Treatment of Burkitt Lymphoma/Leukemia and B Large Cell NHL
Treatment of Burkitt Lymphoma/Leukemia and B Large Cell NHL
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.
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:

 1. CTX - double dose (1 gm/m2/day) (divided q12 hr)

 2. 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:

 1. CTX-double dose (1 gm/m2/day) (divided q12hs) IV

 2. 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
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