Ignite Creation Date:
2025-12-24 @ 1:39 PM
Ignite Modification Date:
2026-01-01 @ 11:19 AM
Study NCT ID:
NCT05253495
Status:
RECRUITING
Last Update Posted:
2025-06-13
First Post:
2022-02-14
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Chemoradiotherapy With Targeted Immunotherapy in Pediatric Lymphoma
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D008228', 'term': 'Lymphoma, Non-Hodgkin'}, {'id': 'D006689', 'term': 'Hodgkin Disease'}], 'ancestors': [{'id': 'D008223', 'term': 'Lymphoma'}, {'id': 'D009370', 'term': 'Neoplasms by Histologic Type'}, {'id': 'D009369', 'term': 'Neoplasms'}, {'id': 'D008232', 'term': 'Lymphoproliferative Disorders'}, {'id': 'D008206', 'term': 'Lymphatic Diseases'}, {'id': 'D006425', 'term': 'Hemic and Lymphatic Diseases'}, {'id': 'D007160', 'term': 'Immunoproliferative Disorders'}, {'id': 'D007154', 'term': 'Immune System Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D005047', 'term': 'Etoposide'}], 'ancestors': [{'id': 'D011034', 'term': 'Podophyllotoxin'}, {'id': 'D013764', 'term': 'Tetrahydronaphthalenes'}, {'id': 'D009281', 'term': 'Naphthalenes'}, {'id': 'D011084', 'term': 'Polycyclic Aromatic Hydrocarbons'}, {'id': 'D006841', 'term': 'Hydrocarbons, Aromatic'}, {'id': 'D006844', 'term': 'Hydrocarbons, Cyclic'}, {'id': 'D006838', 'term': 'Hydrocarbons'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D011083', 'term': 'Polycyclic Compounds'}, {'id': 'D005960', 'term': 'Glucosides'}, {'id': 'D006027', 'term': 'Glycosides'}, {'id': 'D002241', 'term': 'Carbohydrates'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NON_RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ESTIMATED', 'count': 80}}, 'statusModule': {'overallStatus': 'RECRUITING', 'startDateStruct': {'date': '2022-02-01', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-06', 'completionDateStruct': {'date': '2028-06-30', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-06-10', 'studyFirstSubmitDate': '2022-02-14', 'studyFirstSubmitQcDate': '2022-02-22', 'lastUpdatePostDateStruct': {'date': '2025-06-13', 'type': 'ACTUAL'}, 'studyFirstPostDateStruct': {'date': '2022-02-23', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2027-12-31', 'type': 'ESTIMATED'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Grade 3 and 4 Adverse Events related to polatuzumab vedotin', 'timeFrame': '1 year', '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'}, {'measure': 'Grade 3 and 4 Adverse events related to nivolumab', 'timeFrame': '1 year', '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'}]}, 'oversightModule': {'isUsExport': False, 'oversightHasDmc': True, 'isFdaRegulatedDrug': True, 'isFdaRegulatedDevice': False}, 'conditionsModule': {'conditions': ['Non-hodgkin Lymphoma', 'Hodgkin Lymphoma']}, 'descriptionModule': {'briefSummary': '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).', 'detailedDescription': '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.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '39 Years', 'minimumAge': '3 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* 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:\n\nCOHORT I:\n\nBurkitt 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)\n\nCOHORT Ia: stage III with LDH ≥ 2 ULN OR stage IV (5-24% bone marrow lymphoma infiltration) (GROUP B)61\n\nCOHORT 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).\n\nCOHORT II Classical Hodgkin lymphoma (ICD-O 9650/3, 9663/3, 9651/3, 9652/3, 9653/3)\n\nCOHORT IIa: stage I-IIA with bulky ± E, I-IIB no bulky ± E, IIIA ± E (INTERMEDIATE RISK)\n\nCOHORT IIb: stage IIB with bulky ± E, IIIA with bulky ± E, IIIB, IV (HIGH RISK)\n\n* Adequate organ function\n\nExclusion Criteria:\n\n* Primary mediastinal B-cell lymphoma (PMBL)\n* T-cell/histiocyte-rich large B-cell lymphoma\n* Gray zone lymphoma\n* Follicular lymphoma\n* Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL)\n* Posttransplant lymphoproliferative lymphoma (PTLD)'}, 'identificationModule': {'nctId': 'NCT05253495', 'acronym': 'RADICAL', 'briefTitle': 'Chemoradiotherapy With Targeted Immunotherapy in Pediatric Lymphoma', 'organization': {'class': 'OTHER', 'fullName': 'New York Medical College'}, 'officialTitle': 'Reducing the Burden of Oncologic Chemoradiotherapy And Radiation Exposure From Diagnostic Imaging by Utilizing Targeted Immunotherapy in Children, Adolescents and Young Adults With Lymphoma', 'orgStudyIdInfo': {'id': '14601'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Cohort 1a', '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).\n\nCohort 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).', 'interventionNames': ['Drug: DOC Group B', 'Drug: Pv-COMRAD 1 and 2 Group B', 'Drug: Pv-R-CYM 1 and 2 Group B']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 1b', '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.', 'interventionNames': ['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', 'Radiation: Involved Site Radiation Therapy']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 2a', '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.', 'interventionNames': ['Drug: Bv-AVD-R 1 and 2: COHORT IIa', 'Drug: Bv-NVD-R, Cycle 1-2', 'Drug: Bv-NVD-R, Cycle 1-4 SER']}, {'type': 'EXPERIMENTAL', 'label': 'Cohort 2b', '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.', 'interventionNames': ['Drug: Bv-AVD-R', 'Drug: Bv-NVD-R, Cycle 1-4 RER', 'Drug: Bv-NAVD-R, Cycle 1-2', 'Radiation: Involved Site Radiation Therapy']}], 'interventions': [{'name': 'DOC Group B', 'type': 'DRUG', 'otherNames': ['Reduction Phase'], 'description': 'Cyclophosphamide 300 mg x1; dexamethasone x 7; vincristine x1', 'armGroupLabels': ['Cohort 1a']}, {'name': 'Pv-COMRAD 1 and 2 Group B', 'type': 'DRUG', 'otherNames': ['Induction 1 and 2'], 'description': 'polatuzumab vedotin x1; dexamethasone x 5; vincristine x1, cyclophosphamide x 3; doxorubicin x1; methotrexate x; rituximab 2x; ITT x1', 'armGroupLabels': ['Cohort 1a']}, {'name': 'Pv-R-CYM 1 and 2 Group B', 'type': 'DRUG', 'otherNames': ['Consolidation 1 and 2'], 'description': 'polatuzumab vedotin x 1; methotrexate x 1; rituximab x 1; cytarabine x 5;', 'armGroupLabels': ['Cohort 1a']}, {'name': 'DOC Group C', 'type': 'DRUG', 'otherNames': ['Reduction with IT'], 'description': 'cyclophosphamide x 1, dexamethasone x 5; vincristine x1; IT triples x 3', 'armGroupLabels': ['Cohort 1b']}, {'name': 'MAD CPR 1 and 2', 'type': 'DRUG', 'otherNames': ['Induction 1 and 2 Group C'], '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', 'armGroupLabels': ['Cohort 1b']}, {'name': 'Pv-R CYVE 1 and 2', 'type': 'DRUG', 'otherNames': ['Consolidation 1 and 2 Group C CNS Negative'], 'description': 'Polatuzumab Vedotin x 1; Rituximab x 1; Cytarabine x 5; Etoposide x4;', 'armGroupLabels': ['Cohort 1b']}, {'name': 'Pv-R CYVE-MTX 1 and 2', 'type': 'DRUG', 'otherNames': ['Consolidation 1 and 2 Group C CNS Positive'], '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)', 'armGroupLabels': ['Cohort 1b']}, {'name': 'MAD CP', 'type': 'DRUG', 'otherNames': ['Maintenance 1 Group C'], 'description': 'dexamethasone x1; polatuzumab vedotin x 1; cyclophosphamide x 2; doxorubicin x 1; high dose methotrexate x 1; IT triples x 1', 'armGroupLabels': ['Cohort 1b']}, {'name': 'Pv-Cytarabine/etoposide', 'type': 'DRUG', 'otherNames': ['Maintenance 2, 4 Group C'], 'description': 'polatuzumab vedotin x 1; cytarabine x 5; etoposide x 3;', 'armGroupLabels': ['Cohort 1b']}, {'name': 'AD CP', 'type': 'DRUG', 'otherNames': ['Maintenance 3 Group C'], 'description': 'polatuzumab vedotin x 1; cyclophosphamide x2; doxorubicin x 2;', 'armGroupLabels': ['Cohort 1b']}, {'name': 'Bv-AVD-R 1 and 2: COHORT IIa', 'type': 'DRUG', 'otherNames': ['Intermediate Risk cohort IIa'], 'description': 'brentuximab vedotin x 2; doxorubicin x 2; vinblastine x 2; dacarbazine 2x; rituximab x 2', 'armGroupLabels': ['Cohort 2a']}, {'name': 'Bv-NVD-R, Cycle 1-2', 'type': 'DRUG', 'otherNames': ['Cohort IIa Rapid Early Responders'], 'description': 'brentuximab vedotin x 2; nivolumab x 2; vinblastine x2; dacarbazine x 2; rituximab x 2;', 'armGroupLabels': ['Cohort 2a']}, {'name': 'Bv-NVD-R, Cycle 1-4 SER', 'type': 'DRUG', 'otherNames': ['Cohort IIa Slow Early Responders'], 'description': 'brentuximab vedotin x 2; nivolumab x 2; vinblastine x 2; rituximab x 2;', 'armGroupLabels': ['Cohort 2a']}, {'name': 'Bv-AVD-R', 'type': 'DRUG', 'otherNames': ['High-Risk cohort IIb'], 'description': 'Brentuximab vedotin x2; doxorubicin x2; vinblastine x 2; dacarbazine x 2; rituximab x2;', 'armGroupLabels': ['Cohort 2b']}, {'name': 'Bv-NVD-R, Cycle 1-4 RER', 'type': 'DRUG', 'otherNames': ['cohort IIb Rapid Early Responders'], 'description': 'brentuximab vedotin x 2; nivolumab x 2; vinblastine x 2; dacarbazine x 2; rituximab x 2;', 'armGroupLabels': ['Cohort 2b']}, {'name': 'Bv-NAVD-R, Cycle 1-2', 'type': 'DRUG', 'otherNames': ['cohort IIb Slow Early Responders'], 'description': 'brentuximab vedotin x 2; nivolumab x 2; doxorubicin x 2; vinblastine x 2; dacarbazine x 2; rituximab x 2;', 'armGroupLabels': ['Cohort 2b']}, {'name': 'Involved Site Radiation Therapy', 'type': 'RADIATION', 'otherNames': ['Cohort II ONLY'], '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.', 'armGroupLabels': ['Cohort 1b', 'Cohort 2b']}]}, 'contactsLocationsModule': {'locations': [{'zip': '35233', 'city': 'Birmingham', 'state': 'Alabama', 'status': 'NOT_YET_RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Ana Xavier, MD', 'role': 'CONTACT', 'email': 'axavier@peds.uab.edu'}], 'facility': 'University of Alabama', 'geoPoint': {'lat': 33.52066, 'lon': -86.80249}}, {'zip': '32610', 'city': 'Gainsville', 'state': 'Florida', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'William Slayton, MD', 'role': 'CONTACT', 'email': 'slaytwb@peds.ufl.edu'}], 'facility': 'University of Flordia'}, {'zip': '10595', 'city': 'Vallhala', 'state': 'New York', 'status': 'RECRUITING', 'country': 'United States', 'contacts': [{'name': 'Mitchell S Cairo, MD', 'role': 'CONTACT', 'email': 'mitchell_cairo@nymc.edu', 'phone': '914-594-2150'}, {'name': 'Mitchell S. Cairo, MD', 'role': 'PRINCIPAL_INVESTIGATOR'}], 'facility': 'New York Medical College'}], 'centralContacts': [{'name': 'Mitchell Cairo, MD', 'role': 'CONTACT', 'email': 'mitchell_cairo@nymc.edu', 'phone': '9145942150'}, {'name': 'Lauren Harrison, RN', 'role': 'CONTACT', 'email': 'lauren_harrison@nymc.edu', 'phone': '617-285-7844'}], 'overallOfficials': [{'name': 'Mitchell Cairo, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'New York Medical Center'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'New York Medical College', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Principal Investigator', 'investigatorFullName': 'Mitchell Cairo', 'investigatorAffiliation': 'New York Medical College'}}}}