Chemotherapy-induced Neutropenia
Conditions
Keywords
Breast Cancer Supportive Care Neutropenia
Brief summary
Determination of the effect of balugrastim on the duration and severity of severe neutropenia.
Interventions
BIOLOGICALBalugrastim
Balugrastim (Recombinant Human Albumin-Human Granulocyte Colony Stimulating Factor) will be administered per dose and schedule specified in the arm description.
DRUGPegfilgrastim
Pegfilgrastim will be administered per dose and schedule specified in the arm description.
The chemotherapy regimen consisting of doxorubicin 60 mg/square meter (m\^2) and docetaxel 75 mg/m\^2 will be administered sequentially by intravenous (IV) infusion on Day 1 of treatment for up to four 21-day cycles.
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Breast cancer participants scheduled to receive the AT regimen (doxorubicin/ docetaxel).
Exclusion criteria
* Participants may have received no more than 1 prior chemotherapy regimen (including adjuvant therapy if given within the last 12 months).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Severe Neutropenia in Cycle 1 | Cycle 1 (cycle length = 21 days) | Severe neutropenia was defined as Grade 4 neutropenia (absolute neutrophil count \[ANC\] \<0.5 x 10\^9/liter \[L\]). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10\^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10\^9/L within the cycle. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Febrile Neutropenia | Cycles 1 to 4 (each cycle length = 21 days) | Febrile neutropenia was defined as an imputed or observed ANC \<0.5 x 10\^9/L and oral temperature ≥38.2 degrees celsius (°C) occurring on the same day. Number of participants with febrile neutropenia over all cycles (Cycles 1 to 4) has been reported. |
| Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycles 2, 3, and 4 (each cycle length = 21 days) | Severe neutropenia was defined as Grade 4 neutropenia (ANC \<0.5 x 10\^9/L). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10\^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10\^9/L within the cycle. |
| Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycles 1, 2, 3, and 4 | Time to ANC recovery was defined as the time from the nadir ANC to an ANC ≥1.5 x 10\^9/L and was calculated for participants with ANC \<1.5 x 10\^9/L after the beginning of a chemotherapy cycle. Time to ANC recovery was calculated by cycle as the number of days from the nadir (the lowest ANC during a chemotherapy cycle) until a participant reached an ANC \>1.5 x 10\^9/L. |
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pilot Phase: Balugrastim Low Dose Participants received balugrastim low dose administered by subcutaneous (SC) injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). | 10 |
| Pilot Phase: Balugrastim Medium Dose Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). | 21 |
| Pilot Phase: Balugrastim High Dose Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). | 20 |
| Pilot Phase: Pegfilgrastim Participants received pegfilgrastim 6 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). | 25 |
| Main Phase: Balugrastim Medium Dose Participants received balugrastim medium dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). | 85 |
| Main Phase: Balugrastim High Dose Participants received balugrastim high dose administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). | 84 |
| Main Phase: Pegfilgrastim Participants received pegfilgrastim 6 mg, administered by SC injection once per chemotherapy cycle (approximately 24 hours after chemotherapy administration) for up to 4 cycles (each cycle length = 21 days). | 86 |
| Total | 331 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Main Phase | Adverse Event | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Main Phase | Death | 0 | 0 | 0 | 0 | 2 | 0 | 1 |
| Main Phase | Decision of the investigator | 0 | 0 | 0 | 0 | 0 | 2 | 1 |
| Main Phase | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Main Phase | Participant's personal reason | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Main Phase | Principal investigator resignation | 0 | 0 | 0 | 0 | 2 | 0 | 0 |
| Main Phase | Withdrawal by Subject | 0 | 0 | 0 | 0 | 4 | 2 | 1 |
| Pilot Phase | Adverse Event | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Pilot Phase | Decision of the investigator | 2 | 1 | 0 | 0 | 0 | 0 | 0 |
| Pilot Phase | Disease progression | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Pilot Phase | Participant left the city | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Pilot Phase | Withdrawal by Subject | 0 | 2 | 3 | 2 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Pilot Phase: Balugrastim Low Dose | Pilot Phase: Balugrastim Medium Dose | Pilot Phase: Balugrastim High Dose | Pilot Phase: Pegfilgrastim | Main Phase: Balugrastim Medium Dose | Main Phase: Balugrastim High Dose | Main Phase: Pegfilgrastim | Total |
|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 56.90 years STANDARD_DEVIATION 9.46 | 51.38 years STANDARD_DEVIATION 10.27 | 53.75 years STANDARD_DEVIATION 9.52 | 52.84 years STANDARD_DEVIATION 10.36 | 49.19 years STANDARD_DEVIATION 9.87 | 49.82 years STANDARD_DEVIATION 9.55 | 50.26 years STANDARD_DEVIATION 9.09 | 50.55 years STANDARD_DEVIATION 9.68 |
| Race/Ethnicity, Customized Race Caucasian | 10 Participants | 21 Participants | 20 Participants | 25 Participants | 85 Participants | 84 Participants | 86 Participants | 331 Participants |
| Sex: Female, Male Female | 10 Participants | 21 Participants | 20 Participants | 25 Participants | 85 Participants | 83 Participants | 86 Participants | 330 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 9 / 10 | 102 / 105 | 100 / 104 | 105 / 112 |
| serious Total, serious adverse events | 3 / 10 | 11 / 105 | 9 / 104 | 10 / 112 |
Outcome results
Primary
Duration of Severe Neutropenia in Cycle 1
Severe neutropenia was defined as Grade 4 neutropenia (absolute neutrophil count \[ANC\] \<0.5 x 10\^9/liter \[L\]). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10\^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10\^9/L within the cycle.
Time frame: Cycle 1 (cycle length = 21 days)
Population: mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pilot Phase: Balugrastim Low Dose | Duration of Severe Neutropenia in Cycle 1 | 0.9 days | Standard Deviation 1.37 |
| Pilot Phase: Balugrastim Medium Dose | Duration of Severe Neutropenia in Cycle 1 | 1.6 days | Standard Deviation 1.83 |
| Pilot Phase: Balugrastim High Dose | Duration of Severe Neutropenia in Cycle 1 | 1.1 days | Standard Deviation 1.48 |
| Pilot Phase: Pegfilgrastim | Duration of Severe Neutropenia in Cycle 1 | 0.9 days | Standard Deviation 1.13 |
| Main Phase: Balugrastim Medium Dose | Duration of Severe Neutropenia in Cycle 1 | 1.0 days | Standard Deviation 1.09 |
| Main Phase: Balugrastim High Dose | Duration of Severe Neutropenia in Cycle 1 | 1.3 days | Standard Deviation 1.22 |
| Main Phase: Pegfilgrastim | Duration of Severe Neutropenia in Cycle 1 | 1.2 days | Standard Deviation 1.34 |
Secondary
Duration of Severe Neutropenia in Cycles 2, 3, and 4
Severe neutropenia was defined as Grade 4 neutropenia (ANC \<0.5 x 10\^9/L). The duration of severe neutropenia was calculated by cycle as the number of days from the first day in which the ANC fell below 0.5 x 10\^9/L after beginning a chemotherapy cycle until the participant had an ANC ≥0.5 x 10\^9/L within the cycle.
Time frame: Cycles 2, 3, and 4 (each cycle length = 21 days)
Population: mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified cycle.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Phase: Balugrastim Low Dose | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 3 | 0.5 days | Standard Deviation 1.07 |
| Pilot Phase: Balugrastim Low Dose | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 4 | 0.9 days | Standard Deviation 0.99 |
| Pilot Phase: Balugrastim Low Dose | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 2 | 0.0 days | Standard Deviation 0 |
| Pilot Phase: Balugrastim Medium Dose | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 2 | 0.8 days | Standard Deviation 1.22 |
| Pilot Phase: Balugrastim Medium Dose | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 4 | 0.3 days | Standard Deviation 0.77 |
| Pilot Phase: Balugrastim Medium Dose | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 3 | 0.7 days | Standard Deviation 0.92 |
| Pilot Phase: Balugrastim High Dose | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 4 | 0.1 days | Standard Deviation 0.49 |
| Pilot Phase: Balugrastim High Dose | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 2 | 0.4 days | Standard Deviation 0.68 |
| Pilot Phase: Balugrastim High Dose | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 3 | 0.6 days | Standard Deviation 1.24 |
| Pilot Phase: Pegfilgrastim | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 3 | 0.3 days | Standard Deviation 0.61 |
| Pilot Phase: Pegfilgrastim | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 4 | 0.7 days | Standard Deviation 1.25 |
| Pilot Phase: Pegfilgrastim | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 2 | 0.5 days | Standard Deviation 0.88 |
| Main Phase: Balugrastim Medium Dose | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 3 | 0.4 days | Standard Deviation 0.78 |
| Main Phase: Balugrastim Medium Dose | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 2 | 0.5 days | Standard Deviation 0.8 |
| Main Phase: Balugrastim Medium Dose | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 4 | 0.4 days | Standard Deviation 0.79 |
| Main Phase: Balugrastim High Dose | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 4 | 0.6 days | Standard Deviation 1.06 |
| Main Phase: Balugrastim High Dose | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 3 | 0.5 days | Standard Deviation 1 |
| Main Phase: Balugrastim High Dose | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 2 | 0.4 days | Standard Deviation 0.8 |
| Main Phase: Pegfilgrastim | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 3 | 0.4 days | Standard Deviation 0.71 |
| Main Phase: Pegfilgrastim | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 2 | 0.5 days | Standard Deviation 0.94 |
| Main Phase: Pegfilgrastim | Duration of Severe Neutropenia in Cycles 2, 3, and 4 | Cycle 4 | 0.6 days | Standard Deviation 1.03 |
Secondary
Number of Participants With Febrile Neutropenia
Febrile neutropenia was defined as an imputed or observed ANC \<0.5 x 10\^9/L and oral temperature ≥38.2 degrees celsius (°C) occurring on the same day. Number of participants with febrile neutropenia over all cycles (Cycles 1 to 4) has been reported.
Time frame: Cycles 1 to 4 (each cycle length = 21 days)
Population: mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Pilot Phase: Balugrastim Low Dose | Number of Participants With Febrile Neutropenia | 2 Participants |
| Pilot Phase: Balugrastim Medium Dose | Number of Participants With Febrile Neutropenia | 3 Participants |
| Pilot Phase: Balugrastim High Dose | Number of Participants With Febrile Neutropenia | 2 Participants |
| Pilot Phase: Pegfilgrastim | Number of Participants With Febrile Neutropenia | 2 Participants |
| Main Phase: Balugrastim Medium Dose | Number of Participants With Febrile Neutropenia | 4 Participants |
| Main Phase: Balugrastim High Dose | Number of Participants With Febrile Neutropenia | 5 Participants |
| Main Phase: Pegfilgrastim | Number of Participants With Febrile Neutropenia | 3 Participants |
Secondary
Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4
Time to ANC recovery was defined as the time from the nadir ANC to an ANC ≥1.5 x 10\^9/L and was calculated for participants with ANC \<1.5 x 10\^9/L after the beginning of a chemotherapy cycle. Time to ANC recovery was calculated by cycle as the number of days from the nadir (the lowest ANC during a chemotherapy cycle) until a participant reached an ANC \>1.5 x 10\^9/L.
Time frame: Cycles 1, 2, 3, and 4
Population: mITT population included all participants who were randomized into the study and received at least 1 dose of assigned study drug. Here, 'Overall number of participants analyzed' = participants evaluable for this outcome measure. 'Number analyzed' = participants evaluable at specified cycle.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pilot Phase: Balugrastim Low Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 1 | 3.1 days | Standard Deviation 2.38 |
| Pilot Phase: Balugrastim Low Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 2 | 1.3 days | Standard Deviation 0.58 |
| Pilot Phase: Balugrastim Low Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 4 | 2.9 days | Standard Deviation 1.68 |
| Pilot Phase: Balugrastim Low Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 3 | 2.1 days | Standard Deviation 1.46 |
| Pilot Phase: Balugrastim Medium Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 4 | 1.8 days | Standard Deviation 0.83 |
| Pilot Phase: Balugrastim Medium Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 2 | 2.1 days | Standard Deviation 1.21 |
| Pilot Phase: Balugrastim Medium Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 1 | 2.6 days | Standard Deviation 1.78 |
| Pilot Phase: Balugrastim Medium Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 3 | 2.0 days | Standard Deviation 1 |
| Pilot Phase: Balugrastim High Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 2 | 1.9 days | Standard Deviation 0.79 |
| Pilot Phase: Balugrastim High Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 1 | 2.0 days | Standard Deviation 1.26 |
| Pilot Phase: Balugrastim High Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 3 | 2.2 days | Standard Deviation 1.39 |
| Pilot Phase: Balugrastim High Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 4 | 1.3 days | Standard Deviation 0.49 |
| Pilot Phase: Pegfilgrastim | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 4 | 2.3 days | Standard Deviation 1.49 |
| Pilot Phase: Pegfilgrastim | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 1 | 2.4 days | Standard Deviation 1.59 |
| Pilot Phase: Pegfilgrastim | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 3 | 1.9 days | Standard Deviation 1.06 |
| Pilot Phase: Pegfilgrastim | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 2 | 1.9 days | Standard Deviation 1.2 |
| Main Phase: Balugrastim Medium Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 4 | 1.9 days | Standard Deviation 0.85 |
| Main Phase: Balugrastim Medium Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 3 | 1.9 days | Standard Deviation 1.08 |
| Main Phase: Balugrastim Medium Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 2 | 1.8 days | Standard Deviation 0.8 |
| Main Phase: Balugrastim Medium Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 1 | 2.0 days | Standard Deviation 0.94 |
| Main Phase: Balugrastim High Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 4 | 2.1 days | Standard Deviation 1.16 |
| Main Phase: Balugrastim High Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 2 | 1.8 days | Standard Deviation 1.11 |
| Main Phase: Balugrastim High Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 3 | 2.2 days | Standard Deviation 1.33 |
| Main Phase: Balugrastim High Dose | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 1 | 2.1 days | Standard Deviation 1.03 |
| Main Phase: Pegfilgrastim | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 2 | 2.1 days | Standard Deviation 1.24 |
| Main Phase: Pegfilgrastim | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 1 | 2.6 days | Standard Deviation 1.23 |
| Main Phase: Pegfilgrastim | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 4 | 2.1 days | Standard Deviation 1.27 |
| Main Phase: Pegfilgrastim | Time to Absolute Neutrophil Count (ANC) Recovery in Cycles 1, 2, 3, and 4 | Cycle 3 | 1.8 days | Standard Deviation 0.79 |