a

EXPERIMENTAL

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).

Drug: DOC Group B; Drug: Pv-COMRAD 1 and 2 Group B; Drug: Pv-R-CYM 1 and 2 Group B

Cohort 1b

EXPERIMENTAL

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.

Drug: DOC Group C; Drug: MAD CPR 1 and 2; Drug: Pv-R CYVE 1 and 2; Drug: Pv-R CYVE-MTX 1 and 2; Drug: MAD CP; Drug: Pv-Cytarabine/etoposide; Drug: AD CP; Radiation: Involved Site Radiation Therapy

Cohort 2a

EXPERIMENTAL

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.

Drug: Bv-AVD-R 1 and 2: COHORT IIa; Drug: Bv-NVD-R, Cycle 1-2; Drug: Bv-NVD-R, Cycle 1-4 SER

Cohort 2b

EXPERIMENTAL

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.

Drug: Bv-AVD-R; Drug: Bv-NVD-R, Cycle 1-4 RER; Drug: Bv-NAVD-R, Cycle 1-2; Radiation: Involved Site Radiation Therapy

Interventions

DOC Group B DRUG

Cyclophosphamide 300 mg x1; dexamethasone x 7; vincristine x1

Also known as: Reduction Phase

Cohort 1a

Pv-COMRAD 1 and 2 Group B DRUG

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

Also known as: Induction 1 and 2

Cohort 1a

Pv-R-CYM 1 and 2 Group B DRUG

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

Also known as: Consolidation 1 and 2

Cohort 1a

DOC Group C DRUG

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

Also known as: Reduction with IT

Cohort 1b

MAD CPR 1 and 2 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

Also known as: Induction 1 and 2 Group C

Cohort 1b

Pv-R CYVE 1 and 2 DRUG

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

Also known as: Consolidation 1 and 2 Group C CNS Negative

Cohort 1b

Pv-R CYVE-MTX 1 and 2 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)

Also known as: Consolidation 1 and 2 Group C CNS Positive

Cohort 1b

MAD CP DRUG

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

Also known as: Maintenance 1 Group C

Cohort 1b

Pv-Cytarabine/etoposide DRUG

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

Also known as: Maintenance 2, 4 Group C

Cohort 1b

AD CP DRUG

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

Also known as: Maintenance 3 Group C

Cohort 1b

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

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

Also known as: Intermediate Risk cohort IIa

Cohort 2a

Bv-NVD-R, Cycle 1-2 DRUG

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

Also known as: Cohort IIa Rapid Early Responders

Cohort 2a

Bv-NVD-R, Cycle 1-4 SER DRUG

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

Also known as: Cohort IIa Slow Early Responders

Cohort 2a

Bv-AVD-R DRUG

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

Also known as: High-Risk cohort IIb

Cohort 2b

Bv-NVD-R, Cycle 1-4 RER DRUG

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

Also known as: cohort IIb Rapid Early Responders

Cohort 2b

Bv-NAVD-R, Cycle 1-2 DRUG

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

Also known as: cohort IIb Slow Early Responders

Cohort 2b

Involved Site Radiation Therapy 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.

Also known as: Cohort II ONLY

Cohort 1b; Cohort 2b

Eligibility Criteria

• Age: 3 Years - 39 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• New York Medical College: lead

Study Sites (3)

University of Alabama

Birmingham, Alabama, 35233, United States

NOT YET RECRUITING

University of Flordia

Gainsville, Florida, 32610, United States

RECRUITING

New York Medical College

Vallhala, New York, 10595, United States

RECRUITING

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin; Hodgkin Disease

Interventions

Etoposide

Condition Hierarchy (Ancestors)

Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Mitchell Cairo, MD

  New York Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mitchell Cairo, MD

CONTACT

9145942150; mitchell_cairo@nymc.edu

Lauren Harrison, RN

CONTACT

617-285-7844; lauren_harrison@nymc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 14, 2022
• First Posted: February 23, 2022
• Study Start: February 1, 2022
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: June 13, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)