Pegaspargase and Combination Chemotherapy in Treating Younger Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia (Closed to Accrual 4-22-2011)
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 1 |
Detailed Description
PRIMARY OBJECTIVES:
- 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 Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Arm I (HR-average) See Detailed Description. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT and IV or SC
Other Names:
Drug: Dexamethasone
Given IV
Other Names:
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT and PO
Other Names:
Drug: Pegaspargase
Given IV
Other Names:
Drug: Thioguanine
Given PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
Experimental: Arm II (HR-high) See Detailed Description. |
Drug: Cyclophosphamide
Given IV
Other Names:
Drug: Cytarabine
Given IT and IV or SC
Other Names:
Drug: Daunorubicin Hydrochloride
Given IV
Other Names:
Drug: Dexamethasone
Given IV
Other Names:
Drug: Doxorubicin Hydrochloride
Given IV
Other Names:
Other: Laboratory Biomarker Analysis
Correlative studies
Drug: Mercaptopurine
Given PO
Other Names:
Drug: Methotrexate
Given IT and PO
Other Names:
Drug: Pegaspargase
Given IV
Other Names:
Drug: Prednisone
Given IV or PO
Other Names:
Radiation: Prophylactic Cranial Irradiation
Undergo radiation
Other Names:
Drug: Thioguanine
Given PO
Other Names:
Drug: Vincristine Sulfate
Given IV
Other Names:
|
Outcome Measures
Primary Outcome Measures
- AALL08P1 Safety Outcome [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 [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.
Eligibility Criteria
Criteria
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
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Phoenix Childrens Hospital | Phoenix | Arizona | United States | 85016 |
2 | Miller Children's and Women's Hospital Long Beach | Long Beach | California | United States | 90806 |
3 | Children's Hospital Los Angeles | Los Angeles | California | United States | 90027 |
4 | Valley Children's Hospital | Madera | California | United States | 93636 |
5 | Rady Children's Hospital - San Diego | San Diego | California | United States | 92123 |
6 | UCSF Medical Center-Mount Zion | San Francisco | California | United States | 94115 |
7 | UCSF Medical Center-Parnassus | San Francisco | California | United States | 94143 |
8 | Harbor-University of California at Los Angeles Medical Center | Torrance | California | United States | 90502 |
9 | Nemours Children's Clinic-Jacksonville | Jacksonville | Florida | United States | 32207 |
10 | Children's Healthcare of Atlanta - Egleston | Atlanta | Georgia | United States | 30322 |
11 | Advocate Children's Hospital-Oak Lawn | Oak Lawn | Illinois | United States | 60453 |
12 | Saint Vincent Hospital and Health Care Center | Indianapolis | Indiana | United States | 46260 |
13 | University of Kentucky/Markey Cancer Center | Lexington | Kentucky | United States | 40536 |
14 | Norton Children's Hospital | Louisville | Kentucky | United States | 40202 |
15 | C S Mott Children's Hospital | Ann Arbor | Michigan | United States | 48109 |
16 | University of Mississippi Medical Center | Jackson | Mississippi | United States | 39216 |
17 | The Steven and Alexandra Cohen Children's Medical Center of New York | New Hyde Park | New York | United States | 11040 |
18 | UNC Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina | United States | 27599 |
19 | Nationwide Children's Hospital | Columbus | Ohio | United States | 43205 |
20 | Dayton Children's Hospital | Dayton | Ohio | United States | 45404 |
21 | Legacy Emanuel Children's Hospital | Portland | Oregon | United States | 97227 |
22 | Legacy Emanuel Hospital and Health Center | Portland | Oregon | United States | 97227 |
23 | Children's Oncology Group | Philadelphia | Pennsylvania | United States | 19104 |
24 | Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center | Houston | Texas | United States | 77030 |
25 | Methodist Children's Hospital of South Texas | San Antonio | Texas | United States | 78229 |
26 | Royal Children's Hospital | Parkville | Victoria | Australia | 3052 |
27 | Princess Margaret Hospital for Children | Perth | Western Australia | Australia | 6008 |
28 | Children's Hospital of Eastern Ontario | Ottawa | Ontario | Canada | K1H 8L1 |
Sponsors and Collaborators
- Children's Oncology Group
- National Cancer Institute (NCI)
Investigators
- Principal Investigator: ZoAnn E Dreyer, Children's Oncology Group
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AALL08P1
- NCI-2009-01169
- CDR0000636174
- COG-AALL08P1
- AALL08P1
- AALL08P1
- U10CA098413
- U10CA180886
- U10CA180899
- U10CA098543
Study Results
Participant Flow
Recruitment Details | Patients with newly diagnosed high-risk B-precursor acute lymphoblastic leukemia (ALL), no prior cytotoxic chemotherapy besides steroids and intrathecal cytarabine and WBC criteria: Age 1.00-9.99 years: WBC >= 50,000/uL; Age 10.00 - 30.99 years or prior steroid therapy or with testicular leukemia: Any WBC |
---|---|
Pre-assignment Detail | Patients with Day 29 Marrow counts >25% (M3) or pegaspargase contraindication go off therapy before risk stratification. |
Arm/Group Title | Induction | Group A (High Risk-Average) | Group B (High Risk-High) |
---|---|---|---|
Arm/Group Description | All Patients | Patients with day 29 MRD <0.01% and no CNS3, testicular disease, steroid pretreatment, MLL+, or hypodiploidy. Treated with Standard PEG-asparaginase therapy (hABFM) | Patients with day 29 MRD >=0.01% or at least one of: CNS3, Testicular disease, Steroid Pre-treatment, MLL+, or hypodiploidy. Received Intensified PEG-asparaginase therapy |
Period Title: Induction | |||
STARTED | 104 | 0 | 0 |
COMPLETED | 84 | 0 | 0 |
NOT COMPLETED | 20 | 0 | 0 |
Period Title: Induction | |||
STARTED | 0 | 54 | 30 |
COMPLETED | 0 | 45 | 14 |
NOT COMPLETED | 0 | 9 | 16 |
Baseline Characteristics
Arm/Group Title | Induction |
---|---|
Arm/Group Description | All Patients |
Overall Participants | 104 |
Age (Count of Participants) | |
<=18 years |
96
92.3%
|
Between 18 and 65 years |
8
7.7%
|
>=65 years |
0
0%
|
Sex: Female, Male (Count of Participants) | |
Female |
42
40.4%
|
Male |
62
59.6%
|
Ethnicity (NIH/OMB) (Count of Participants) | |
Hispanic or Latino |
37
35.6%
|
Not Hispanic or Latino |
63
60.6%
|
Unknown or Not Reported |
4
3.8%
|
Race (NIH/OMB) (Count of Participants) | |
American Indian or Alaska Native |
0
0%
|
Asian |
6
5.8%
|
Native Hawaiian or Other Pacific Islander |
2
1.9%
|
Black or African American |
7
6.7%
|
White |
68
65.4%
|
More than one race |
0
0%
|
Unknown or Not Reported |
21
20.2%
|
Outcome Measures
Title | AALL08P1 Safety Outcome |
---|---|
Description | 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. |
Time Frame | Consolidation through Delayed Intensification |
Outcome Measure Data
Analysis Population Description |
---|
Patients with High Risk-High (Group B) Acute Lymphoblastic Leukemia (ALL) |
Arm/Group Title | Group B (High Risk-High) |
---|---|
Arm/Group Description | Patients with day 29 MRD >=0.01% or at least one of: CNS3, Testicular disease, Steroid Pre-treatment, MLL+, or hypodiploidy. Received Intensified PEG-asparaginase therapy |
Measure Participants | 30 |
Number (90% Confidence Interval) [percentage of participants] |
50.0
48.1%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Group B (High Risk-High) |
---|---|---|
Comments | Per protocol, percentage of high risk-High patients taking less than 49 weeks from day 1 of consolidation to day 1 of maintenance therapy is compared to a null fixed rate (<=73%). A 90% two-sided Agresti-Coull confidence interval will be constructed and the lower bound examined. Will reject null if lower bound of confidence interval is above 73%. | |
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Percentage |
Estimated Value | 50.0 | |
Confidence Interval |
(2-Sided) 90% 35.6 to 64.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Title | AALL08P1 Feasibility Outcome |
---|---|
Description | 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. |
Time Frame | Consolidation through Delayed Intensification |
Outcome Measure Data
Analysis Population Description |
---|
Patients with High Risk-high Acute Lymphoblastic Leukemia (ALL) |
Arm/Group Title | Group B (High Risk-High) |
---|---|
Arm/Group Description | Patients with day 29 MRD >=0.01% or at least one of: CNS3, Testicular disease, Steroid Pre-treatment, MLL+, or hypodiploidy. Received Intensified PEG-asparaginase therapy |
Measure Participants | 30 |
Number (90% Confidence Interval) [percentage of participants] |
53.3
51.3%
|
Statistical Analysis 1
Statistical Analysis Overview | Comparison Group Selection | Group B (High Risk-High) |
---|---|---|
Comments | Per protocol, percentage receiving at least 8 doses is compared to a null fixed rate (<=42%). A 90% two-sided Agresti-Coull confidence interval will be constructed. Will reject null if lower bound of confidence interval is above 42%. | |
Type of Statistical Test | Superiority or Other (legacy) | |
Comments | ||
Statistical Test of Hypothesis | p-Value | |
Comments | ||
Method | ||
Comments | ||
Method of Estimation | Estimation Parameter | Percentage |
Estimated Value | 53.3 | |
Confidence Interval |
(2-Sided) 90% 38.7 to 67.4 |
|
Parameter Dispersion |
Type: Value: |
|
Estimation Comments |
Adverse Events
Time Frame | ||||||
---|---|---|---|---|---|---|
Adverse Event Reporting Description | ||||||
Arm/Group Title | Induction | Group A (High Risk-Average) | Group B (High Risk-High) | |||
Arm/Group Description | All Patients | Patients with day 29 MRD <0.01% and no CNS3, testicular disease, steroid pretreatment, MLL+, or hypodiploidy. Treated with Standard PEG-asparaginase therapy (hABFM). | Patients with day 29 MRD >=0.01% or at least one of: CNS3, Testicular disease, Steroid Pre-treatment, MLL+, or hypodiploidy. Received Intensified PEG-asparaginase therapy. | |||
All Cause Mortality |
||||||
Induction | Group A (High Risk-Average) | Group B (High Risk-High) | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
Induction | Group A (High Risk-Average) | Group B (High Risk-High) | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 10/104 (9.6%) | 1/54 (1.9%) | 4/30 (13.3%) | |||
Blood and lymphatic system disorders | ||||||
Disseminated intravascular coagulation | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Cardiac disorders | ||||||
Cardiac arrest | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Cardiac disorders - Other, specify | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Gastrointestinal disorders | ||||||
Colitis | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Typhlitis | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
General disorders | ||||||
Multi-organ failure | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Hepatobiliary disorders | ||||||
Hepatic hemorrhage | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Infections and infestations | ||||||
Infections and infestations - Other, specify | 4/104 (3.8%) | 4 | 0/54 (0%) | 0 | 2/30 (6.7%) | 2 |
Investigations | ||||||
Alanine aminotransferase increased | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Blood bilirubin increased | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Fibrinogen decreased | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Investigations - Other, specify | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Platelet count decreased | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Nervous system disorders | ||||||
Depressed level of consciousness | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Dysphasia | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Intracranial hemorrhage | 2/104 (1.9%) | 2 | 0/54 (0%) | 0 | 2/30 (6.7%) | 2 |
Nervous system disorders - Other, specify | 4/104 (3.8%) | 6 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Seizure | 4/104 (3.8%) | 4 | 1/54 (1.9%) | 1 | 1/30 (3.3%) | 1 |
Syncope | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Respiratory, thoracic and mediastinal disorders | ||||||
Bronchopulmonary hemorrhage | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Hypoxia | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Pneumonitis | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Vascular disorders | ||||||
Hypertension | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Hypotension | 3/104 (2.9%) | 3 | 0/54 (0%) | 0 | 2/30 (6.7%) | 2 |
Thromboembolic event | 2/104 (1.9%) | 2 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Other (Not Including Serious) Adverse Events |
||||||
Induction | Group A (High Risk-Average) | Group B (High Risk-High) | ||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 97/104 (93.3%) | 53/54 (98.1%) | 30/30 (100%) | |||
Blood and lymphatic system disorders | ||||||
Anemia | 32/104 (30.8%) | 58 | 18/54 (33.3%) | 35 | 11/30 (36.7%) | 19 |
Blood and lymphatic system disorders - Other, specify | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Disseminated intravascular coagulation | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Febrile neutropenia | 57/104 (54.8%) | 130 | 38/54 (70.4%) | 85 | 18/30 (60%) | 44 |
Cardiac disorders | ||||||
Wolff-Parkinson-White syndrome | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Eye disorders | ||||||
Optic nerve disorder | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Papilledema | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Gastrointestinal disorders | ||||||
Abdominal pain | 11/104 (10.6%) | 12 | 8/54 (14.8%) | 9 | 3/30 (10%) | 3 |
Ascites | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Colitis | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Constipation | 2/104 (1.9%) | 2 | 1/54 (1.9%) | 1 | 1/30 (3.3%) | 1 |
Diarrhea | 3/104 (2.9%) | 3 | 2/54 (3.7%) | 2 | 1/30 (3.3%) | 1 |
Dysphagia | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Lower gastrointestinal hemorrhage | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Malabsorption | 2/104 (1.9%) | 2 | 2/54 (3.7%) | 2 | 0/30 (0%) | 0 |
Mucositis oral | 10/104 (9.6%) | 10 | 6/54 (11.1%) | 6 | 4/30 (13.3%) | 4 |
Nausea | 3/104 (2.9%) | 3 | 2/54 (3.7%) | 2 | 0/30 (0%) | 0 |
Oral pain | 3/104 (2.9%) | 3 | 2/54 (3.7%) | 2 | 1/30 (3.3%) | 1 |
Pancreatic necrosis | 1/104 (1%) | 2 | 1/54 (1.9%) | 2 | 0/30 (0%) | 0 |
Pancreatitis | 7/104 (6.7%) | 9 | 4/54 (7.4%) | 6 | 2/30 (6.7%) | 2 |
Toothache | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Typhlitis | 3/104 (2.9%) | 3 | 3/54 (5.6%) | 3 | 0/30 (0%) | 0 |
Upper gastrointestinal hemorrhage | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Vomiting | 4/104 (3.8%) | 4 | 4/54 (7.4%) | 4 | 0/30 (0%) | 0 |
General disorders | ||||||
Fatigue | 2/104 (1.9%) | 2 | 1/54 (1.9%) | 1 | 1/30 (3.3%) | 1 |
Fever | 5/104 (4.8%) | 5 | 4/54 (7.4%) | 4 | 0/30 (0%) | 0 |
Gait disturbance | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Pain | 4/104 (3.8%) | 4 | 2/54 (3.7%) | 2 | 2/30 (6.7%) | 2 |
Hepatobiliary disorders | ||||||
Hepatobiliary disorders - Other, specify | 2/104 (1.9%) | 2 | 1/54 (1.9%) | 1 | 1/30 (3.3%) | 1 |
Immune system disorders | ||||||
Allergic reaction | 10/104 (9.6%) | 11 | 7/54 (13%) | 8 | 3/30 (10%) | 3 |
Anaphylaxis | 15/104 (14.4%) | 17 | 9/54 (16.7%) | 11 | 5/30 (16.7%) | 5 |
Immune system disorders - Other, specify | 4/104 (3.8%) | 8 | 3/54 (5.6%) | 7 | 1/30 (3.3%) | 1 |
Infections and infestations | ||||||
Abdominal infection | 2/104 (1.9%) | 2 | 2/54 (3.7%) | 2 | 0/30 (0%) | 0 |
Anorectal infection | 2/104 (1.9%) | 2 | 2/54 (3.7%) | 2 | 0/30 (0%) | 0 |
Appendicitis perforated | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Bladder infection | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Bronchial infection | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Catheter related infection | 4/104 (3.8%) | 4 | 2/54 (3.7%) | 2 | 2/30 (6.7%) | 2 |
Enterocolitis infectious | 6/104 (5.8%) | 8 | 6/54 (11.1%) | 8 | 0/30 (0%) | 0 |
Esophageal infection | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Infections and infestations - Other, specify | 62/104 (59.6%) | 155 | 39/54 (72.2%) | 98 | 17/30 (56.7%) | 39 |
Infective myositis | 1/104 (1%) | 2 | 1/54 (1.9%) | 2 | 0/30 (0%) | 0 |
Kidney infection | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Lung infection | 10/104 (9.6%) | 16 | 7/54 (13%) | 11 | 3/30 (10%) | 5 |
Lymph gland infection | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Mucosal infection | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Nail infection | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Otitis media | 2/104 (1.9%) | 2 | 2/54 (3.7%) | 2 | 0/30 (0%) | 0 |
Sepsis | 2/104 (1.9%) | 2 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Sinusitis | 4/104 (3.8%) | 4 | 4/54 (7.4%) | 4 | 0/30 (0%) | 0 |
Skin infection | 5/104 (4.8%) | 6 | 2/54 (3.7%) | 2 | 2/30 (6.7%) | 3 |
Upper respiratory infection | 6/104 (5.8%) | 7 | 3/54 (5.6%) | 4 | 3/30 (10%) | 3 |
Urinary tract infection | 4/104 (3.8%) | 9 | 3/54 (5.6%) | 4 | 1/30 (3.3%) | 5 |
Vaginal infection | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Wound infection | 1/104 (1%) | 4 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Injury, poisoning and procedural complications | ||||||
Intraoperative gastrointestinal injury | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Vascular access complication | 8/104 (7.7%) | 11 | 6/54 (11.1%) | 9 | 1/30 (3.3%) | 1 |
Wound dehiscence | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Investigations | ||||||
Activated partial thromboplastin time prolonged | 2/104 (1.9%) | 3 | 2/54 (3.7%) | 3 | 0/30 (0%) | 0 |
Alanine aminotransferase increased | 47/104 (45.2%) | 100 | 28/54 (51.9%) | 70 | 15/30 (50%) | 25 |
Alkaline phosphatase increased | 4/104 (3.8%) | 4 | 3/54 (5.6%) | 3 | 1/30 (3.3%) | 1 |
Aspartate aminotransferase increased | 23/104 (22.1%) | 30 | 14/54 (25.9%) | 20 | 7/30 (23.3%) | 8 |
Blood bilirubin increased | 19/104 (18.3%) | 29 | 10/54 (18.5%) | 15 | 6/30 (20%) | 11 |
Cholesterol high | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Creatinine increased | 2/104 (1.9%) | 2 | 1/54 (1.9%) | 1 | 1/30 (3.3%) | 1 |
Fibrinogen decreased | 11/104 (10.6%) | 15 | 7/54 (13%) | 11 | 3/30 (10%) | 3 |
GGT increased | 9/104 (8.7%) | 9 | 1/54 (1.9%) | 1 | 6/30 (20%) | 6 |
INR increased | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Investigations - Other, specify | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Lipase increased | 10/104 (9.6%) | 13 | 5/54 (9.3%) | 8 | 3/30 (10%) | 3 |
Lymphocyte count decreased | 2/104 (1.9%) | 4 | 2/54 (3.7%) | 4 | 0/30 (0%) | 0 |
Neutrophil count decreased | 72/104 (69.2%) | 212 | 47/54 (87%) | 144 | 21/30 (70%) | 61 |
Pancreatic enzymes decreased | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Platelet count decreased | 34/104 (32.7%) | 70 | 20/54 (37%) | 37 | 11/30 (36.7%) | 22 |
Serum amylase increased | 5/104 (4.8%) | 6 | 3/54 (5.6%) | 4 | 1/30 (3.3%) | 1 |
Weight gain | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Weight loss | 6/104 (5.8%) | 8 | 4/54 (7.4%) | 5 | 2/30 (6.7%) | 3 |
White blood cell decreased | 37/104 (35.6%) | 102 | 22/54 (40.7%) | 64 | 12/30 (40%) | 33 |
Metabolism and nutrition disorders | ||||||
Anorexia | 7/104 (6.7%) | 8 | 3/54 (5.6%) | 4 | 3/30 (10%) | 3 |
Dehydration | 4/104 (3.8%) | 4 | 3/54 (5.6%) | 3 | 1/30 (3.3%) | 1 |
Glucose intolerance | 5/104 (4.8%) | 6 | 4/54 (7.4%) | 5 | 1/30 (3.3%) | 1 |
Hypercalcemia | 1/104 (1%) | 2 | 1/54 (1.9%) | 2 | 0/30 (0%) | 0 |
Hyperglycemia | 24/104 (23.1%) | 31 | 12/54 (22.2%) | 18 | 8/30 (26.7%) | 9 |
Hyperkalemia | 8/104 (7.7%) | 8 | 4/54 (7.4%) | 4 | 3/30 (10%) | 3 |
Hypermagnesemia | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Hypertriglyceridemia | 3/104 (2.9%) | 3 | 3/54 (5.6%) | 3 | 0/30 (0%) | 0 |
Hyperuricemia | 2/104 (1.9%) | 2 | 1/54 (1.9%) | 1 | 1/30 (3.3%) | 1 |
Hypoalbuminemia | 9/104 (8.7%) | 12 | 3/54 (5.6%) | 3 | 3/30 (10%) | 6 |
Hypocalcemia | 11/104 (10.6%) | 12 | 7/54 (13%) | 8 | 3/30 (10%) | 3 |
Hypokalemia | 12/104 (11.5%) | 16 | 6/54 (11.1%) | 8 | 4/30 (13.3%) | 6 |
Hyponatremia | 20/104 (19.2%) | 24 | 10/54 (18.5%) | 13 | 7/30 (23.3%) | 7 |
Hypophosphatemia | 7/104 (6.7%) | 7 | 1/54 (1.9%) | 1 | 4/30 (13.3%) | 4 |
Iron overload | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Obesity | 2/104 (1.9%) | 2 | 2/54 (3.7%) | 2 | 0/30 (0%) | 0 |
Tumor lysis syndrome | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Musculoskeletal and connective tissue disorders | ||||||
Arthralgia | 2/104 (1.9%) | 2 | 1/54 (1.9%) | 1 | 1/30 (3.3%) | 1 |
Avascular necrosis | 9/104 (8.7%) | 22 | 7/54 (13%) | 19 | 2/30 (6.7%) | 3 |
Back pain | 3/104 (2.9%) | 3 | 2/54 (3.7%) | 2 | 1/30 (3.3%) | 1 |
Joint effusion | 1/104 (1%) | 2 | 1/54 (1.9%) | 2 | 0/30 (0%) | 0 |
Joint range of motion decreased | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Muscle weakness lower limb | 3/104 (2.9%) | 7 | 1/54 (1.9%) | 4 | 1/30 (3.3%) | 1 |
Neck pain | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Pain in extremity | 9/104 (8.7%) | 13 | 5/54 (9.3%) | 6 | 3/30 (10%) | 3 |
Soft tissue necrosis lower limb | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Soft tissue necrosis upper limb | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Nervous system disorders | ||||||
Abducens nerve disorder | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Arachnoiditis | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Ataxia | 2/104 (1.9%) | 3 | 2/54 (3.7%) | 3 | 0/30 (0%) | 0 |
Cerebrospinal fluid leakage | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Cognitive disturbance | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Concentration impairment | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Depressed level of consciousness | 2/104 (1.9%) | 2 | 1/54 (1.9%) | 1 | 1/30 (3.3%) | 1 |
Dizziness | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Dysphasia | 2/104 (1.9%) | 2 | 2/54 (3.7%) | 2 | 0/30 (0%) | 0 |
Encephalopathy | 2/104 (1.9%) | 2 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Headache | 4/104 (3.8%) | 5 | 3/54 (5.6%) | 4 | 1/30 (3.3%) | 1 |
Ischemia cerebrovascular | 2/104 (1.9%) | 2 | 0/54 (0%) | 0 | 2/30 (6.7%) | 2 |
Leukoencephalopathy | 4/104 (3.8%) | 4 | 3/54 (5.6%) | 3 | 1/30 (3.3%) | 1 |
Neuralgia | 2/104 (1.9%) | 4 | 1/54 (1.9%) | 2 | 1/30 (3.3%) | 2 |
Oculomotor nerve disorder | 2/104 (1.9%) | 3 | 1/54 (1.9%) | 2 | 1/30 (3.3%) | 1 |
Peripheral motor neuropathy | 20/104 (19.2%) | 30 | 10/54 (18.5%) | 13 | 9/30 (30%) | 16 |
Peripheral sensory neuropathy | 22/104 (21.2%) | 31 | 13/54 (24.1%) | 16 | 7/30 (23.3%) | 12 |
Seizure | 5/104 (4.8%) | 5 | 4/54 (7.4%) | 4 | 1/30 (3.3%) | 1 |
Syncope | 2/104 (1.9%) | 2 | 1/54 (1.9%) | 1 | 1/30 (3.3%) | 1 |
Tremor | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Psychiatric disorders | ||||||
Agitation | 4/104 (3.8%) | 4 | 2/54 (3.7%) | 2 | 0/30 (0%) | 0 |
Anxiety | 2/104 (1.9%) | 3 | 2/54 (3.7%) | 3 | 0/30 (0%) | 0 |
Confusion | 2/104 (1.9%) | 2 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Depression | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Hallucinations | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Insomnia | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Personality change | 3/104 (2.9%) | 4 | 2/54 (3.7%) | 2 | 1/30 (3.3%) | 2 |
Psychosis | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Suicidal ideation | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Renal and urinary disorders | ||||||
Renal and urinary disorders - Other, specify | 1/104 (1%) | 2 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Urinary tract pain | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Reproductive system and breast disorders | ||||||
Uterine hemorrhage | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders | ||||||
Adult respiratory distress syndrome | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Cough | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Dyspnea | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Hypoxia | 5/104 (4.8%) | 5 | 3/54 (5.6%) | 3 | 0/30 (0%) | 0 |
Pharyngeal mucositis | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Pharyngolaryngeal pain | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 1/30 (3.3%) | 1 |
Pleural effusion | 4/104 (3.8%) | 5 | 2/54 (3.7%) | 2 | 2/30 (6.7%) | 3 |
Pneumonitis | 2/104 (1.9%) | 2 | 2/54 (3.7%) | 2 | 0/30 (0%) | 0 |
Pneumothorax | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Respiratory, thoracic and mediastinal disorders - Other, specify | 1/104 (1%) | 1 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Skin and subcutaneous tissue disorders | ||||||
Skin ulceration | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Urticaria | 1/104 (1%) | 1 | 1/54 (1.9%) | 1 | 0/30 (0%) | 0 |
Vascular disorders | ||||||
Hypertension | 7/104 (6.7%) | 7 | 2/54 (3.7%) | 2 | 4/30 (13.3%) | 4 |
Hypotension | 3/104 (2.9%) | 3 | 2/54 (3.7%) | 2 | 1/30 (3.3%) | 1 |
Thromboembolic event | 3/104 (2.9%) | 3 | 3/54 (5.6%) | 3 | 0/30 (0%) | 0 |
Vascular disorders - Other, specify | 2/104 (1.9%) | 2 | 0/54 (0%) | 0 | 0/30 (0%) | 0 |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Must obtain prior Sponsor approval.
Results Point of Contact
Name/Title | Results Reporting Coordinator |
---|---|
Organization | Children's Oncology Group |
Phone | 626-447-0064 |
resultsreportingcoordinator@childrensoncologygroup.org |
- AALL08P1
- NCI-2009-01169
- CDR0000636174
- COG-AALL08P1
- AALL08P1
- AALL08P1
- U10CA098413
- U10CA180886
- U10CA180899
- U10CA098543