Treatment of Burkitt Lymphoma/Leukemia and B Large Cell NHL

Study Overview
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Brief Summary
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This is a pilot study to demonstrate that the modified LMB-89 treatment regimen for children with newly diagnosed small noncleaved cell NHL, large cell NHL (B-cell), and B-cell acute lymphoblastic leukemia can be delivered in this setting with acceptable toxicity.

Detailed Description
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Group A: Resected Stage I and resected abdominal Stage II Subjects will receive two courses (3 weeks apart) of COPAD as follows: Cyclophosphamide (CTX) 500 mg/m2/day (divided q12 hrs) IV day 1, 2, 3 Vincristine (VCR) 2 mg/m2 (max 2.0 mg) IV day 1, 6 Prednisone 60 mg/m2/d (divided bid) PO day 1-5 Adriamycin 60 mg/m2 over 6 hrs IV day 1 GCSF 5 mcg/kg/day SQ will be given once a day starting on day 7 until blood counts recover. Group B: Other Stage II, Stage III, Stage IV or B-ALL M blast <70%; no CNS involvement. Treatment Pre-Induction Subjects in Group B will receive one week of treatment of COP as follows: CTX 300 mg/m2 IV day 1; VCR 1 mg/m2 (max 2.0 mg) IV day 1; Prednisone 60 mg/m2/day (divided bid) PO day 1-7; Methotrexate (MTX) and hydrocortisone (HC) into the spinal fluid (IT), each age adjusted, day 1; Induction -COPADM x 2 (COPAD M3 #1 (starting day 8 COP if greater than or equal to 20% reduction in tumor size by day 7 COP; if <20% then proceed to Group C starting at COPADM8 No. 1); COPADM3 #1 VCR 2 mg/m2 (max 2 mg) IV day 1; High-dose (HD) MTX 3 gm/m2 IV (over 3 hrs) day 1; MTX and HC each age adjusted IT day 2, 6 CTX 500 mg/m2/day (divided q12 hrs) IV day 2, 3, 4; Adriamycin 60 mg/m2 over 6 hrs IV; day 2; Prednisone 60 mg/m2 (divided bid) po day 1-5. G-CSF 5 mcg/kg/day starting day 7 until counts recover. COPADM3 #2 Like COPADM #1 (above) except: CTX - double dose (1 gm/m2/day) (divided q12 hr) VCR - second dose given on day 6 Consolidation- CYM x 2 courses HDMTX 3 gm/m2 (over 3 hr) IV Day 1; MTX plus HC each age adjusted IT day 2; Cytarabine (Ara-C) 100 mg/m2/day CI/IV (x 5 days) day 2-6; Ara-C and HC each age adjusted IT day 7. Maintenance Sequence 1 Prednisone 60 mg/m2/d (divided bid) PO day 1-5; HDMTX 3 gm/m2 (over 3 hr) IV Day 1; MTX plus HC each age adjusted IT day 2; CTX 500 mg/m2/day IV day 2, 3; Adriamycin 60 mg/m2 (over 6 hrs) IV day 3; VCR 2 mg/m2 (max 2 mg) IV day 1. G-CSF 5 mcg/kg/day starting day 6 until counts recover. Group C: B-ALL with >70% BM blasts; CNS involvement, Group B COP failures i.e., <20% reduction Treatment Pre-Induction Subjects will receive one week of treatment of COP as follows: CTX 300 mg/m2 IV day 1 VCR 1 mg/m2 (max 2 mg) IV day 1 Prednisone 60 mg/m2/d (divided) bid po day 1-7 MTX + HC + Ara-C each age adjusted IT day 1, 3, 5 Leucovorin 15 mg/m2 q12 hr x 2 po day 2, 4 Induction-COPADM x 2 Subjects will begin induction therapy the day after COP is finished as follows: COPADM8#1 VCR 2 mg/m2 (max 2 mg) IV day 1; HD MTX 8 gm/m2 (over 4 hrs) IV Day 1; MTX+HC+Ara-C each age adjusted IT day 1, 4, 6 (Ommaya, day 1); CTX 500 mg/m2/day divided every 12 hours IV day 2, 3, 4; Adriamycin 60 mg/m2 (over 6 hrs) IV day 2; Prednisone 60 mg/m2/day (divided bid) po/IV day 1-5. G-CSF 5 mcg/kg/day starting day 7 until counts recover. COPADM8 #2 Like COPAD M8 #1 except: CTX-double dose (1 gm/m2/day) (divided q12hs) IV VCR - 2nd dose given on day 6 Consolidation - CYVE x 2 courses Ara-C 50 mg/m2/12 hrs CI/IV Day 1-5; HD Ara-C 3 gm/m2/day IV over 3 hours Day 2-5; VP-16 200 mg/m2/day IV over 2 hours Day 2-5. Maintenance: Subjects will receive four courses of chemotherapy during continuation. Each course will use different chemotherapy drugs. Sequence 1 Prednisone 60 mg/m2/day (divided bid) po/IV day 1-5; HD MTX 8 gm/m2 (over 4 hrs) IV Day 1; MTX+HC+Ara-C each age adjusted IT day 2 (Ommaya, day 2) CTX 500 mg/m2 IV day 2, 3; Adriamycin 60 mg/m2 (over 6 hrs) IV day 3; VCR 2 mg/m2 (max 2 mg) IV day 1. G-CSF 5 mcg/kg/day starting day 7 until counts recover. Sequence 2 Ara-C 100 mg/m2/day (divided q12 hrs) SQ Day 1-5; VP-16 150 mg/m2/day (over 2 hrs) IV Days 1-3; G-CSF 5 micro g/kg SQ Days 6 until counts recovery; MTX+HC+Ara-C each age adjusted IT Day 1 (CNS positive, only) Ommaya Day 1 (CNS positive, only) Sequence 3 Prednisone 60 mg/m2/day (divided bid) po day 1-5; CTX 500 mg/m2/day IV day 1, 2; Adriamycin 60 mg/m2 (over 6 hrs) IV day 2; VCR 2 mg/m2 (max 2 mg) IV day 1; G-CSF 5 mcg/kg SQ starting day 6 until counts recover; MTX+HC+Ara-C each age adjusted IT Day 1 (CNS positive, only) Ommaya Day 1 (CNS positive, only). Sequence 4 Ara-C 100 mg/m2/day (divided q12 hrs) SQ Day 1-5; VP-16 150 mg/m2/day (over 2 hrs) IV Days 1-3; G-CSF 5 mcg/kg SQ days 6 until counts recover; MTX+HC+Ara-C each age adjusted IT Day 1 (CNS positive, only) Ommaya Day 1 (CNS positive, only) Intrathecal (IT) Treatment doses and volume are as follows: < than 1 year, MTX 8 mg, HC 8 mg, Ara C 15 mg, Volume 8 ml; Age 12-23 mo, MTX 10 mg, HC 10 mg, Ara C 20 mg, Volume 10 ml; Age 24-35 mo, MTX 12 mg, HC 12 mg, Ara C 25 mg, Volume 12 ml; Age ≥3 yr, MTX 15 mg, HC 15 mg, Ara C 30 mg. Volume 15 ml Ommaya Reservoir Treatment (CNS positive only) Age ≥3 yr, MTX 6 mg, HC 15 mg, Ara C 50 mg/m2 (50 mg max) Volume 3 ml

Official Title
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Small Noncleaved Cell (SNCC), Non-Hodgkin Lymphoma (NHL), Large Cell NHL (B-Cell) and B-Cell Acute Lymphoblastic Leukemia (B-ALL) Study II

Conditions
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Non-Hodgkin Lymphoma, Acute Lymphoblastic Leukemia, Mature B-Cell

Intervention / Treatment
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* Drug: Prednison, Vincristine, Cytarabine, Methotrexate, Etoposide, Cyclophosphamide, Doxorubicin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject must be previously untreated, except for steroids. Subject must be less than or equal to 18 years of age. Subject must have a histologic diagnosis of small noncleaved cell (SNCC) NHL or large cell NHL (B-cell), or B-cell acute lymphocytic leukemia. Exclusion Criteria: Previously treated disease

Ages Eligible for Study
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Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>Group A: Resected Stage I and resected abdominal Stage II Subjects will receive two courses (3 weeks apart) of COPAD. | Drug: Prednison, Vincristine, Cytarabine, Methotrexate, Etoposide, Cyclophosphamide, Doxorubicin<br>* The additional information is contained in the Detailed Description section.<br>|
| Experimental: B<br>Group B: Other Stage II, Stage III, Stage IV or B-ALL M blast <70%; no CNS involvement. Subjects in Group B will receive one week of treatment of COP. | Drug: Prednison, Vincristine, Cytarabine, Methotrexate, Etoposide, Cyclophosphamide, Doxorubicin<br>* The additional information is contained in the Detailed Description section.<br>|
| Experimental: C<br>Group C: B-ALL with >70% BM blasts; CNS involvement, Group B COP failures i.e., <20% reduction Treatment Pre-Induction Subjects will receive one week of treatment of COP. | Drug: Prednison, Vincristine, Cytarabine, Methotrexate, Etoposide, Cyclophosphamide, Doxorubicin<br>* The additional information is contained in the Detailed Description section.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The purpose of this study is estimate the complete response, event-free survival, and overall survival in patients with small non-cleaved cell non-Hodgkin lymphoma or large cell NHL, or Burkitt leukemia/B-cell ALL treated with a modified LMP-89 regimen. |  | 8-9 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mature B-Cell Leukemia, Non-Hodgkin Lymphoma, Burkitt's lymphoma, Small noncleaved cell non Hodgkin lymphoma, Large cell lymphoma