RADICAL: Chemoradiotherapy With Targeted Immunotherapy in Pediatric Lymphoma

Sponsor
New York Medical College (Other)
Overall Status
Recruiting
CT.gov ID
NCT05253495
Collaborator
(none)
80
Enrollment
1
Location
4
Arms
76.9
Anticipated Duration (Months)
1
Patients Per Site Per Month

Study Details

Study Description

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 DiseaseIntervention/TreatmentPhase
  • Drug: DOC Group B
  • Drug: COMRAD 1 and 2 Group B
  • Drug: 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

Study Design

Study Type:
Interventional
Anticipated 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 :
Feb 1, 2022
Anticipated Primary Completion Date :
Dec 31, 2027
Anticipated Study Completion Date :
Jun 30, 2028

Arms and Interventions

ArmIntervention/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 cyclophosphamide, vincristine, methotrexate, rituximab, doxorubicin (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 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 Names:
  • Reduction Phase
  • Drug: COMRAD 1 and 2 Group B
    dexamethasone x 5; vincristine x1, cyclophosphamide x 3; doxorubicin x1; methotrexate x; rituximab 2x; ITT x1
    Other Names:
  • Induction 1 and 2
  • Drug: R-CYM 1 and 2 Group B
    methotrexate x 1; rituximab x 1; cytarabine x 5;
    Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Maintenance 1 Group C
  • Drug: Pv-Cytarabine/etoposide
    polatuzumab vedotin x 1; cytarabine x 5; etoposide x 3;
    Other Names:
  • Maintenance 2, 4 Group C
  • Drug: AD CP
    polatuzumab vedotin x 1; cyclophosphamide x2; doxorubicin x 2;
    Other Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • 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 Names:
  • Cohort II ONLY
  • Outcome Measures

    Primary Outcome Measures

    1. 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

    2. 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

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    3 Years to 39 Years
    Sexes Eligible for Study:
    All
    Accepts 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)

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1New York Medical CollegeValhallaNew YorkUnited States10595

    Sponsors and Collaborators

    • New York Medical College

    Investigators

    • Principal Investigator: Mitchell Cairo, MD, New York Medical Center

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Mitchell Cairo, Principal Investigator, New York Medical College
    ClinicalTrials.gov Identifier:
    NCT05253495
    Other Study ID Numbers:
    • 14601
    First Posted:
    Feb 23, 2022
    Last Update Posted:
    Mar 10, 2022
    Last Verified:
    Feb 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 10, 2022