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

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ClinicalTrials.gov Identifier: NCT00671034
Recruitment Status : Completed
First Posted : May 2, 2008
Results First Posted : September 6, 2018
Last Update Posted : September 6, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Brief Summary:
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 or disease Intervention/treatment Phase
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: Pegaspargase Drug: DOXOrubicin Hydrochloride Drug: Cytarabine Drug: Prednisone Drug: methotrexate Drug: cyclophosphamide Drug: mercaptopurine tablet Drug: Dexamethasone Drug: thioguanine Drug: DAUNOrubicin Hydrochloride Drug: vincristine sulfate Radiation: radiation therapy Other: laboratory biomarker analysis Other: pharmacological study Not Applicable

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 166 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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)
Study Start Date : July 2008
Actual Primary Completion Date : February 2011


Arm Intervention/treatment
Experimental: Arm I (calaspargase pegol 2100)
Patients receive calaspargase pegol 2100 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 3 1/2 years.
Drug: calaspargase pegol
Given IV
Other Names:
  • EZN-2285
  • SC-PEG2100 E. coli L-asparaginase
  • succinimidyl carbonate monomethoxypolyethylene glycol E. coli L-asparaginase

Drug: DOXOrubicin Hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF

Drug: Cytarabine
Given IV, IT, or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside

Drug: Prednisone
Given IV or PO
Other Names:
  • DeCortin
  • Delta

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
  • Decadron
  • DM
  • DXM

Drug: thioguanine
Given PO
Other Name: 6-TG

Drug: DAUNOrubicin Hydrochloride
Given IV
Other Names:
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057

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

Experimental: Arm II (calaspargase pegol 2500)
Patients receive calaspargase pegol 2500 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 3 1/2 years.
Drug: calaspargase pegol
Given IV
Other Names:
  • EZN-2285
  • SC-PEG2500 E. coli L-asparaginase
  • succinimidyl carbonate monomethoxypolyethylene glycol E. coli L-asparaginase

Drug: DOXOrubicin Hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF

Drug: Cytarabine
Given IV, IT, or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside

Drug: Prednisone
Given IV or PO
Other Names:
  • DeCortin
  • Delta

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
  • Decadron
  • DM
  • DXM

Drug: thioguanine
Given PO
Other Name: 6-TG

Drug: DAUNOrubicin Hydrochloride
Given IV
Other Names:
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057

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 III (pegaspargase 2500)
Patients receive pegaspargase 2500 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 3 1/2 years.
Drug: Pegaspargase
Given IV
Other Names:
  • L-asparaginase with polyethylene glycol
  • Oncaspar
  • PEG-ASP
  • PEG-L-asparaginase

Drug: DOXOrubicin Hydrochloride
Given IV
Other Names:
  • ADM
  • ADR
  • Adria
  • Adriamycin PFS
  • Adriamycin RDF

Drug: Cytarabine
Given IV, IT, or SC
Other Names:
  • ARA-C
  • arabinofuranosylcytosine
  • arabinosylcytosine
  • Cytosar-U
  • cytosine arabinoside

Drug: Prednisone
Given IV or PO
Other Names:
  • DeCortin
  • Delta

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
  • Decadron
  • DM
  • DXM

Drug: thioguanine
Given PO
Other Name: 6-TG

Drug: DAUNOrubicin Hydrochloride
Given IV
Other Names:
  • Cerubidine
  • daunomycin hydrochloride
  • daunorubicin
  • RP-13057

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




Primary Outcome Measures :
  1. Pharmacokinetics (PK) (Half-life of SC-PEG E. Coli L-asparaginase (EZN-2285) Compared to Pegaspargase During Induction and Consolidation Therapy) [ Time Frame: Post Day 29 of Induction and Post Day 22 of Consolidation ]
    Mean half-life of plasma asparaginase during consolidation and Induction; half-life is defined as the time taken for drug concentration to decrease by half.


Secondary Outcome Measures :
  1. Pharmacodynamics (PD) [ Time Frame: Day 29 of consolidation and induction ]
    Plasma Asparaginase Concentration During consolidation and induction.

  2. Percentage of Participants With Minimal Residual Disease (MRD)<0.01% at the End of Induction [ Time Frame: End of induction (Day 29) ]
    Percentage of participants with Negative MRD (MRD<0.01%).

  3. Percentage of Participants With Complete Remission at the End of Induction [ Time Frame: End of induction (Day 29) ]
    Complete Remission (CR) rate; where CR is defined as M1 marrow (< 5% lymphoblasts in the bone marrow)

  4. Percentage of Participants With Event-free Survival (EFS) [ Time Frame: 5 Years ]
    Percentage of participants who were event free. Event Free Probability defined as time from randomization at study entry to first event (induction failure, induction death, relapse, second malignant neoplasm, remission death) or date of last contact for subjects who are event-free.

  5. Asparaginase Level [ Time Frame: Days 4, 15, 22 and 29 of Induction ]
    The proportion of patients with an asparaginase level of at least 0.1 IU/mL and the proportion with at least 0.4 IU/mL on Days 4, 15, 22 and 29 of Induction compared to Oncaspar

  6. Plasma and CSF Concentrations of Asparagine in ug/ml [ Time Frame: 25 Days Post-dose (Day 29) ]
    The plasma and CSF concentrations of asparagine in ug/ml after administration of EZN-2285 compared to Oncaspar.

  7. Immunogenicity [ Time Frame: 25 Days Post-dose (Day 29) ]
    Number of Patients with Positive Immunogenicity tests

  8. Toxicities During Post Induction Intensification Therapy (All Grades) [ Time Frame: Up to 5 years ]
    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.

  9. Relationship Between PK and Presence of Antibodies [ Time Frame: Day 29 of consolidation ]
    Patients with presence of Antibodies.



Information from the National Library of Medicine

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Layout table for eligibility information
Ages Eligible for Study:   2 Years to 30 Years   (Child, Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00671034


  Show 25 Study Locations
Sponsors and Collaborators
Children's Oncology Group
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Anne Angiolillo, MD Children's Oncology Group

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Children's Oncology Group
ClinicalTrials.gov Identifier: NCT00671034     History of Changes
Other Study ID Numbers: AALL07P4
NCI-2009-00317 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
COG-AALL07P4 ( Other Identifier: Children's Oncology Group )
CDR0000594340 ( Other Identifier: Clinical Trials.gov )
AALL07P4 ( Other Identifier: Children's Oncology Group )
AALL07P4 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
First Posted: May 2, 2008    Key Record Dates
Results First Posted: September 6, 2018
Last Update Posted: September 6, 2018
Last Verified: September 2018

Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Prednisone
Cyclophosphamide
Doxorubicin
Methotrexate
Cytarabine
Vincristine
Liposomal doxorubicin
Daunorubicin
Asparaginase
Mercaptopurine
Pegaspargase
Thioguanine
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones