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Chemoradiotherapy With Targeted Immunotherapy in Pediatric Lymphoma (RADICAL)

Primary Purpose

Non-hodgkin Lymphoma, Hodgkin Lymphoma

Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
DOC Group B
Pv-COMRAD 1 and 2 Group B
Pv-R-CYM 1 and 2 Group B
DOC Group C
MAD CPR 1 and 2
Pv-R CYVE 1 and 2
Pv-R CYVE-MTX 1 and 2
MAD CP
Pv-Cytarabine/etoposide
AD CP
Bv-AVD-R 1 and 2: COHORT IIa
Bv-NVD-R, Cycle 1-2
Bv-NVD-R, Cycle 1-4 SER
Bv-AVD-R
Bv-NVD-R, Cycle 1-4 RER
Bv-NAVD-R, Cycle 1-2
Involved Site Radiation Therapy
Sponsored by
New York Medical College
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-hodgkin Lymphoma

Eligibility Criteria

3 Years - 39 Years (Child, Adult)All SexesDoes not accept 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)

Sites / Locations

  • New York Medical CollegeRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Cohort 1a

Cohort 1b

Cohort 2a

Cohort 2b

Arm 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).

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.

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.

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.

Outcomes

Primary Outcome Measures

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
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

Secondary Outcome Measures

Full Information

First Posted
February 14, 2022
Last Updated
June 9, 2022
Sponsor
New York Medical College
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1. Study Identification

Unique Protocol Identification Number
NCT05253495
Brief Title
Chemoradiotherapy With Targeted Immunotherapy in Pediatric Lymphoma
Acronym
RADICAL
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2022
Overall Recruitment Status
Recruiting
Study Start Date
February 1, 2022 (Actual)
Primary Completion Date
December 31, 2027 (Anticipated)
Study Completion Date
June 30, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
New York Medical College

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-hodgkin Lymphoma, Hodgkin Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
80 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1a
Arm Type
Experimental
Arm 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).
Arm Title
Cohort 1b
Arm Type
Experimental
Arm 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.
Arm Title
Cohort 2a
Arm Type
Experimental
Arm 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.
Arm Title
Cohort 2b
Arm Type
Experimental
Arm 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.
Intervention Type
Drug
Intervention Name(s)
DOC Group B
Other Intervention Name(s)
Reduction Phase
Intervention Description
Cyclophosphamide 300 mg x1; dexamethasone x 7; vincristine x1
Intervention Type
Drug
Intervention Name(s)
Pv-COMRAD 1 and 2 Group B
Other Intervention Name(s)
Induction 1 and 2
Intervention Description
polatuzumab vedotin x1; dexamethasone x 5; vincristine x1, cyclophosphamide x 3; doxorubicin x1; methotrexate x; rituximab 2x; ITT x1
Intervention Type
Drug
Intervention Name(s)
Pv-R-CYM 1 and 2 Group B
Other Intervention Name(s)
Consolidation 1 and 2
Intervention Description
polatuzumab vedotin x 1; methotrexate x 1; rituximab x 1; cytarabine x 5;
Intervention Type
Drug
Intervention Name(s)
DOC Group C
Other Intervention Name(s)
Reduction with IT
Intervention Description
cyclophosphamide x 1, dexamethasone x 5; vincristine x1; IT triples x 3
Intervention Type
Drug
Intervention Name(s)
MAD CPR 1 and 2
Other Intervention Name(s)
Induction 1 and 2 Group C
Intervention Description
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
Intervention Name(s)
Pv-R CYVE 1 and 2
Other Intervention Name(s)
Consolidation 1 and 2 Group C CNS Negative
Intervention Description
Polatuzumab Vedotin x 1; Rituximab x 1; Cytarabine x 5; Etoposide x4;
Intervention Type
Drug
Intervention Name(s)
Pv-R CYVE-MTX 1 and 2
Other Intervention Name(s)
Consolidation 1 and 2 Group C CNS Positive
Intervention Description
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
Intervention Name(s)
MAD CP
Other Intervention Name(s)
Maintenance 1 Group C
Intervention Description
dexamethasone x1; polatuzumab vedotin x 1; cyclophosphamide x 2; doxorubicin x 1; high dose methotrexate x 1; IT triples x 1
Intervention Type
Drug
Intervention Name(s)
Pv-Cytarabine/etoposide
Other Intervention Name(s)
Maintenance 2, 4 Group C
Intervention Description
polatuzumab vedotin x 1; cytarabine x 5; etoposide x 3;
Intervention Type
Drug
Intervention Name(s)
AD CP
Other Intervention Name(s)
Maintenance 3 Group C
Intervention Description
polatuzumab vedotin x 1; cyclophosphamide x2; doxorubicin x 2;
Intervention Type
Drug
Intervention Name(s)
Bv-AVD-R 1 and 2: COHORT IIa
Other Intervention Name(s)
Intermediate Risk cohort IIa
Intervention Description
brentuximab vedotin x 2; doxorubicin x 2; vinblastine x 2; dacarbazine 2x; rituximab x 2
Intervention Type
Drug
Intervention Name(s)
Bv-NVD-R, Cycle 1-2
Other Intervention Name(s)
Cohort IIa Rapid Early Responders
Intervention Description
brentuximab vedotin x 2; nivolumab x 2; vinblastine x2; dacarbazine x 2; rituximab x 2;
Intervention Type
Drug
Intervention Name(s)
Bv-NVD-R, Cycle 1-4 SER
Other Intervention Name(s)
Cohort IIa Slow Early Responders
Intervention Description
brentuximab vedotin x 2; nivolumab x 2; vinblastine x 2; rituximab x 2;
Intervention Type
Drug
Intervention Name(s)
Bv-AVD-R
Other Intervention Name(s)
High-Risk cohort IIb
Intervention Description
Brentuximab vedotin x2; doxorubicin x2; vinblastine x 2; dacarbazine x 2; rituximab x2;
Intervention Type
Drug
Intervention Name(s)
Bv-NVD-R, Cycle 1-4 RER
Other Intervention Name(s)
cohort IIb Rapid Early Responders
Intervention Description
brentuximab vedotin x 2; nivolumab x 2; vinblastine x 2; dacarbazine x 2; rituximab x 2;
Intervention Type
Drug
Intervention Name(s)
Bv-NAVD-R, Cycle 1-2
Other Intervention Name(s)
cohort IIb Slow Early Responders
Intervention Description
brentuximab vedotin x 2; nivolumab x 2; doxorubicin x 2; vinblastine x 2; dacarbazine x 2; rituximab x 2;
Intervention Type
Radiation
Intervention Name(s)
Involved Site Radiation Therapy
Other Intervention Name(s)
Cohort II ONLY
Intervention Description
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.
Primary Outcome Measure Information:
Title
Grade 3 and 4 Adverse Events related to polatuzumab vedotin
Description
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
Time Frame
1 year
Title
Grade 3 and 4 Adverse events related to nivolumab
Description
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
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
3 Years
Maximum Age & Unit of Time
39 Years
Accepts Healthy Volunteers
No
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mitchell Cairo, MD
Phone
9145942150
Email
mitchell_cairo@nymc.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Lauren Harrison, RN
Phone
617-285-7844
Email
lauren_harrison@nymc.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mitchell Cairo, MD
Organizational Affiliation
New York Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
ZIP/Postal Code
10595
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mitchell S Cairo, MD
Phone
914-594-2150
Email
mitchell_cairo@nymc.edu
First Name & Middle Initial & Last Name & Degree
Mitchell S. Cairo, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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Chemoradiotherapy With Targeted Immunotherapy in Pediatric Lymphoma

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