Calaspargase Pegol or Pegaspargase and Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT00671034
First received: May 1, 2008
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

This randomized clinical trial is studying giving calaspargase pegol together with combination chemotherapy to see how well it works compared with giving pegaspargase together with combination chemotherapy in treating younger patients with newly diagnosed high-risk acute lymphoblastic leukemia. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more cancer cells.


Condition Intervention
B-cell Adult Acute Lymphoblastic Leukemia
B-cell Childhood Acute Lymphoblastic Leukemia
Untreated Adult Acute Lymphoblastic Leukemia
Untreated Childhood Acute Lymphoblastic Leukemia
Drug: calaspargase pegol
Drug: daunorubicin hydrochloride
Drug: doxorubicin hydrochloride
Drug: cytarabine
Drug: prednisone
Drug: methotrexate
Drug: cyclophosphamide
Drug: mercaptopurine tablet
Drug: dexamethasone
Drug: thioguanine
Drug: pegaspargase
Drug: vincristine sulfate
Radiation: radiation therapy
Other: laboratory biomarker analysis
Other: pharmacological study

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Intravenous EZN-2285 (SC-PEG E. Coli L-asparaginase, IND# 100594) or Intravenous Oncaspar® in the Treatment of Patients With High-Risk Acute Lymphoblastic Leukemia (ALL)

Resource links provided by NLM:


Further study details as provided by Children's Oncology Group:

Primary Outcome Measures:
  • Pharmacokinetics (PK) of SC-PEG E. coli L-asparaginase (EZN-2285) compared to pegaspargase during induction and consolidation therapy [ Time Frame: At baseline and days 4, 5, 6, 8, 15, 22 and 29 of induction, and days 15, 16, 17, 22, 29, 36 and 43 of consolidation ] [ Designated as safety issue: No ]
    For statistical comparisons and other analyses, study results of EZN-2285 2100 IU/m^2 and EZN-2285 2500 IU/m^2 will be tabulated separately, whereas results of Oncaspar® 2500 IU/m^2 throughout the entire study will be combined, unless otherwise specified. Descriptive statistics including mean, standard deviation, coefficient of variation, median, and minimum and maximum will be computed for each PK parameter for the induction and for the consolidation data. In addition, mean and median plasma concentration versus time graphs will be provided.


Secondary Outcome Measures:
  • Pharmacodynamics (PD) of EZN-2285 compared to pegaspargase during induction and consolidation therapy [ Time Frame: At baseline and days 4, 5, 6, 8, 15, 22 and 29 of induction, and days 15, 16, 17, 22, 29, 36 and 43 of consolidation ] [ Designated as safety issue: No ]
    Descriptive statistics including mean, standard deviation, coefficient of variation, median, and minimum and maximum will be computed for each PD parameter for the induction and for the consolidation data. The relationship between PK and PD results will be examined.

  • Minimal residual disease (MRD) [ Time Frame: At day 29 of induction therapy ] [ Designated as safety issue: No ]
    The observed negative MRD rates along with the corresponding 95% confidence interval (CI) will be determined per treatment arm after all patients complete their Consolidation therapy.

  • Complete remission (CR) rates [ Time Frame: At day 29 at the end of induction therapy ] [ Designated as safety issue: No ]
    CR rates along with the corresponding 95% CI will be determined per treatment arm after all patients complete their Consolidation therapy.

  • Event-free survival (EFS) [ Time Frame: From the date of diagnosis to the date of the first documented progression and/or relapse event (including induction failure), diagnosis of a second malignant neoplasm, or death from any cause, whichever comes first, assessed up to 5 years ] [ Designated as safety issue: No ]
    EFS estimates will be computed using the Kaplan-Meier product-limit method. Estimates of median EFS and the corresponding 95% CI will be calculated after minimum follow-up of 3 years. Correlation between end of Induction therapy MRD and EFS will be explored as appropriate.

  • Level of anti- EZN-2285 antibodies and anti- EZN-2285 neutralizing antibodies [ Time Frame: Up to day 29 of induction ] [ Designated as safety issue: No ]
    The incidence and level of anti- EZN-2285 antibodies and anti- EZN-2285 neutralizing antibodies will be summarized. The relation between the terminal PK of EZN-2285 and the presence of antibodies will be explored as appropriate.

  • Incidence of adverse events (AEs) as assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 [ Time Frame: Up to 5 years ] [ Designated as safety issue: Yes ]
    The calculation of AE incidence will be based on the number of patients per AE category. For each patient who has multiple AEs classified to the same category, that patient will be tabulated under the worst toxicity grade for that AE category. The incidence of AEs will be tabulated by treatment arm and by organ class. Special attention will be paid to hypersensitivity, pancreatitis, coagulopathy, infection, neurologic dysfunction and thromboembolic events.

  • Asparaginase immunogenicity [ Time Frame: Up to week 24 of maintenance therapy ] [ Designated as safety issue: No ]

Enrollment: 166
Study Start Date: July 2008
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm I (combination chemotherapy)
Patients receive calaspargase pegol together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo radiation therapy to the head. Treatment may continue for up to 4 years.
Drug: calaspargase pegol
Given IV
Other Names:
  • EZN-2285
  • Oncaspar-IV
  • SC-PEG E. coli L-asparaginase
  • succinimidyl carbonate monomethoxypolyethylene glycol E. coli L-asparaginase
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cytarabine
Given IV, IT, PO, or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: prednisone
Given IV or PO
Other Names:
  • DeCortin
  • Deltra
Drug: methotrexate
Given IV, IT, or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: mercaptopurine tablet
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: dexamethasone
Given PO or IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: thioguanine
Given PO
Other Name: 6-TG
Drug: pegaspargase
Given IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Radiation: radiation therapy
Some patients undergo RT
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies
Active Comparator: Arm II (combination chemotherapy)
Patients receive pegaspargase together with combination chemotherapy. Patients receive chemotherapy PO, IV, SC, and IT. Some patients also undergo RT to the head. Treatment may continue for up to 4 years.
Drug: daunorubicin hydrochloride
Given IV
Other Names:
  • Cerubidin
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057
Drug: doxorubicin hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF
Drug: cytarabine
Given IV, IT, PO, or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside
Drug: prednisone
Given IV or PO
Other Names:
  • DeCortin
  • Deltra
Drug: methotrexate
Given IV, IT, or PO
Other Names:
  • amethopterin
  • Folex
  • methylaminopterin
  • Mexate
  • MTX
Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
Drug: mercaptopurine tablet
Given PO
Other Names:
  • 6-mercaptopurine
  • 6-MP
  • Leukerin
  • MP
Drug: dexamethasone
Given PO or IV
Other Names:
  • Aeroseb-Dex
  • Decaderm
  • Decadron
  • DM
  • DXM
Drug: thioguanine
Given PO
Other Name: 6-TG
Drug: pegaspargase
Given IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase
Drug: vincristine sulfate
Given IV
Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
Radiation: radiation therapy
Some patients undergo RT
Other Names:
  • irradiation
  • radiotherapy
  • therapy, radiation
Other: laboratory biomarker analysis
Correlative studies
Other: pharmacological study
Correlative studies
Other Name: pharmacological studies

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   2 Years to 30 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be eligible for and enrolled on AALL08B1 or the successor classification study
  • Patients must have newly diagnosed high-risk B lymphoblastic leukemia (World Health Organization [WHO] 2008 classification) (also termed B-precursor acute lymphoblastic leukemia)
  • White blood cell (WBC) >= 50,000/μL for patients age 1-9 OR any WBC count for patients age 10-30 or for patients treated with prior steroids
  • Patients shall have had no prior cytotoxic chemotherapy with the exception of steroids and intrathecal cytarabine; intrathecal chemotherapy with cytarabine is allowed prior to registration for patient convenience; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; (Note: the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment) systemic chemotherapy must begin within 72 hours of this intrathecal therapy
  • Patients receiving prior steroid therapy are eligible for this study; the dose and duration of previous steroid therapy should be carefully documented
  • Pregnancy tests with a negative result must be obtained in all post-menarchal females
  • Lactating females must agree that they will not breastfeed a child while on this study

Exclusion Criteria:

  • Patients with Down syndrome are excluded from this study
  • Patients with testicular leukemia at diagnosis are excluded from this study
  • Pregnant female patients are excluded from this study
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00671034

  Show 25 Study Locations
Sponsors and Collaborators
Children's Oncology Group
Investigators
Principal Investigator: Anne Angiolillo, MD Children's Oncology Group
  More Information

No publications provided

Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00671034     History of Changes
Other Study ID Numbers: AALL07P4, NCI-2009-00317, COG-AALL07P4, CDR0000594340, AALL07P4, AALL07P4, U10CA098543
Study First Received: May 1, 2008
Last Updated: August 20, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Leukemia
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Cytarabine
Methotrexate
6-Mercaptopurine
Liposomal doxorubicin
Pegaspargase
Dexamethasone
Doxorubicin
Vincristine
Asparaginase
Daunorubicin
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 22, 2014