Clinical trial

Reducing the Burden of Oncologic Chemoradiotherapy And Radiation Exposure From Diagnostic Imaging by Utilizing Targeted Immunotherapy in Children, Adolescents and Young Adults With Lymphoma

Name

14601

Description

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).

Trial arms

Trial start

2022-02-01

Estimated PCD

2027-12-31

Trial end

2028-06-30

Status

Recruiting

Phase

Early phase I

Treatment

DOC Group B

Cyclophosphamide 300 mg x1; dexamethasone x 7; vincristine x1

Arms:

Cohort 1a

Other names:

Reduction Phase

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

Arms:

Cohort 1a

Other names:

Induction 1 and 2

Pv-R-CYM 1 and 2 Group B

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

Arms:

Cohort 1a

Other names:

Consolidation 1 and 2

DOC Group C

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

Arms:

Cohort 1b

Other names:

Reduction with IT

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

Arms:

Cohort 1b

Other names:

Induction 1 and 2 Group C

Pv-R CYVE 1 and 2

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

Arms:

Cohort 1b

Other names:

Consolidation 1 and 2 Group C CNS Negative

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)

Arms:

Cohort 1b

Other names:

Consolidation 1 and 2 Group C CNS Positive

MAD CP

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

Arms:

Cohort 1b

Other names:

Maintenance 1 Group C

Pv-Cytarabine/etoposide

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

Arms:

Cohort 1b

Other names:

Maintenance 2, 4 Group C

AD CP

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

Arms:

Cohort 1b

Other names:

Maintenance 3 Group C

Bv-AVD-R 1 and 2: COHORT IIa

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

Arms:

Cohort 2a

Other names:

Intermediate Risk cohort IIa

Bv-NVD-R, Cycle 1-2

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

Arms:

Cohort 2a

Other names:

Cohort IIa Rapid Early Responders

Bv-NVD-R, Cycle 1-4 SER

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

Arms:

Cohort 2a

Other names:

Cohort IIa Slow Early Responders

Bv-AVD-R

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

Arms:

Cohort 2b

Other names:

High-Risk cohort IIb

Bv-NVD-R, Cycle 1-4 RER

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

Arms:

Cohort 2b

Other names:

cohort IIb Rapid Early Responders

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;

Arms:

Cohort 2b

Other names:

cohort IIb Slow Early Responders

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.

Arms:

Cohort 1b, Cohort 2b

Other names:

Cohort II ONLY

Size

Primary endpoint

Grade 3 and 4 Adverse Events related to polatuzumab vedotin

1 year

Grade 3 and 4 Adverse events related to nivolumab

1 year

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)

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 80, 'type': 'ESTIMATED'}}

Updated at

2023-10-26

1 organization

13 products

2 indications

Organization

New York Medical College

Product

DOC Group B

Indication

Non-Hodgkin Lymphoma

Indication