continuation were pancytopenia, thrombocytopenia, and increased alanine aminotransferase (each 2%). A total of 87% of patients reported at least 1 Grade 3 or Grade 4 treatment emergent adverse reactions (Table 1).
Table 1: Adverse Reactions Occurringa in at Least 10% of Patients (Chronic Myeloid Leukemia – Chronic Phase)
Number (%) of Patients
(N=108)
Adverse reactions
All reactions
Grade 3 or 4 reactions
Patients with at least 1 commonly occurring adverse reaction
107 (99)
94 (87)
Blood and Lymphatic System Disorders
Thrombocytopenia
80 (74)
72 (67)
Anemia
66 (61)
39 (36)
Neutropenia
54 (50)
49 (45)
Lymphopenia
18 (17)
17 (16)
Bone Marrow Failure
11 (10)
11 (10)
Febrile Neutropenia
11 (10)
11 (10)
Gastrointestinal Disorders
Diarrhea
45 (42)
1 (1)
Nausea
35 (32)
1 (1)
Constipation
16 (15)
0
Abdominal Pain Upper
15 (14)
0
Vomiting
13 (12)
0
General Disorders and Administration Site Conditions
Fatigue
28 (26)
5 (5)
Pyrexia
26 (24)
1 (1)
Asthenia
25 (23)
1 (1)
Edema Peripheral
14 (13)
0
Infusion and injection site related reactions
37 (34)
0
Infections and Infestationsb
50 (46)
12 (11)
Musculoskeletal and Connective Tissue Disorders
Arthralgia
20 (19)
1 (1)
Pain in Extremity
14 (13)
1 (1)
Back Pain
12 (11)
2 (2)
Nervous System Disorders
Headache
20 (19)
1 (1)
Psychiatric Disorders
Insomnia
11 (10)
0
Respiratory, Thoracic and Mediastinal Disorders
Cough
17 (16)
1 (1)
Epistaxis
16 (15)
1 (1)
Skin and Subcutaneous Tissue Disorders
Alopecia
16 (15)
0
Rash
11 (10)
0
a Occurred in the period between the first dose and 30 days after the last dose.
b Infection includes bacterial, viral, fungal, and non-specified.
Serious adverse reactions were reported for 51% of patients. Serious adverse events reported for at least 5% of patients were bone marrow failure and thrombocytopenia (each 10%), and febrile neutropenia (6%). Serious adverse events of infections were reported for 8% of patients.
Deaths occurred while on study in five (5%) patients with CP CML. Two patients died due to cerebral hemorrhage, one due to multi-organ failure, one due to progression of disease, and one from unknown causes.
Accelerated Phase CML
Median total cycles of exposure was 2 (range 1 to 29), and the median total dose delivered during the trials was 70 mg/m2. The median duration of exposure for the 55 patients with accelerated phase CML was 1.9 months (range 0 to 30 months). Of the patients with accelerated phase CML, 86% received 14 days of treatment during cycle 1. By cycles 2 and 3, the percentage of patients receiving 14 days of treatment decreased to 55% and 44% respectively. Of the 40 patients who received at least 2 cycles of treatment, 27 (68%) had at least 1 cycle delay during the trials. The median number of days of cycle delays was greatest for cycle 3 (31 days) and cycle 8 (36 days).
Adverse reactions regardless of investigator att
