Treatment of Burkitt Lymphoma/Leukemia and B Large Cell NHL

Non-Hodgkin Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00187161
• Other study ID #: SJBCII
• Status: Completed
• Phase: Phase 2
• First received: September 13, 2005
• Last updated: June 3, 2008
• Start date: November 1994
• Est. completion date: January 2007

Study information

• Verified date: June 2008
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: January 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 18 Years

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia, Mature B-Cell
• Burkitt Lymphoma
• Leukemia
• Leukemia, Lymphoid
• Lymphoma
• Lymphoma, Non-Hodgkin
• Non-Hodgkin Lymphoma
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Prednison, Vincristine, Cytarabine, Methotrexate, Etoposide, Cyclophosphamide, Doxorubicin
The additional information is contained in the Detailed Description section.

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes

External Links

•   St. Jude Children's Research Hospital