Treatment of Burkitt Lymphoma/Leukemia and B Large Cell NHL

Overview[ - collapse ][ - ]

Purpose 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.
ConditionNon-Hodgkin Lymphoma
Acute Lymphoblastic Leukemia, Mature B-Cell
InterventionDrug: Prednison, Vincristine, Cytarabine, Methotrexate, Etoposide, Cyclophosphamide, Doxorubicin
PhasePhase 2
SponsorSt. Jude Children's Research Hospital
Responsible PartySt. Jude Children's Research Hospital
ClinicalTrials.gov IdentifierNCT00187161
First ReceivedSeptember 13, 2005
Last UpdatedJune 3, 2008
Last verifiedJune 2008

Tracking Information[ + expand ][ + ]

First Received DateSeptember 13, 2005
Last Updated DateJune 3, 2008
Start DateNovember 1994
Estimated Primary Completion DateJanuary 2007
Current Primary Outcome MeasuresThe 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. [Time Frame: 8-9 years] [Designated as safety issue: Yes]
Current Secondary Outcome MeasuresNot Provided

Descriptive Information[ + expand ][ + ]

Brief TitleTreatment of Burkitt Lymphoma/Leukemia and B Large Cell NHL
Official TitleSmall Noncleaved Cell (SNCC), Non-Hodgkin Lymphoma (NHL), Large Cell NHL (B-Cell) and B-Cell Acute Lymphoblastic Leukemia (B-ALL) Study II
Brief Summary
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
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
Study TypeInterventional
Study PhasePhase 2
Study DesignAllocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition
  • Non-Hodgkin Lymphoma
  • Acute Lymphoblastic Leukemia, Mature B-Cell
InterventionDrug: Prednison, Vincristine, Cytarabine, Methotrexate, Etoposide, Cyclophosphamide, Doxorubicin
The additional information is contained in the Detailed Description section.
Study Arm (s)
  • Experimental: A
    Group A: Resected Stage I and resected abdominal Stage II
    Subjects will receive two courses (3 weeks apart) of COPAD.
  • Experimental: B
    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.
  • Experimental: C
    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.

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment68
Estimated Completion DateJanuary 2007
Estimated Primary Completion DateNot Provided
Eligibility Criteria
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
GenderBoth
AgesN/A
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesUnited States

Administrative Information[ + expand ][ + ]

NCT Number NCT00187161
Other Study ID NumbersSJBCII
Has Data Monitoring CommitteeNo
Information Provided BySt. Jude Children's Research Hospital
Study SponsorSt. Jude Children's Research Hospital
CollaboratorsNot Provided
Investigators Principal Investigator: John T. Sandlund, M.D. St. Jude Children's Research Hospital
Verification DateJune 2008

Locations[ + expand ][ + ]

St. Jude Children's Research Hospital
Memphis, Tennessee, United States, 38105