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Clinical Trials (PDQ®)

Phase II Randomized Pilot Study of Pegaspargase vs Native E. coli Asparaginase in the Standard Treatment Arm of Protocol CCG-1952 for Standard-Risk Acute Lymphoblastic Leukemia
Last Modified: 2/5/2010  

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

Alternate Title

Comparison of Two Forms of Asparaginase in Treating Children With Previously Untreated Acute Lymphoblastic Leukemia

Basic Trial Information

PhaseTypeStatusAgeSponsorProtocol IDs
Phase IITreatmentClosed1 to 9NCICCG-1962

Objectives

I.  Compare the safety of pegaspargase vs. native E. coli asparaginase 
administered during Induction and phases 1 and 2 of Delayed Intensification of 
the standard treatment arm on protocol CCG-1952 in children with newly 
diagnosed, standard-risk acute lymphocytic leukemia.

II.  Determine whether the incidence of high-titer anti-asparaginase 
antibodies in children treated with pegaspargase is decreased by at least 50% 
compared to children treated with native E. coli asparaginase during phases 1 
and 2 of Delayed Intensification.

III.  Determine the length of time that serum asparaginase levels remain above 
0.03 IU/microliter and that the serum asparagine concentration remains above 1 
micromolar in children treated with pegaspargase vs. native E. coli 
asparaginase.

IV.  Compare pharmaco-economic data from PEG-asparaginase with native E. 
coli-asparaginase in induction and both delayed induction phases.

Entry Criteria

Disease Characteristics:


Newly diagnosed acute lymphoblastic leukemia (ALL)

No more than 25% L3 lymphoblasts in marrow

Initial white blood cell count less than 50,000/mm3 (performed at CCG
institution)

Massive lymphadenopathy, massive splenomegaly, or large mediastinal mass
allowed

CNS or testicular leukemia allowed


Prior/Concurrent Therapy:


No prior treatment for ALL

Biologic therapy:
  Not specified

Chemotherapy:
  Intrathecal cytarabine (IT ARA-C) may begin prior to registration provided
  systemic chemotherapy initiated within 72 hours afterwards

Endocrine therapy:
  See Radiotherapy
  At least 1 month since systemic corticosteroids
     Steroids given for less than 48 hours allowed
  Inhaled corticosteroids allowed at any time

Radiotherapy:
  Radiotherapy or dexamethasone for mediastinal mass causing superior
  mediastinal syndrome allowed prior to registration, if indicated

Surgery:
  Not specified


Patient Characteristics:


Age:
  1 through 9


Expected Enrollment

A total of 116 patients will be accrued for this study over 18 months.

Outline

This is a randomized study.  Patients are stratified by randomizing 
institution.

All patients receive Induction with prednisone on days 0-27 and vincristine 
weekly for 4 weeks.  One group of patients receives pegaspargase on day 3, 
while a second group of patients receives native E. coli asparaginase three 
times per week for 3 weeks, beginning on day 2, 3, or 4.

Consolidation begins on day 28 of Induction, with prednisone tapered over 10 
days, vincristine given on day 0, and mercaptopurine given on days 1-27.  
Patients then receive Interim Maintenance 1 with prednisone on days 0-4 and 
28-32, vincristine on days 0 and 28, methotrexate weekly through day 49, and 
mercaptopurine on days 0-49.

Delayed Intensification 1 begins on day 56 of Interim Maintenance 1, with 
dexamethasone on days 0-6 and 14-20, vincristine and doxorubicin on days 0, 7, 
and 14, cyclophosphamide on day 28, thioguanine on days 28-41, and cytarabine 
on days 29-32 and 36-39.  Patients in the first group receive pegaspargase on 
day 3, while those in the second group receive native E. coli asparaginase 
three times per week for 2 weeks, beginning on day 2, 3, or 4.

Interim Maintenance 2 begins on day 56 of Delayed Intensification 1, with 
prednisone on days 0-4 and 28-32, vincristine on days 0 and 28, methotrexate 
weekly through day 49, and mercaptopurine on days 0-49.

Delayed Intensification 2 begins on day 56 of Interim Maintenance 2 and is 
identical to Delayed Intensification 1.

Maintenance begins on day 56 of Delayed Intensification 2, with prednisone on 
days 0-4, 28-32, and 56-60; vincristine on days 0, 28, and 56; mercaptopurine 
on days 0-83; and methotrexate weekly through day 77.  Maintenance courses 
repeat every 84 days and continue, in the absence of progression, for 2 
calendar years from the beginning of Interim Maintenance 1 for girls and for 3 
calendar years for boys.

CNS therapy/prophylaxis consists of intrathecal cytarabine/methotrexate during 
Induction and intrathecal methotrexate during Consolidation, Delayed 
Intensification 1 and 2, and Maintenance.  Patients with CNS leukemia at 
diagnosis receive craniospinal irradiation at the beginning of Consolidation; 
those with testicular disease receive bilateral testicular irradiation during 
Consolidation.

Patients are followed every 6-8 weeks for 1 year, every 3 months for 1 year, 
every 6 months for 1 year, then yearly.

Published Results

Avramis VI, Sencer S, Periclou AP, et al.: A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children's Cancer Group study. Blood 99 (6): 1986-94, 2002.[PUBMED Abstract]

Kurre HA, Ettinger AG, Veenstra DL, et al.: A pharmacoeconomic analysis of pegaspargase versus native Escherichia coli L-asparaginase for the treatment of children with standard-risk, acute lymphoblastic leukemia: the Children's Cancer Group study (CCG-1962). J Pediatr Hematol Oncol 24 (3): 175-81, 2002 Mar-Apr.[PUBMED Abstract]

Avramis VI, Holcenberg JS, Ettinger AG, et al.: Failure of asparagine (ASN) depletion, not inadequate asparaginase (ASNase) activity, predicts relapse in standard risk (SR) childhood acute lymphoblastic leukemia (ALL): a Children's Oncology Group (COG) report. [Abstract] Blood 110 (11): A-588, 2007.

Avramis IA, Panosyan EH, Dorey F, et al.: Vascular endothelial growth factor (VEGF-A) serum levels in standard risk ALL pediatric patients (CCG-1962 study). [Abstract] J Clin Oncol 24 (Suppl 18): A-9026, 508s, 2006.

Avramis IA, Panosyan EH, Dorey F, et al.: Correlation between high vascular endothelial growth factor-A serum levels and treatment outcome in patients with standard-risk acute lymphoblastic leukemia: a report from Children's Oncology Group Study CCG-1962. Clin Cancer Res 12 (23): 6978-84, 2006.[PUBMED Abstract]

Avramis VI, Panosyan EH, Avramis IA, et al.: Pharmacodynamic relationships between asparagine INPUT (Imax) post asparaginase (ASNase) therapy and outcome in SR ALL patients (CCG-1962). [Abstract] J Clin Oncol 24 (Suppl 18): A-9025, 508s, 2006.

Avramis VI, Panosyan EH, Fu CH, et al.: Pharmacodynamic (PD) analyses of asparagine (Asn) deamination and asn input (Imax) in serum of pediatric patients with standard risk acute lymphoblastic leukemia (SR ALL) receiving native or pegylated E. coli asparaginases (ASNase) (CCG-1962). [Abstract] Blood 104 (11): A-2082, 2004.

Related Publications

Nguyen K, Devidas M, Cheng SC, et al.: Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group study. Leukemia 22 (12): 2142-50, 2008.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

Children's Cancer Group

John Holcenberg, MD, Protocol chair
Ph: 206-987-2106
Email: john.holcenberg@seattlechildrens.org

Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol.