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Trial record 21 of 88 for:    "Acute Lymphoblastic Leukemia, Childhood" | "Antineoplastic Agents, Hormonal"

Pegaspargase and Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia (Closed to Accrual 4-22-2011)

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ClinicalTrials.gov Identifier: NCT00866307
Recruitment Status : Completed
First Posted : March 20, 2009
Results First Posted : December 7, 2016
Last Update Posted : March 15, 2017
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Children's Oncology Group

Tracking Information
First Submitted Date  ICMJE March 19, 2009
First Posted Date  ICMJE March 20, 2009
Results First Submitted Date  ICMJE August 1, 2016
Results First Posted Date  ICMJE December 7, 2016
Last Update Posted Date March 15, 2017
Study Start Date  ICMJE February 2009
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 13, 2016)
  • AALL08P1 Safety Outcome [ Time Frame: Consolidation through Delayed Intensification ]
    Percentage of Group B (High Risk-High) patients taking less than 49 weeks from day 1 of consolidation to day 1 of maintenance therapy. Only Group B analyzed since this is prespecified in protocol.
  • AALL08P1 Feasibility Outcome [ Time Frame: Consolidation through Delayed Intensification ]
    Percentage of Group B (High Risk-High) patients that tolerate at least 8 of the 12-14 total doses of pegaspargase during Consolidation, Interim Maintenance, and Delayed Intensification periods. Only Grp B analyzed since this is prespecified in protocol.
Original Primary Outcome Measures  ICMJE
 (submitted: March 19, 2009)
Feasibility and safety of intensified pegaspargase therapy
Change History Complete list of historical versions of study NCT00866307 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pegaspargase and Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia (Closed to Accrual 4-22-2011)
Official Title  ICMJE Intensified PEG-Asparaginase in High Risk Acute Lymphoblastic Leukemia (ALL): A Pilot Study
Brief Summary This pilot clinical trial studies the side effects of pegaspargase when given together with combination chemotherapy in treating patients with newly diagnosed high-risk acute lymphoblastic leukemia. Pegaspargase may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) together with pegaspargase may kill more cancer cells.
Detailed Description

PRIMARY OBJECTIVES:

I. To demonstrate that biweekly intravenous (IV) pegaspargase beginning with Consolidation and ending with completion of delayed intensification (DI) in combination with hemi-augmented BFM therapy (hABFM) is feasible and safe in children with high risk (HR) acute lymphoblastic leukemia (ALL).

OUTLINE: Patients are stratified according to risk assignment (high-risk [HR]-average [day 29 minimal residual disease (MRD) < 0.01%] vs HR-high [MRD >= 0.01%, presence of central nervous system [CNS]3 leukemia, testicular disease, myeloid/mixed lineage leukemia [MLL] rearrangement, hypodiploidy, or steroid therapy within the past month]). Patients are assigned to 1 of 2 treatment groups.*

(Note: *Amendment 2 [4-22-2011] requires changes in the regimens. See the changes below, after Maintenance therapy.)

INDUCTION THERAPY: All patients receive cytarabine intrathecally (IT) on day 1; vincristine sulfate IV on days 1, 8, 15, and 22; prednisone IV or orally (PO) twice daily (BID) on days 1-28; daunorubicin hydrochloride IV over 15 minutes on days 1, 8, 15, and 22; methotrexate IT on days 8 and 29*; and pegaspargase IV over 1-2 hours on day 4.

(Note: *Patients with CNS3 disease [white blood cells [(WBC)] >= 5/uL and positive for blasts on cytospin] also receive methotrexate IT on days 15 and 22.)

CONSOLIDATION THERAPY (begins on day 36 of induction therapy):

GROUP A (HR-AVERAGE): Patients receive cyclophosphamide IV over 1 hour on days 1 and 29; cytarabine IV over 15 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO once daily (QD) on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43, and 50; methotrexate IT on days 1, 8, 15*, and 22*; and pegaspargase IV over 1-2 hours on days 15 and 43.

GROUP B (HR-HIGH): Patients receive cyclophosphamide, cytarabine, mercaptopurine, vincristine sulfate, and methotrexate as in Group A. Beginning on day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks. Patients with CNS3 disease undergo cranial radiotherapy QD for 10 days and patients with testicular disease undergo testicular radiotherapy QD for 12 days, beginning on day 1 of consolidation.

(Note: *Patients with CNS3 disease [WBC >= 5/uL and positive for blasts on cytospin] do not receive methotrexate IT on days 15 and 22.)

Interim maintenance (IM) therapy (begins on day 57 of consolidation):

GROUP A: Patients receive vincristine sulfate IV on days 1, 11, 21, 31, and 41; methotrexate IV over 10-15 minutes on days 1, 11, 21, 31, and 41; methotrexate IT on days 1 and 31; and pegaspargase IV over 1-2 hours on days 2 and 22.

GROUP B: Patients receive vincristine sulfate and methotrexate as in Group A. Beginning on day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks.

DI therapy (begins on day 57 of IM):

GROUP A: Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 15 minutes on days 1, 8, and 15; cyclophosphamide IV over 1 hour on day 29; cytarabine IV over 15 minutes or SC on days 29-32 and 36-39; thioguanine PO on days 29-42; methotrexate IT on days 1, 29, and 36; and pegaspargase IV over 1-2 hours on days 4 and 43.

GROUP B: Patients receive vincristine sulfate, dexamethasone, doxorubicin hydrochloride, cyclophosphamide, cytarabine, thioguanine, and methotrexate as in Group A. Beginning on day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks.

MAINTENANCE THERAPY (MT; begins on day 57 of DI): All patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO on days 1-84; methotrexate IT on day 1; and methotrexate PO BID on days 8, 15, 22, 29*, 36, 43, 50, 57, 64, 71, and 78.

In both groups, MT repeats every 12 weeks until total duration of therapy is 2 years from the start of IM for female patients and 3 years from the start of IM for male patients. Patients in Group B who did not undergo radiotherapy to the brain during consolidation therapy undergo prophylactic cranial radiotherapy (CR) daily for 8 days.

([Note: *Patients in Group A also receive methotrexate IT on day 29 of courses 1-4 [no oral methotrexate]).

REVISED MT (RMT): The regimen is the same as standard MT, but 2 of the doses of IT methotrexate are omitted (day 29 of courses 3 and 4).

Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • B-cell Adult Acute Lymphoblastic Leukemia
  • B-cell Childhood Acute Lymphoblastic Leukemia
  • Untreated Adult Acute Lymphoblastic Leukemia
  • Untreated Childhood Acute Lymphoblastic Leukemia
Intervention  ICMJE
  • Drug: pegaspargase
    Given IV
    Other Names:
    • L-asparaginase with polyethylene glycol
    • Oncaspar
    • PEG-ASP
    • PEG-L-asparaginase
  • Drug: cytarabine
    Given IT and IV or SC
    Other Names:
    • ARA-C
    • arabinofuranosylcytosine
    • arabinosylcytosine
    • Cytosar-U
    • cytosine arabinoside
  • Drug: vincristine sulfate
    Given IV
    Other Names:
    • leurocristine sulfate
    • VCR
    • Vincasar PFS
  • Drug: doxorubicin hydrochloride
    Given IV
    Other Names:
    • ADM
    • ADR
    • Adria
  • Drug: cyclophosphamide
    Given IV
    Other Names:
    • CPM
    • CTX
    • Cytoxan
    • Endoxan
    • Endoxana
  • Drug: prednisone
    Given IV or PO
    Other Names:
    • DeCortin
    • Deltra
  • Drug: dexamethasone
    Given IV
    Other Names:
    • Aeroseb-Dex
    • Decaderm
    • Decadron
    • DM
    • DXM
  • Drug: methotrexate
    Given IT and PO
    Other Names:
    • amethopterin
    • Folex
    • methylaminopterin
    • Mexate
    • MTX
  • Drug: daunorubicin hydrochloride
    Given IV
    Other Names:
    • Cerubidin
    • Cerubidine
    • daunomycin hydrochloride
    • daunorubicin
    • RP-13057
  • Drug: mercaptopurine
    Given PO
    Other Names:
    • 6-mercaptopurine
    • 6-MP
    • Leukerin
    • MP
  • Drug: thioguanine
    Given PO
    Other Name: 6-TG
  • Radiation: prophylactic cranial irradiation
    Undergo radiation
    Other Name: PCI
  • Other: laboratory biomarker analysis
    Correlative studies
Study Arms  ICMJE
  • Experimental: High Risk - Average (Day 29 MRD < 0.01%)
    Cyclophosphamide IV days 1 & 29; cytarabine IV subcutaneously (SC) days 1-4, 8-11, 29-32, & 36-39; mercaptopurine PO once daily (QD) days 1-14 & 29-42; vincristine sulfate IV days 15, 22, 43, & 50; methotrexate IT days 1, 8, 15, & 22; & pegaspargase IV days 15 & 43. Int. Maint.: Vincristine sulfate IV days 1, 11, 21, 31, & 41; methotrexate IV days 1, 11, 21, 31, & 41; methotrexate IT days 1 & 31; and pegaspargase IV days 2 & 22. Delayed Intensification: Vincristine sulfate IV days 1, 8, 15, 43, & 50; dexamethasone IV or PO days 1-7 & 15-21; doxorubicin hydrochloride IV days 1, 8, & 15; cyclophosphamide IV day 29; cytarabine IV or SC days 29-32 & 36-39; thioguanine PO days 29-42; methotrexate IT days 1, 29, & 36; and pegaspargase IV days 4 & 43. Maint. begins day 57 of DI: Vincristine sulfate IV days 1, 29, & 57; prednisone PO days 1-5, 29-33, & 57-61; mercaptopurine PO days 1-84; methotrexate IT day 1; and methotrexate PO days 8, 15, 22, 29*, 36, 43, 50, 57, 64, 71, & 78.
    Interventions:
    • Drug: pegaspargase
    • Drug: cytarabine
    • Drug: vincristine sulfate
    • Drug: doxorubicin hydrochloride
    • Drug: cyclophosphamide
    • Drug: prednisone
    • Drug: dexamethasone
    • Drug: methotrexate
    • Drug: daunorubicin hydrochloride
    • Drug: mercaptopurine
    • Drug: thioguanine
    • Radiation: prophylactic cranial irradiation
    • Other: laboratory biomarker analysis
  • Experimental: High Risk - High (Day 29 MRD ≥ 0.01%) or other factors
    Cyclophosphamide, cytarabine, mercaptopurine, vincristine sulfate, and methotrexate as in group A. Beginning on day 1, pegaspargase IV every 2 weeks. Patients with CNS3 disease undergo cranial radiotherapy QD for 10 days and patients with testicular disease undergo testicular radiotherapy QD for 12 days, beginning on day 1 of consolidation. Interim Maintenance: Patients receive vincristine sulfate and methotrexate as in group A. Beginning on day 1, pegaspargase IV every 2 weeks. Delayed Intensification: Vincristine sulfate, dexamethasone, doxorubicin hydrochloride, cyclophosphamide, cytarabine, thioguanine, and methotrexate as in group A. Beginning on day 1, pegaspargase IV over 1-2 hours every 2 weeks. Maint. begins day 57 of DI: Vincristine sulfate IV days 1, 29, & 57; prednisone PO days 1-5, 29-33, & 57-61; mercaptopurine PO days 1-84; methotrexate IT day 1; and methotrexate PO days 8, 15, 22, 29*, 36, 43, 50, 57, 64, 71, & 78.
    Interventions:
    • Drug: pegaspargase
    • Drug: cytarabine
    • Drug: vincristine sulfate
    • Drug: doxorubicin hydrochloride
    • Drug: cyclophosphamide
    • Drug: prednisone
    • Drug: dexamethasone
    • Drug: methotrexate
    • Drug: daunorubicin hydrochloride
    • Drug: mercaptopurine
    • Drug: thioguanine
    • Radiation: prophylactic cranial irradiation
    • Other: laboratory biomarker analysis
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 13, 2016)
104
Original Estimated Enrollment  ICMJE
 (submitted: March 19, 2009)
165
Actual Study Completion Date  ICMJE June 2014
Actual Primary Completion Date June 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients must be eligible for and enrolled on AALL03B1 or the successor classification study
  • Patients must have newly diagnosed high-risk B-precursor acute lymphoblastic leukemia (ALL)
  • WBC criteria

    • Age 1.00-9.99 years: WBC >= 50,000/uL
    • Age 10.00 - 30.99 years: Any WBC
    • Prior steroid therapy: Any WBC
    • Patients with testicular leukemia: Any WBC
  • 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; 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 study; the dose and duration of previous steroid therapy should be carefully documented
  • All patients and/or their parents or legal guardians must sign a written informed consent
  • All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:

  • Pregnant female patients are ineligible; pregnancy tests with a negative result must be obtained in all post-menarchal females; males and females of reproductive potential may not participate unless they have agreed to use an effective contraceptive method; lactating females must agree that they will not breastfeed a child while on this study
  • Patients with Down syndrome (DS) are ineligible since excessive toxicities and death have been noted for those enrolled on AALL0232 receiving the prednisone/Capizzi methotrexate (PC) arm of treatment, which is the backbone regimen for the current study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 30 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   Canada,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00866307
Other Study ID Numbers  ICMJE AALL08P1
NCI-2009-01169 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
COG-AALL08P1 ( Other Identifier: Children's Oncology Group )
CDR0000636174 ( Other Identifier: ClinicalTrials.gov )
AALL08P1 ( Other Identifier: Children's Oncology Group )
AALL08P1 ( Other Identifier: CTEP )
U10CA098543 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Children's Oncology Group
Study Sponsor  ICMJE Children's Oncology Group
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: ZoAnn Dreyer, MD Children's Oncology Group
PRS Account Children's Oncology Group
Verification Date February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP