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

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II	Treatment	Completed	over 18	NCI	CLB-9013 CALGB-9013

Objectives

I.  Determine whether the combination of low-dose cytarabine and interferon 
alpha can reduce or eliminate Philadelphia chromosome-positive cells in 
previously untreated patients with chronic phase CML.
II.  Assess the response rate, duration of response, and survival of patients 
with chronic phase CML treated with this regimen.
III.  Define the safety and toxicities of this treatment for CML patients.
IV.  Assess the proposed new guidelines for clearly defining chronic phase CML 
by comparing the outcome of patients in blast crisis with those having 
aggressive disease (as defined by Karanas and Silver and Gralnick and Bennett).
V.  Determine, in conjunction with protocol CLB-8761, whether quantitative 
measurements of the breakpoint cluster region (bcr) test are comparable to 
cytogenetic analysis and correlate with clinical parameters in the management 
of patients on this treatment regimen.
VI.  Determine, in conjunction with protocol CLB-8761 and in a large-sample 
prospective manner, whether the location of the chromosome 22 breakpoint 
within the bcr, as determined by fine gene mapping, accounts for variability 
in disease duration.
VII.  Investigate, in conjunction with protocol CLB-8761, the concordance of 
Ph(-) and Ph(+) cells between blood and bone marrow as remission is achieved 
on this regimen.

Entry Criteria

Disease Characteristics:

Chronic phase CML with diagnosis established by all of the
following:
  Unexplained peripheral blood leukocytosis

  Myeloid hyperplasia and less than 20% myeloblasts plus
  promyelocytes on bone marrow aspirate

  Philadelphia chromosome positive (banded, bone marrow
  cytogenetic studies required in all patients)

Concurrent registration on protocol CLB-8761 (molecular
genetics of CML) required

Prior/Concurrent Therapy:

Biologic therapy:
  No prior interferon

Chemotherapy:
  No prior chemotherapy, including hydroxyurea

Endocrine therapy:
  Not specified

Radiotherapy:
  No prior radiotherapy

Surgery:
  More than 4 weeks since major surgery
  More than 2 weeks since minor surgery

Patient Characteristics:

Age:
  Over 18

Performance status:
  CALGB 0-2

Life expectancy:
  At least 2 years

Hematopoietic:
  Platelets greater than 100,000

Hepatic:
  Bilirubin less than 1.5 x normal
  SGOT/SGPT less than 1.5 x normal
  Alkaline phosphatase less than 1.5 x normal (unless elevation
     presumed due to CML)
  PT/PTT less than 1.5 x normal

Renal:
  Creatinine less than 1.8 mg/dl

Cardiovascular:
  No significant cardiovascular risk history, e.g.:
   No NYHA class III/IV
   No myocardial infarction within 1 year
   No ventricular arrhythmias (except PVCs)

Other:
  No other serious medical or psychiatric illness that would
  prevent informed consent or require therapy

  No second malignancy within 5 years except:
     Inactive nonmelanomatous skin cancer
     In situ cervical cancer

  No pregnant women
  Effective contraception required while on protocol

Expected Enrollment

80 patients will be entered to provide 75 evaluable patients.

Outline

Nonrandomized study.
Single-agent Chemotherapy plus Biological Response Modifier Therapy.  
Cytarabine, ARA-C, NSC-63878; plus Interferon alpha-2b (Schering), IFN-A, 
NSC-377523.

Farag SS, Ruppert AS, Mrózek K, et al.: Prognostic significance of additional cytogenetic abnormalities in newly diagnosed patients with Philadelphia chromosome-positive chronic myelogenous leukemia treated with interferon-alpha: a Cancer and Leukemia Group B study. Int J Oncol 25 (1): 143-51, 2004.[PUBMED Abstract]

Silver RT, Peterson BL, Szatrowski TP, et al.: Treatment of the chronic phase of chronic myeloid leukemia with an intermittent schedule of recombinant interferon alfa-2b and cytarabine: results from CALGB study 9013. Leuk Lymphoma 44 (1): 39-48, 2003.[PUBMED Abstract]

Silver RT, Peterson BL, Szatrowski TP, et al.: Treatment of chronic myeloid leukemia (CML) with an intermittent schedule of interferon α-B. [Abstract] Proceedings of the American Society of Clinical Oncology 20: A-1222, 2001.

Hensley ML, Peterson B, Silver RT, et al.: Risk factors for severe neuropsychiatric toxicity in patients receiving interferon alfa-2b and low-dose cytarabine for chronic myelogenous leukemia: analysis of Cancer and Leukemia Group B 9013. J Clin Oncol 18 (6): 1301-8, 2000.[PUBMED Abstract]

Hensley ML, Silver RT, Peterson BL, et al.: Risk factors for severe neuropsychiatric toxicity (NPtox) in patients receiving interferon-alfa-2b (rIFN-a) and low-dose cytarabine (AraC) for chronic myeloid leukemia (CML): analysis of CALGB 9013. [Abstract] Proceedings of the American Society of Clinical Oncology 18: A1604, 1999.

Trial Contact Information

Trial Lead Organizations

Cancer and Leukemia Group B

Richard Silver, MD, Protocol chair		Ph: 212-746-2855 Email: rtsilve@mail.med.cornell.edu