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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort 1a | Experimental | 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). |
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| Cohort 1b | Experimental | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DOC Group B | Drug | Cyclophosphamide 300 mg x1; dexamethasone x 7; vincristine x1 |
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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 |
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Inclusion Criteria:
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)
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Mitchell Cairo, MD | Contact | 9145942150 | mitchell_cairo@nymc.edu | |
| Lauren Harrison, RN | Contact | 617-285-7844 | lauren_harrison@nymc.edu |
| Name | Affiliation | Role |
|---|---|---|
| Mitchell Cairo, MD | New York Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama | Not yet recruiting | Birmingham | Alabama | 35233 | United States |
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| Cohort 2a | Experimental | 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. |
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| Cohort 2b | Experimental | 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. |
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| Pv-COMRAD 1 and 2 Group B | Drug | polatuzumab vedotin x1; dexamethasone x 5; vincristine x1, cyclophosphamide x 3; doxorubicin x1; methotrexate x; rituximab 2x; ITT x1 |
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| Pv-R-CYM 1 and 2 Group B | Drug | polatuzumab vedotin x 1; methotrexate x 1; rituximab x 1; cytarabine x 5; |
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| DOC Group C | Drug | cyclophosphamide x 1, dexamethasone x 5; vincristine x1; IT triples x 3 |
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| MAD CPR 1 and 2 | Drug | 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 |
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| Pv-R CYVE 1 and 2 | Drug | Polatuzumab Vedotin x 1; Rituximab x 1; Cytarabine x 5; Etoposide x4; |
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| Pv-R CYVE-MTX 1 and 2 | Drug | 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) |
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| MAD CP | Drug | dexamethasone x1; polatuzumab vedotin x 1; cyclophosphamide x 2; doxorubicin x 1; high dose methotrexate x 1; IT triples x 1 |
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| Pv-Cytarabine/etoposide | Drug | polatuzumab vedotin x 1; cytarabine x 5; etoposide x 3; |
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| AD CP | Drug | polatuzumab vedotin x 1; cyclophosphamide x2; doxorubicin x 2; |
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| Bv-AVD-R 1 and 2: COHORT IIa | Drug | brentuximab vedotin x 2; doxorubicin x 2; vinblastine x 2; dacarbazine 2x; rituximab x 2 |
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| Bv-NVD-R, Cycle 1-2 | Drug | brentuximab vedotin x 2; nivolumab x 2; vinblastine x2; dacarbazine x 2; rituximab x 2; |
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| Bv-NVD-R, Cycle 1-4 SER | Drug | brentuximab vedotin x 2; nivolumab x 2; vinblastine x 2; rituximab x 2; |
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| Bv-AVD-R | Drug | Brentuximab vedotin x2; doxorubicin x2; vinblastine x 2; dacarbazine x 2; rituximab x2; |
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| Bv-NVD-R, Cycle 1-4 RER | Drug | brentuximab vedotin x 2; nivolumab x 2; vinblastine x 2; dacarbazine x 2; rituximab x 2; |
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| Bv-NAVD-R, Cycle 1-2 | Drug | brentuximab vedotin x 2; nivolumab x 2; doxorubicin x 2; vinblastine x 2; dacarbazine x 2; rituximab x 2; |
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| Involved Site Radiation Therapy | Radiation | 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. |
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| University of Flordia | Recruiting | Gainsville | Florida | 32610 | United States |
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| New York Medical College | Recruiting | Vallhala | New York | 10595 | United States |
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| ID | Term |
|---|---|
| D008228 | Lymphoma, Non-Hodgkin |
| D006689 | Hodgkin Disease |
| ID | Term |
|---|---|
| D008223 | Lymphoma |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
| D008232 | Lymphoproliferative Disorders |
| D008206 | Lymphatic Diseases |
| D006425 | Hemic and Lymphatic Diseases |
| D007160 | Immunoproliferative Disorders |
| D007154 | Immune System Diseases |
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| ID | Term |
|---|---|
| D005047 | Etoposide |
| ID | Term |
|---|---|
| D011034 | Podophyllotoxin |
| D013764 | Tetrahydronaphthalenes |
| D009281 | Naphthalenes |
| D011084 | Polycyclic Aromatic Hydrocarbons |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D011083 | Polycyclic Compounds |
| D005960 | Glucosides |
| D006027 | Glycosides |
| D002241 | Carbohydrates |
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