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Chemoradiotherapy With Targeted Immunotherapy in Pediatric Lymphoma (RADICAL)

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ClinicalTrials.gov Identifier: NCT05253495
Recruitment Status : Recruiting
First Posted : February 23, 2022
Last Update Posted : June 13, 2022
Sponsor:
Information provided by (Responsible Party):
Mitchell Cairo, New York Medical College

Study Description
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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).

Condition or disease Intervention/treatment Phase
Non-hodgkin Lymphoma Hodgkin Lymphoma Drug: DOC Group B Drug: Pv-COMRAD 1 and 2 Group B Drug: Pv-R-CYM 1 and 2 Group B 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 Drug: Bv-AVD-R 1 and 2: COHORT IIa Drug: Bv-NVD-R, Cycle 1-2 Drug: Bv-NVD-R, Cycle 1-4 SER Drug: Bv-AVD-R Drug: Bv-NVD-R, Cycle 1-4 RER Drug: Bv-NAVD-R, Cycle 1-2 Radiation: Involved Site Radiation Therapy Phase 2

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Reducing the Burden of Oncologic Chemoradiotherapy And Radiation Exposure From Diagnostic Imaging by Utilizing Targeted Immunotherapy in Children, Adolescents and Young Adults With Lymphoma
Actual Study Start Date : February 1, 2022
Estimated Primary Completion Date : December 31, 2027
Estimated Study Completion Date : June 30, 2028

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: 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).

 Drug: DOC Group B
Cyclophosphamide 300 mg x1; dexamethasone x 7; vincristine x1
Other Name: Reduction Phase

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
Other Name: Induction 1 and 2

Drug: Pv-R-CYM 1 and 2 Group B
polatuzumab vedotin x 1; methotrexate x 1; rituximab x 1; cytarabine x 5;
Other Name: Consolidation 1 and 2
Experimental: 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.
 Drug: DOC Group C
cyclophosphamide x 1, dexamethasone x 5; vincristine x1; IT triples x 3
Other Name: Reduction with IT

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
Other Name: Induction 1 and 2 Group C

Drug: Pv-R CYVE 1 and 2
Polatuzumab Vedotin x 1; Rituximab x 1; Cytarabine x 5; Etoposide x4;
Other Name: Consolidation 1 and 2 Group C CNS Negative

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)
Other Name: Consolidation 1 and 2 Group C CNS Positive

Drug: MAD CP
dexamethasone x1; polatuzumab vedotin x 1; cyclophosphamide x 2; doxorubicin x 1; high dose methotrexate x 1; IT triples x 1
Other Name: Maintenance 1 Group C

Drug: Pv-Cytarabine/etoposide
polatuzumab vedotin x 1; cytarabine x 5; etoposide x 3;
Other Name: Maintenance 2, 4 Group C

Drug: AD CP
polatuzumab vedotin x 1; cyclophosphamide x2; doxorubicin x 2;
Other Name: Maintenance 3 Group C

Radiation: 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.
Other Name: Cohort II ONLY
Experimental: 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.
 Drug: Bv-AVD-R 1 and 2: COHORT IIa
brentuximab vedotin x 2; doxorubicin x 2; vinblastine x 2; dacarbazine 2x; rituximab x 2
Other Name: Intermediate Risk cohort IIa

Drug: Bv-NVD-R, Cycle 1-2
brentuximab vedotin x 2; nivolumab x 2; vinblastine x2; dacarbazine x 2; rituximab x 2;
Other Name: Cohort IIa Rapid Early Responders

Drug: Bv-NVD-R, Cycle 1-4 SER
brentuximab vedotin x 2; nivolumab x 2; vinblastine x 2; rituximab x 2;
Other Name: Cohort IIa Slow Early Responders
Experimental: 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.
 Drug: Bv-AVD-R
Brentuximab vedotin x2; doxorubicin x2; vinblastine x 2; dacarbazine x 2; rituximab x2;
Other Name: High-Risk cohort IIb

Drug: Bv-NVD-R, Cycle 1-4 RER
brentuximab vedotin x 2; nivolumab x 2; vinblastine x 2; dacarbazine x 2; rituximab x 2;
Other Name: cohort IIb Rapid Early Responders

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;
Other Name: cohort IIb Slow Early Responders

Radiation: 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.
Other Name: Cohort II ONLY


Outcome Measures
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Primary Outcome Measures :
  1. Grade 3 and 4 Adverse Events related to polatuzumab vedotin [ Time Frame: 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

  2. Grade 3 and 4 Adverse events related to nivolumab [ Time Frame: 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


Eligibility Criteria
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Ages Eligible for Study:   3 Years to 39 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05253495


Contacts
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Contact: Mitchell Cairo, MD 9145942150 mitchell_cairo@nymc.edu
Contact: Lauren Harrison, RN 617-285-7844 lauren_harrison@nymc.edu

Locations
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United States, New York
New York Medical College Recruiting
Valhalla, New York, United States, 10595
Contact: Mitchell S Cairo, MD    914-594-2150    mitchell_cairo@nymc.edu   
Principal Investigator: Mitchell S. Cairo, MD         
Sponsors and Collaborators
New York Medical College
Investigators
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Principal Investigator: Mitchell Cairo, MD New York Medical Center
More Information
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Responsible Party: Mitchell Cairo, Principal Investigator, New York Medical College
ClinicalTrials.gov Identifier: NCT05253495    
Other Study ID Numbers: 14601
First Posted: February 23, 2022    Key Record Dates
Last Update Posted: June 13, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Lymphoma
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cytarabine
Etoposide
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
 Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs