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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT00866307




Registration number
NCT00866307
Ethics application status
Date submitted
19/03/2009
Date registered
19/03/2009
Date last updated
7/02/2017

Titles & IDs
Public title
Pegaspargase and Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia (Closed to Accrual 4-22-2011)
Scientific title
Intensified PEG-Asparaginase in High Risk Acute Lymphoblastic Leukemia (ALL): A Pilot Study
Secondary ID [1] 0 0
NCI-2009-01169
Secondary ID [2] 0 0
AALL08P1
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
B-cell Adult Acute Lymphoblastic Leukemia 0 0
B-cell Childhood Acute Lymphoblastic Leukemia 0 0
Untreated Adult Acute Lymphoblastic Leukemia 0 0
Untreated Childhood Acute Lymphoblastic Leukemia 0 0
B-cell Adult Acute Lymphoblastic Leukemia 0 0
B-cell Childhood Acute Lymphoblastic Leukemia 0 0
Untreated Adult Acute Lymphoblastic Leukemia 0 0
Untreated Childhood Acute Lymphoblastic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - pegaspargase
Treatment: Drugs - cytarabine
Treatment: Drugs - vincristine sulfate
Treatment: Drugs - doxorubicin hydrochloride
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - prednisone
Treatment: Drugs - dexamethasone
Treatment: Drugs - methotrexate
Treatment: Drugs - daunorubicin hydrochloride
Treatment: Drugs - mercaptopurine
Treatment: Drugs - thioguanine
Treatment: Other - prophylactic cranial irradiation
Other interventions - laboratory biomarker analysis
Treatment: Drugs - pegaspargase
Treatment: Drugs - cytarabine
Treatment: Drugs - vincristine sulfate
Treatment: Drugs - doxorubicin hydrochloride
Treatment: Drugs - cyclophosphamide
Treatment: Drugs - prednisone
Treatment: Drugs - dexamethasone
Treatment: Drugs - methotrexate
Treatment: Drugs - daunorubicin hydrochloride
Treatment: Drugs - mercaptopurine
Treatment: Drugs - thioguanine
Treatment: Other - prophylactic cranial irradiation
Other interventions - laboratory biomarker analysis

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.

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.

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.

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.


Treatment: Drugs: pegaspargase
Given IV

Treatment: Drugs: cytarabine
Given IT and IV or SC

Treatment: Drugs: vincristine sulfate
Given IV

Treatment: Drugs: doxorubicin hydrochloride
Given IV

Treatment: Drugs: cyclophosphamide
Given IV

Treatment: Drugs: prednisone
Given IV or PO

Treatment: Drugs: dexamethasone
Given IV

Treatment: Drugs: methotrexate
Given IT and PO

Treatment: Drugs: daunorubicin hydrochloride
Given IV

Treatment: Drugs: mercaptopurine
Given PO

Treatment: Drugs: thioguanine
Given PO

Treatment: Other: prophylactic cranial irradiation
Undergo radiation

Other interventions: laboratory biomarker analysis
Correlative studies

Treatment: Drugs: pegaspargase
Given IV

Treatment: Drugs: cytarabine
Given IT and IV or SC

Treatment: Drugs: vincristine sulfate
Given IV

Treatment: Drugs: doxorubicin hydrochloride
Given IV

Treatment: Drugs: cyclophosphamide
Given IV

Treatment: Drugs: prednisone
Given IV or PO

Treatment: Drugs: dexamethasone
Given IV

Treatment: Drugs: methotrexate
Given IT and PO

Treatment: Drugs: daunorubicin hydrochloride
Given IV

Treatment: Drugs: mercaptopurine
Given PO

Treatment: Drugs: thioguanine
Given PO

Treatment: Other: prophylactic cranial irradiation
Undergo radiation

Other interventions: laboratory biomarker analysis
Correlative studies

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Treatment: Other
Intervention code [3] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
AALL08P1 Safety Outcome - 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.
Timepoint [1] 0 0
Consolidation through Delayed Intensification
Primary outcome [2] 0 0
AALL08P1 Feasibility Outcome - 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.
Timepoint [2] 0 0
Consolidation through Delayed Intensification
Primary outcome [3] 0 0
AALL08P1 Safety Outcome - 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.
Timepoint [3] 0 0
Consolidation through Delayed Intensification
Primary outcome [4] 0 0
AALL08P1 Feasibility Outcome - 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.
Timepoint [4] 0 0
Consolidation through Delayed Intensification

Eligibility
Key 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
Minimum age
1 Year
Maximum age
30 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 0 0
Princess Margaret Hospital for Children - Perth
Recruitment postcode(s) [1] 0 0
6008 - Perth
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Georgia
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Oregon
Country [11] 0 0
United States of America
State/province [11] 0 0
Pennsylvania
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Other
Name
Children's Oncology Group
Address
Country
Other collaborator category [1] 0 0
Government body
Name [1] 0 0
National Cancer Institute (NCI)
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Government body
Name [2] 0 0
National Cancer Institute (NCI)
Address [2] 0 0
Country [2] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT00866307
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
ZoAnn Dreyer, MD
Address 0 0
Children's Oncology Group
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications