Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Published Results
Trial Contact Information
Registry Information

Alternate Title

Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma or Acute Lymphocytic Leukemia

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Closed	15 and over	NCI	CLB-9251 NCT00002494, CALGB-9251

Objectives

I.  Determine the response rate and disease free survival of HIV seronegative 
patients with diffuse small noncleaved cell lymphoma or L3 acute lymphocytic 
leukemia when treated with high intensity, brief duration combination 
chemotherapy:  alternating courses of ifosfamide/cytarabine/etoposide and 
cyclophosphamide/doxorubicin, each with methotrexate/vincristine/dexamethasone.

II.  Determine the toxicity of these regimens in HIV negative patients.

Entry Criteria

Disease Characteristics:

Histologically documented diffuse small noncleaved cell lymphoma (category J
by IWF) of any stage
  Nodal or abdominal masses with less than 25% lymphoblasts in marrow are
  defined as lymphoma

OR

Histologically documented L3 acute lymphocytic leukemia (ALL)
  Greater than 25% lymphoblasts in marrow is defined as ALL, regardless of
  presence of bulky nodal disease

Lymphoma requirements include:
  Documentation of lymphadenopathy, splenomegaly, or hepatomegaly, presence or
  absence of abdominal masses, and presence or absence of B symptoms

  Measurable disease other than ascites and pleural effusions, bony disease,
  and CNS lesions
     Bidimensionally measurable mass on physical exam, x-ray, or CT, or MRI

     OR 

     Clearly defined hepatic mass greater than 3.5 cm on CT, MRI, or
     ultrasound considered to represent lymphoma

     OR

     Histologically documented hepatic lymphoma with the liver extending more
     than 5 cm below the costal margin on quiet respiration


ALL requirements include:
  Documentation of monoclonal surface immunoglobulin by surface
  immunophenotyping

  Lymph node biopsy strongly recommended for patients with obvious marrow
   involvement

  Disease labeled L3 but also manifested by lymphadenopathy must be evaluated
  as is lymphoma (see above)

Prior/Concurrent Therapy:

Biologic:
 No concurrent growth factors 

Chemotherapy:
 Not specified

Endocrine therapy:
 Not specified

Radiotherapy:
 No concurrent palliative radiotherapy

Surgery:
 Not specified

Other:
 No prior therapy

Patient Characteristics:

Age:
  15 and over

Performance status:
  Any status

Life expectancy:
  At least 2 years

Hematopoietic:
  Not specified

Hepatic:
  Bilirubin no greater than 1.5 times normal (unless further elevation is
   directly attributable to malignancy)

Renal:
  Creatinine no greater than 1.5 times normal (unless further elevation is
   directly attributable to malignancy)

Cardiovascular:
  No uncontrolled or severe cardiovascular disease, e.g.:
     No myocardial infarction within the past 6 months
     No congestive heart failure

Other:
  HIV negative
  No active, uncontrolled bacterial, viral, or fungal infection
  No active, uncontrolled duodenal ulcer
  No other serious medical illness
  No serious psychiatric condition that would preclude informed consent or
     protocol compliance
  No second malignancy within 5 years except:
     Curatively treated carcinoma in situ of the cervix
     Curatively treated basal cell carcinoma
  Not pregnant
  Effective contraception required of fertile patients

Expected Enrollment

A total of 26-45 lymphoma patients and 2-6 leukemia patients will be accrued 
for this study.

Outline

Patients are stratified by participating institution and disease type (diffuse 
small noncleaved cell lymphoma vs L3 ALL).

Patients receive cyclophosphamide IV over 5-10 minutes on days 1 through 5 and 
oral prednisone on days 1 through 7, followed by alternating courses of: 2) 
ifosfamide IV over 1 hour on days 8 through 12, methotrexate IV over 24 hours 
on day 8; leucovorin calcium IV over 36 hours after initiation of 
methotrexate, then IV (or orally as tolerated, after the first 24 hours) every 
6 hours until the serum methotrexate level is below 5 x 10 to the minus eighth 
M; vincristine IV on day 8; cytarabine IV over 48 hours and etoposide IV over 
60 minutes on days 11 and 12; and oral dexamethasone on days 8 through 12, 
plus triple intrathecal therapy (TIT) with methotrexate, cytarabine, and 
hydrocortisone on days 8 and 12, and 3) cyclophosphamide IV over 5-10 minutes 
on days 29 through 33; methotrexate IV over 24 hours and vincristine IV on day 
29; leucovorin calcium IV over 36 hours after initiation of methotrexate, then 
IV (or orally as tolerated, after the first 24 hours) every 6 hours until the 
serum methotrexate level is below 5 x 10 to the minus eighth M; doxorubicin IV 
on days 32 and 33; and oral dexamethasone on days 29 through 33, plus TIT on 
day 29, with doses as above.  

Patients with CNS disease at diagnosis continue TIT once weekly until the CSF 
clears, then weekly for 4 more weeks. TIT must be completed prior to 
initiation of radiotherapy. All patients must complete at least the first 3 
courses of chemotherapy. Courses 2 and 3 each repeat 3 times in the absence of 
disease progression or unacceptable toxicity. On days 134-139, patients who 
have had prior bone marrow involvement receive cranial radiation therapy. 
Patients who achieve less than a complete response and who have an HLA-matched 
sibling should undergo allogeneic bone marrow transplant on protocol CLB-9113. 

Patients are followed monthly for 6 months, every 2 months for 18 months, 
every 6 months for 2 years, and thereafter for survival.

Rizzieri DA, Johnson JL, Niedzwiecki D, et al.: Intensive chemotherapy with and without cranial radiation for Burkitt leukemia and lymphoma: final results of Cancer and Leukemia Group B Study 9251. Cancer 100 (7): 1438-48, 2004.[PUBMED Abstract]

Lee EJ, Petroni GR, Schiffer CA, et al.: Brief-duration high-intensity chemotherapy for patients with small noncleaved-cell lymphoma or FAB L3 acute lymphocytic leukemia: results of cancer and leukemia group B study 9251. J Clin Oncol 19 (20): 4014-22, 2001.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Edward Lee, MD, Protocol chair		Ph: 410-964-2212 Email: edward.lee@usoncology.com

Registry Information
Official Title		HIGH INTENSITY, BRIEF DURATION CHEMOTHERAPY FOR DIFFUSE SMALL NONCLEAVED CELL LYMPHOMA AND THE L-3 SUBTYPE OF ALL: A PILOT STUDY OF A MULTIDRUG REGIMEN
Trial Start Date		1992-05-12
Registered in ClinicalTrials.gov		NCT00002494
Date Submitted to PDQ		1992-05-12
Information Last Verified		2004-06-21
NCI Grant/Contract Number		U10-CA31946