plasma can occur. eva luate bilirubin and transaminases at leastweekly, during cycles of treatment that include ASPARLAS through at least 6 weeks after the last dose ofASPARLAS. In the event of serious liver toxicity, discontinue treatment with ASPARLAS and providesupportive care [see Dosage and Administration (2.2), Contraindications (4), Adverse Reactions (6.1)].
6 ADVERSE REACTIONS
The following clinically significant adverse reactions are described in greater detail in other sectionsof the labeling:
• Hypersensitivity [see Warnings and Precautions (5.1)].
• Pancreatic Toxicity [see Warnings and Precautions (5.2)].
• Thrombosis [see Warnings and Precautions (5.3)].
• Hemorrhage [see Warnings and Precautions (5.4)].
• Hepatotoxicity [see Warnings and Precautions (5.5)].
6.1 Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction ratesobserved in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of anotherdrug and may not reflect the rates observed in practice.
The safety of ASPARLAS was investigated in Study DFCI 11-001, an open-label, randomized,active-controlled multicenter clinical trial that treated 237 children and adolescents with newly-diagnosedALL or lymphoblastic lymphoma, with ASPARLAS 2,500 U/m2 (n=118) or pegaspargase 2,500 U/m2(n=119) as part of a Dana Farber Cancer Institute (DFCI) ALL Consortium backbone therapy. The medianage on enrollment was 5 years (range, 1-20) years. The majority of patients were male (62%) and white
(70%). Most patients were considered standard risk (SR, 59%) and had B-cell lineage ALL (87%).
The median number of doses during the study was 11 doses for ASPARLAS (administered everythree weeks) and 16 doses for pegaspargase (administered every two weeks). The median duration ofexposure was 8 months for both ASPARLAS and pegaspargase.
There was 1 fatal adverse reaction (multi-organ failure in the setting of chronic pancreatitis associatedwith a pancreatic pseudocyst).
Table 2 summarizes the incidence of selected Grades ≥3 adverse reactions that occurred in 2 ormore patients receiving ASPARLAS. Because not all grade 1 and 2 adverse reactions were collectedprospectively, only grade 3 and 4 adverse reactions are presented in Table 1.
Table 2: Selected Grades ≥ 3 Adverse Reactions in Patients Receiving ASPARLAS With
Multi-Agent Chemotherapy (Study DFCI 11-001)*
Adverse Reaction†
ASPARLAS
2,500 U/m2
N=118
Pegaspargase
2,500 U/m2
N=119
Grades ≥ 3
n (%)§
Grades ≥ 3
n (%)§
Elevated transaminase 61 (52) 79 (66)
Bilirubin increased 24 (20) 30 (25)
Pancreatitis 21 (18) 29 (24)
Abnormal clotting studies 17 (14) 25 (21)
Diarrhea 10 (9) 6 (5)
Hypersensitivity 9 (8) 8 (7)
Embolic and thrombotic events 9 (8) 10 (8)
Sepsis 6 (5) 7 (6)
Dyspnea 5 (4) 1 (1)
Hemorrhages 5 (4) 5 (4)
Fungal infection 4 (3) 3 (3)
Pneumonia 4 (3) 8 (7)
Arrhythmia 2 (2) 1 (1)
Cardiac failure 2 (2) 1 (1)
* ASPARLAS and pegaspargase were administered as a component of multi-agent chemotherapy regimens.
†Grouped terms: Elevated transaminase: Alanine aminotransferase increased, Aspartate aminotransferaseincreased, Transaminases increased; Bilirubin increased: Bilirubin conjugated increased, Blood bilirubin increased;Pancreatitis: Amylase
