Chemoradiotherapy With Targeted Immunotherapy in Pediatric Lymphoma

Hodgkin Lymphoma Clinical Trial

— 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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05253495
• Other study ID #: 14601
• Status: Recruiting
• Phase: Phase 2
• Start date: February 1, 2022
• Est. completion date: June 30, 2028

Study information

• Verified date: October 2023
• Source: New York Medical College
• Contact: Mitchell Cairo, MD
• Phone: 9145942150
• Email: mitchell_cairo[@]nymc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 80
• Est. completion date: June 30, 2028
• Est. primary completion date: December 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Years to 39 Years

Eligibility

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)

Related Conditions & MeSH terms

• Hodgkin Lymphoma
• Lymphoma
• Non-hodgkin Lymphoma

Intervention

Drug:
• DOC Group B
Cyclophosphamide 300 mg x1; dexamethasone x 7; vincristine x1
• 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
• Pv-R-CYM 1 and 2 Group B
polatuzumab vedotin x 1; methotrexate x 1; rituximab x 1; cytarabine x 5;
• DOC Group C
cyclophosphamide x 1, dexamethasone x 5; vincristine x1; IT triples x 3
• 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
• Pv-R CYVE 1 and 2
Polatuzumab Vedotin x 1; Rituximab x 1; Cytarabine x 5; Etoposide x4;
• 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)
• MAD CP
dexamethasone x1; polatuzumab vedotin x 1; cyclophosphamide x 2; doxorubicin x 1; high dose methotrexate x 1; IT triples x 1
• Pv-Cytarabine/etoposide
polatuzumab vedotin x 1; cytarabine x 5; etoposide x 3;
• AD CP
polatuzumab vedotin x 1; cyclophosphamide x2; doxorubicin x 2;
• Bv-AVD-R 1 and 2: COHORT IIa
brentuximab vedotin x 2; doxorubicin x 2; vinblastine x 2; dacarbazine 2x; rituximab x 2
• Bv-NVD-R, Cycle 1-2
brentuximab vedotin x 2; nivolumab x 2; vinblastine x2; dacarbazine x 2; rituximab x 2;
• Bv-NVD-R, Cycle 1-4 SER
brentuximab vedotin x 2; nivolumab x 2; vinblastine x 2; rituximab x 2;
• Bv-AVD-R
Brentuximab vedotin x2; doxorubicin x2; vinblastine x 2; dacarbazine x 2; rituximab x2;
• Bv-NVD-R, Cycle 1-4 RER
brentuximab vedotin x 2; nivolumab x 2; vinblastine x 2; dacarbazine x 2; rituximab x 2;
• 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;

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.

Locations

Country	Name	City	State
United States	University of Alabama	Birmingham	Alabama
United States	University of Flordia	Gainesville	Florida
United States	New York Medical College	Valhalla	New York

Sponsors (1)

Lead Sponsor	Collaborator
New York Medical College

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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