Chemoradiotherapy With Targeted Immunotherapy in Pediatric Lymphoma

Part of paid clinical trials in Birmingham, Alabama.

Sponsor
New York Medical College
Study ID
NCT05253495
Phase
PHASE2
Status
Recruiting
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Conditions

Eligibility Criteria

Sex
ALL
Age
3 Years - 39 Years
Healthy Volunteers
Not accepted

Interventions

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

Study Details

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).

Key Dates

Start date
Feb 1, 2022
Status verified
Jun 2025
Primary completion
Dec 31, 2027
Completion
Jun 30, 2028

Study Design

Enrollment
80 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Cohort 1a
    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).
  • Experimental: Cohort 1b
    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.
  • Experimental: Cohort 2a
    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.
  • Experimental: Cohort 2b
    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.

Primary Outcome Measure

Grade 3 and 4 Adverse Events related to polatuzumab vedotin [ Time Frame: 1 year ]

Central Contacts

Locations (3)

FacilityCityStateZIPSite coordinators
University of AlabamaBirminghamAlabama35233
Ana Xavier, MD
[email protected]
University of FlordiaGainsvilleFlorida32610
William Slayton, MD
[email protected]
New York Medical CollegeVallhalaNew York10595
Mitchell S Cairo, MD
[email protected]
914-594-2150
Mitchell S. Cairo, MD (PRINCIPAL_INVESTIGATOR)

Find similar trials in Birmingham, AL

By research site
University of Alabama· Birmingham, ALUniversity of Flordia· Gainsville, FLNew York Medical College· Vallhala, NY

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