Trial Outcomes & Findings for Chemosensitization With Plerixafor Plus G-CSF in Acute Myeloid Leukemia (NCT NCT00906945)
NCT ID: NCT00906945
Last Updated: 2017-04-04
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
39 participants
Primary outcome timeframe
Completion of Phase I enrollment (17 months)
Results posted on
2017-04-04
Participant Flow
The study opened to participant enrollment on 02/04/2011 and closed to participant enrollment on 08/19/2013.
Participant milestones
| Measure |
Dose Level 1
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 240 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 2
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 320 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 3
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 420 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 4
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 560 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 5
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 750 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
MTD - Phase II
* G-CSF MTD determined in Phase 1 SQ on Days 1-8
* Plerixafor MTD determined in Phase 1 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
|---|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
3
|
3
|
7
|
7
|
16
|
|
Overall Study
COMPLETED
|
3
|
3
|
3
|
6
|
6
|
14
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
1
|
1
|
2
|
Reasons for withdrawal
| Measure |
Dose Level 1
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 240 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 2
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 320 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 3
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 420 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 4
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 560 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 5
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 750 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
MTD - Phase II
* G-CSF MTD determined in Phase 1 SQ on Days 1-8
* Plerixafor MTD determined in Phase 1 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
|---|---|---|---|---|---|---|
|
Overall Study
Found to be not eligible
|
0
|
0
|
0
|
1
|
1
|
1
|
|
Overall Study
Physician Decision
|
0
|
0
|
0
|
0
|
0
|
1
|
Baseline Characteristics
Chemosensitization With Plerixafor Plus G-CSF in Acute Myeloid Leukemia
Baseline characteristics by cohort
| Measure |
Dose Level 1
n=3 Participants
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 240 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 2
n=3 Participants
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 320 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 3
n=3 Participants
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 420 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 4
n=6 Participants
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 560 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 5 (Includes MTD-Phase II)
n=20 Participants
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 750 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Total
n=35 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|---|
|
Age, Continuous
|
63 years
n=5 Participants
|
47 years
n=7 Participants
|
64 years
n=5 Participants
|
54 years
n=4 Participants
|
56 years
n=21 Participants
|
56 years
n=8 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
4 Participants
n=4 Participants
|
8 Participants
n=21 Participants
|
17 Participants
n=8 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
2 Participants
n=4 Participants
|
12 Participants
n=21 Participants
|
18 Participants
n=8 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
3 participants
n=7 Participants
|
3 participants
n=5 Participants
|
6 participants
n=4 Participants
|
20 participants
n=21 Participants
|
35 participants
n=8 Participants
|
PRIMARY outcome
Timeframe: Completion of Phase I enrollment (17 months)Population: Number of participants analyzed is the number of participants enrolled in the Phase I portion of the study.
Outcome measures
| Measure |
Phase I (Includes Levels 1-5)
n=21 Participants
|
Grade 2
|
Grade 3
|
Grade 4
|
Grade 5
|
|---|---|---|---|---|---|
|
Phase I: Maximum Tolerated Dose of Plerixafor Plus G-CSF When Combined With MEC
|
750 mcg/kg/day
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 45 daysPopulation: Only patients enrolled in Phase 2 portion were analyzed for this outcome measure.
* Morphologic complete remission (CR): Defined as morphologic leukemia-free state, including \<5% blasts in BM aspirate with marrow spicules and a count of \> 200 nucleated cells and no blasts with Auer rods, no persistent extramedullary disease, ANC \> 1,000/mm3, platelet count \> 100,000/mm3. * Morphologic complete remission with incomplete blood count recovery (CRi): Defined as CR with the exception of neutropenia \<1,000/mm3 or thrombocytopenia \<100,000/mm3.
Outcome measures
| Measure |
Phase I (Includes Levels 1-5)
n=20 Participants
|
Grade 2
|
Grade 3
|
Grade 4
|
Grade 5
|
|---|---|---|---|---|---|
|
Phase II: Complete Response Rate (CR+CRi)
|
30 percentage of participants
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 30 days following end of treatmentOutcome measures
| Measure |
Phase I (Includes Levels 1-5)
n=35 Participants
|
Grade 2
n=35 Participants
|
Grade 3
n=35 Participants
|
Grade 4
n=35 Participants
|
Grade 5
n=35 Participants
|
|---|---|---|---|---|---|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Febrile neutropenia
|
0 number of events
|
0 number of events
|
20 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Diarrhea
|
7 number of events
|
6 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Gastroesophageal reflux disease
|
1 number of events
|
5 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Dizziness
|
4 number of events
|
1 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Headache
|
7 number of events
|
6 number of events
|
1 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Paresthesia
|
4 number of events
|
1 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Insomnia
|
5 number of events
|
2 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Proteinuria
|
3 number of events
|
1 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Cough
|
3 number of events
|
2 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Dyspnea
|
3 number of events
|
3 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Pneumonitis
|
1 number of events
|
3 number of events
|
0 number of events
|
0 number of events
|
1 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Rash maculo-papular
|
3 number of events
|
3 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Hypotension
|
4 number of events
|
4 number of events
|
2 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Hypocalcemia
|
2 number of events
|
11 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Hypoalbuminemia
|
3 number of events
|
6 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Anemia
|
0 number of events
|
4 number of events
|
9 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Abdominal pain
|
6 number of events
|
0 number of events
|
1 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Constipation
|
5 number of events
|
2 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Mucositis oral
|
2 number of events
|
3 number of events
|
1 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Nausea
|
21 number of events
|
3 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Vomiting
|
12 number of events
|
0 number of events
|
1 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Chills
|
5 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Edema-limbs
|
5 number of events
|
1 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Fatigue
|
9 number of events
|
2 number of events
|
1 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Fever
|
6 number of events
|
4 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Non-cardiac chest pain
|
1 number of events
|
2 number of events
|
1 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Pain
|
2 number of events
|
2 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Bacteremia
|
0 number of events
|
0 number of events
|
4 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Lung infection
|
0 number of events
|
1 number of events
|
5 number of events
|
0 number of events
|
2 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Sepsis
|
0 number of events
|
0 number of events
|
0 number of events
|
4 number of events
|
4 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Activated partial thromboplastin time prolonged
|
5 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Alanine aminotransferase increased
|
3 number of events
|
0 number of events
|
1 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Alkaline phosphatase increased
|
3 number of events
|
1 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Aspartate aminotransferase increased
|
4 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Blood bilirubin increased
|
2 number of events
|
3 number of events
|
1 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
INR increased
|
7 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Neutrophil count decreased
|
0 number of events
|
0 number of events
|
0 number of events
|
7 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Platelet count decreased
|
0 number of events
|
0 number of events
|
0 number of events
|
15 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
White blood cell count decreased
|
0 number of events
|
0 number of events
|
0 number of events
|
16 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Anorexia
|
4 number of events
|
2 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Hypokalemia
|
5 number of events
|
2 number of events
|
2 number of events
|
2 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Hypomagnesemia
|
7 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Hyponatremia
|
4 number of events
|
0 number of events
|
1 number of events
|
0 number of events
|
0 number of events
|
|
Phase I and Phase II: Safety and Tolerability of Regimen as Measured by Grade and Frequency of Adverse Events Exceeding 10% in Total Frequency
Bone pain
|
4 number of events
|
2 number of events
|
2 number of events
|
0 number of events
|
0 number of events
|
SECONDARY outcome
Timeframe: Up to 62 days after treatmentPopulation: All participants enrolled in the study (both Phase I or Phase II) who had a CR/CRi whose ANC was \>=500/mm\^3 were evaluable for this outcome measure.
-Neutrophil recovery is defined as absolute neutrophil count (ANC) \>= 500/mm\^3
Outcome measures
| Measure |
Phase I (Includes Levels 1-5)
n=9 Participants
|
Grade 2
|
Grade 3
|
Grade 4
|
Grade 5
|
|---|---|---|---|---|---|
|
Time to Hematologic Recovery as Measured by Time to Neutrophil Recovery
|
38 days
Interval 21.0 to 62.0
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 62 days after treatmentPopulation: All participants enrolled in the study (both Phase I or Phase II) who had a CR/CRi whose ANC was \>=1000/mm\^3 were evaluable for this outcome measure.
-Neutrophil recovery is defined as absolute neutrophil count \>= 1000/mm\^3
Outcome measures
| Measure |
Phase I (Includes Levels 1-5)
n=8 Participants
|
Grade 2
|
Grade 3
|
Grade 4
|
Grade 5
|
|---|---|---|---|---|---|
|
Time to Hematologic Recovery as Measured by Time to Neutrophil Recovery
|
40 days
Interval 23.0 to 62.0
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 62 days after treatmentPopulation: All participants enrolled in the study (both Phase I or Phase II) who had CR whose platelets were \>=50,000/mm\^3 were evaluable for this outcome measure.
-Platelet recovery is defined as platelets \>= 50,000/mm\^3
Outcome measures
| Measure |
Phase I (Includes Levels 1-5)
n=9 Participants
|
Grade 2
|
Grade 3
|
Grade 4
|
Grade 5
|
|---|---|---|---|---|---|
|
Time to Hematologic Recovery as Measured by Time to Platelet Recovery
|
32 days
Interval 27.0 to 62.0
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 62 days after treatmentPopulation: All participants enrolled in the study (both Phase I or Phase II) who had a CR whose platelets were \>=100,000/mm\^3 were evaluable for this outcome measure.
-Platelet recovery is defined as platelets \>= 100,000/mm3
Outcome measures
| Measure |
Phase I (Includes Levels 1-5)
n=7 Participants
|
Grade 2
|
Grade 3
|
Grade 4
|
Grade 5
|
|---|---|---|---|---|---|
|
Time to Hematologic Recovery as Measured by Time to Platelet Recovery
|
32 days
Interval 30.0 to 62.0
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 hours after plerixaforPopulation: 31 patients were evaluable for this outcome measure (3 patients were never treated due to being ineligible and 1 patient never treated due to physician decision). The remaining 4 patients did not have usable peripheral blood samples for this outcome measure.
Outcome measures
| Measure |
Phase I (Includes Levels 1-5)
n=31 Participants
|
Grade 2
|
Grade 3
|
Grade 4
|
Grade 5
|
|---|---|---|---|---|---|
|
Characterize the Mobilization of Leukemic Cells With Plerixafor Plus G-CSF as Measured by Fold Change in White Blood Cells
|
4.6 fold change in white blood cells
Standard Deviation 3.6
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 hours after plerixaforPopulation: 31 patients were evaluable for this outcome measure (3 patients were never treated due to being ineligible and 1 patient never treated due to physician decision). The remaining 4 patients did not have usable peripheral blood samples for this outcome measure.
Outcome measures
| Measure |
Phase I (Includes Levels 1-5)
n=31 Participants
|
Grade 2
|
Grade 3
|
Grade 4
|
Grade 5
|
|---|---|---|---|---|---|
|
Characterize the Mobilization of Leukemic Cells With Plerixafor Plus G-CSF as Measured by Fold Change in AML Blast Count
|
9.4 fold change in AML blast count
Standard Deviation 11.6
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 hours after plerixaforPopulation: 29 patients were evaluable for this outcome measure (3 patients were never treated due to being ineligible and 1 patient never treated due to physician decision). The remaining 6 patients did not have usable peripheral blood samples for this outcome measure.
Outcome measures
| Measure |
Phase I (Includes Levels 1-5)
n=29 Participants
|
Grade 2
|
Grade 3
|
Grade 4
|
Grade 5
|
|---|---|---|---|---|---|
|
Characterize the Effects of Plerixafor Plus G-CSF on Fold Change in CXCR4 Clone 1D9 Relative Mean Fluorescent Intensity
|
8.0 fold change in CXCR4 clone 1D9
Standard Deviation 13.2
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 6 hours after plerixaforPopulation: 29 patients were evaluable for this outcome measure (3 patients were never treated due to being ineligible and 1 patient never treated due to physician decision). The remaining 6 patients did not have usable peripheral blood samples for this outcome measure.
Outcome measures
| Measure |
Phase I (Includes Levels 1-5)
n=29 Participants
|
Grade 2
|
Grade 3
|
Grade 4
|
Grade 5
|
|---|---|---|---|---|---|
|
Characterize the Effects of Plerixafor Plus G-CSF on Fold Change in CXCR4 Clone 12G5 Relative Mean Fluorescent Intensity
|
0.9 fold change in CXCR4 clone 1D9
Standard Deviation 0.9
|
—
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: 2 yearsPopulation: Data was not collected for this outcome measure. Progression is very hard to define acute myeloid leukemia and including it as a pre-specified secondary outcome measure in the protocol was an oversight.
Recurrence / morphologic relapse: Defined as reappearance of blasts in the blood or the finding of \> 5% blasts in the BM, not attributable to any other cause. New dysplastic changes are considered a relapse. If there are no blasts in the peripheral blood and 5-19% blasts in the BM, the BM biopsy and aspirate should be repeated in \> 1 week to confirm relapse.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 8 daysPopulation: Data was not collected for this outcome measure. It is not well defined in the literature as when to measure treatment failure. Relapse free survival is a better way to measure response duration (this outcome measure was added to the results).
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Median follow-up was 34.6 monthsOverall survival: Defined as the date of first dose of study drug to the date of death from any cause.
Outcome measures
| Measure |
Phase I (Includes Levels 1-5)
n=35 Participants
|
Grade 2
|
Grade 3
|
Grade 4
|
Grade 5
|
|---|---|---|---|---|---|
|
Overall Survival
|
227 days
Interval 13.0 to 1633.0
|
—
|
—
|
—
|
—
|
POST_HOC outcome
Timeframe: 2 yearsPopulation: All participants enrolled in the study (both Phase I or Phase II) who had a CR/CRi were evaluable for this outcome measure.
Outcome measures
| Measure |
Phase I (Includes Levels 1-5)
n=9 Participants
|
Grade 2
|
Grade 3
|
Grade 4
|
Grade 5
|
|---|---|---|---|---|---|
|
Relapse Free-survival Rate
|
75 percentage of participants
|
—
|
—
|
—
|
—
|
Adverse Events
Dose Level 1
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Dose Level 2
Serious events: 2 serious events
Other events: 3 other events
Deaths: 0 deaths
Dose Level 3
Serious events: 0 serious events
Other events: 3 other events
Deaths: 0 deaths
Dose Level 4
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
Dose Level 5
Serious events: 2 serious events
Other events: 6 other events
Deaths: 0 deaths
MTD - Phase II
Serious events: 2 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Dose Level 1
n=3 participants at risk
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 240 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 2
n=3 participants at risk
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 320 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 3
n=3 participants at risk
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 420 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 4
n=6 participants at risk
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 560 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 5
n=6 participants at risk
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 750 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
MTD - Phase II
n=14 participants at risk
* G-CSF MTD determined in Phase 1 SQ on Days 1-8
* Plerixafor MTD determined in Phase 1 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
|---|---|---|---|---|---|---|
|
Musculoskeletal and connective tissue disorders
Body pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Cardiac disorders
Cardiac troponin increased
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Vascular disorders
Hypotension
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Infections and infestations
Lung infection
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Infections and infestations
Sepsis
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
33.3%
2/6
|
16.7%
1/6
|
7.1%
1/14
|
|
Vascular disorders
Subdural hematoma
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
Other adverse events
| Measure |
Dose Level 1
n=3 participants at risk
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 240 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 2
n=3 participants at risk
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 320 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 3
n=3 participants at risk
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 420 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 4
n=6 participants at risk
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 560 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
Dose Level 5
n=6 participants at risk
* G-CSF 10 mcg/kg SQ on Days 1-8
* Plerixafor 750 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
MTD - Phase II
n=14 participants at risk
* G-CSF MTD determined in Phase 1 SQ on Days 1-8
* Plerixafor MTD determined in Phase 1 mcg/kg/d IV qd
* Mitoxantrone 8 mg/m2/day IV once over 30 minutes daily on days 4-8
* Etoposide 100 mg/m2/day IV once over 60 minutes daily on days 4-8
* Cytarabine 1000 mg/m2/day IV once over 60 minutes daily on days 4-8
|
|---|---|---|---|---|---|---|
|
Gastrointestinal disorders
Abdominal cramping
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Gastrointestinal disorders
Abdominal pain
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
50.0%
3/6
|
33.3%
2/6
|
7.1%
1/14
|
|
Investigations
Activated partial thromboplastin time prolonged
|
0.00%
0/3
|
66.7%
2/3
|
0.00%
0/3
|
16.7%
1/6
|
16.7%
1/6
|
7.1%
1/14
|
|
Renal and urinary disorders
Acute kidney injury
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
7.1%
1/14
|
|
Investigations
Alanine aminotransferase increased
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
16.7%
1/6
|
7.1%
1/14
|
|
Investigations
Alkaline phosphatase increased
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
21.4%
3/14
|
|
Immune system disorders
Allergic reaction
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
14.3%
2/14
|
|
Respiratory, thoracic and mediastinal disorders
Allergic rhinitis
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Skin and subcutaneous tissue disorders
Alopecia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
33.3%
2/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Blood and lymphatic system disorders
Anemia
|
0.00%
0/3
|
66.7%
2/3
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
2/6
|
64.3%
9/14
|
|
Metabolism and nutrition disorders
Anorexia
|
0.00%
0/3
|
66.7%
2/3
|
33.3%
1/3
|
33.3%
2/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Psychiatric disorders
Anxiety
|
33.3%
1/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Investigations
Aspartate aminotransferase increased
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
14.3%
2/14
|
|
Respiratory, thoracic and mediastinal disorders
Atelectasis
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Cardiac disorders
Atrial fibrillation
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Infections and infestations
Fungemia - Candida parapsilosis
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Infections and infestations
Bacteremia - Corynebacterium Species
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Infections and infestations
Bacteremia - Klebsiella
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Infections and infestations
Bacteremia - Staphylococcus epidermis
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Infections and infestations
Bacteremia - Streptococcus agalactiae
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Gastrointestinal disorders
Bloating
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Investigations
Blood bilirubin increased
|
33.3%
1/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
21.4%
3/14
|
|
Eye disorders
Blurred vision
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Musculoskeletal and connective tissue disorders
Bone pain
|
33.3%
1/3
|
33.3%
1/3
|
33.3%
1/3
|
33.3%
2/6
|
50.0%
3/6
|
0.00%
0/14
|
|
General disorders
Chills
|
33.3%
1/3
|
0.00%
0/3
|
33.3%
1/3
|
33.3%
2/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Gastrointestinal disorders
Constipation
|
33.3%
1/3
|
33.3%
1/3
|
33.3%
1/3
|
16.7%
1/6
|
33.3%
2/6
|
7.1%
1/14
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
33.3%
2/6
|
16.7%
1/6
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Dehydration
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Psychiatric disorders
Delirium
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Psychiatric disorders
Depression
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Gastrointestinal disorders
Diarrhea
|
33.3%
1/3
|
33.3%
1/3
|
66.7%
2/3
|
50.0%
3/6
|
33.3%
2/6
|
28.6%
4/14
|
|
Nervous system disorders
Dizziness
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
33.3%
2/6
|
33.3%
2/6
|
7.1%
1/14
|
|
Congenital, familial and genetic disorders
Double uterus
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Gastrointestinal disorders
Dry mouth
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Nervous system disorders
Dysesthesia
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Gastrointestinal disorders
Dyspepsia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Nervous system disorders
Dysphasia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/3
|
33.3%
1/3
|
33.3%
1/3
|
50.0%
3/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Renal and urinary disorders
Dysuria
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
General disorders
Edema: limbs
|
0.00%
0/3
|
0.00%
0/3
|
33.3%
1/3
|
33.3%
2/6
|
16.7%
1/6
|
14.3%
2/14
|
|
Renal and urinary disorders
Enlarged bladder
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Infections and infestations
Enterocolitis infectious
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
0.00%
0/3
|
0.00%
0/3
|
33.3%
1/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Gastrointestinal disorders
Esophageal pain
|
33.3%
1/3
|
0.00%
0/3
|
33.3%
1/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Injury, poisoning and procedural complications
Fall
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
General disorders
Fatigue
|
66.7%
2/3
|
66.7%
2/3
|
33.3%
1/3
|
66.7%
4/6
|
33.3%
2/6
|
7.1%
1/14
|
|
Infections and infestations
Febrile neutropenia
|
100.0%
3/3
|
66.7%
2/3
|
0.00%
0/3
|
33.3%
2/6
|
66.7%
4/6
|
57.1%
8/14
|
|
Gastrointestinal disorders
Fecal incontinence
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
General disorders
Fever
|
0.00%
0/3
|
0.00%
0/3
|
100.0%
3/3
|
83.3%
5/6
|
16.7%
1/6
|
7.1%
1/14
|
|
Eye disorders
Floaters
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Gastrointestinal disorders
Gastroesophageal reflux disease
|
0.00%
0/3
|
66.7%
2/3
|
33.3%
1/3
|
16.7%
1/6
|
16.7%
1/6
|
7.1%
1/14
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
General disorders
Graft versus host disease
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Psychiatric disorders
Hallucinations
|
0.00%
0/3
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Nervous system disorders
Headache
|
33.3%
1/3
|
66.7%
2/3
|
33.3%
1/3
|
66.7%
4/6
|
50.0%
3/6
|
21.4%
3/14
|
|
Renal and urinary disorders
Hematuria
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
14.3%
2/14
|
|
Vascular disorders
Hot flashes
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Hypercalcemia
|
0.00%
0/3
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Metabolism and nutrition disorders
Hyperglycemia
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Hyperkalemia
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Metabolism and nutrition disorders
Hypernatremia
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Nervous system disorders
Hypersomnia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Vascular disorders
Hypertension
|
0.00%
0/3
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Hypoalbuminemia
|
0.00%
0/3
|
100.0%
3/3
|
0.00%
0/3
|
16.7%
1/6
|
33.3%
2/6
|
21.4%
3/14
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
0.00%
0/3
|
66.7%
2/3
|
0.00%
0/3
|
33.3%
2/6
|
83.3%
5/6
|
28.6%
4/14
|
|
Metabolism and nutrition disorders
Hypoglycemia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Metabolism and nutrition disorders
Hypokalemia
|
33.3%
1/3
|
0.00%
0/3
|
33.3%
1/3
|
16.7%
1/6
|
33.3%
2/6
|
42.9%
6/14
|
|
Metabolism and nutrition disorders
Hypomagnesemia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
50.0%
3/6
|
28.6%
4/14
|
|
Metabolism and nutrition disorders
Hyponatremia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
33.3%
2/6
|
21.4%
3/14
|
|
Metabolism and nutrition disorders
Hypophosphatemia
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Vascular disorders
Hypotension
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
16.7%
1/6
|
42.9%
6/14
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Investigations
INR increased
|
0.00%
0/3
|
66.7%
2/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
28.6%
4/14
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Inclusion cyst - mid thoracic back
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Investigations
Increased creatinine
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Psychiatric disorders
Insomnia
|
0.00%
0/3
|
0.00%
0/3
|
33.3%
1/3
|
33.3%
2/6
|
16.7%
1/6
|
21.4%
3/14
|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal hemorrhage
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Infections and infestations
Lip infection
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Infections and infestations
Lung infection
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
33.3%
2/6
|
21.4%
3/14
|
|
Investigations
Lymphocyte count decreased
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
21.4%
3/14
|
|
Investigations
Lymphocyte count increased
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Gastrointestinal disorders
Mucositis oral
|
33.3%
1/3
|
33.3%
1/3
|
33.3%
1/3
|
16.7%
1/6
|
33.3%
2/6
|
0.00%
0/14
|
|
Musculoskeletal and connective tissue disorders
Myalgia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
33.3%
2/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Gastrointestinal disorders
Nausea
|
66.7%
2/3
|
33.3%
1/3
|
100.0%
3/3
|
83.3%
5/6
|
83.3%
5/6
|
57.1%
8/14
|
|
Musculoskeletal and connective tissue disorders
Neck pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Investigations
Neutrophil count decreased
|
0.00%
0/3
|
33.3%
1/3
|
33.3%
1/3
|
16.7%
1/6
|
0.00%
0/6
|
28.6%
4/14
|
|
General disorders
Non-cardiac chest pain
|
0.00%
0/3
|
33.3%
1/3
|
33.3%
1/3
|
16.7%
1/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Gastrointestinal disorders
Oral dysesthesia
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Gastrointestinal disorders
Oral hemorrhage
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Gastrointestinal disorders
Oral pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
|
General disorders
Pain
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
33.3%
2/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Skin and subcutaneous tissue disorders
Papulopustular rash
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Nervous system disorders
Paresthesia
|
0.00%
0/3
|
0.00%
0/3
|
33.3%
1/3
|
33.3%
2/6
|
16.7%
1/6
|
7.1%
1/14
|
|
Nervous system disorders
Peripheral sensory neuropathy
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Gastrointestinal disorders
Perirectal abscess
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Gastrointestinal disorders
Perirectal pain
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Investigations
Platelet count decreased
|
66.7%
2/3
|
33.3%
1/3
|
33.3%
1/3
|
0.00%
0/6
|
33.3%
2/6
|
64.3%
9/14
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
33.3%
1/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Respiratory, thoracic and mediastinal disorders
Pleural hemmorhage
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/3
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/6
|
0.00%
0/6
|
28.6%
4/14
|
|
Respiratory, thoracic and mediastinal disorders
Productive cough
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
21.4%
3/14
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
0.00%
0/3
|
0.00%
0/3
|
33.3%
1/3
|
33.3%
2/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
33.3%
2/6
|
14.3%
2/14
|
|
Gastrointestinal disorders
Rectal pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Gastrointestinal disorders
Rectal ulcer
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Skin and subcutaneous tissue disorders
Scalp pain
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Infections and infestations
Sepsis
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
28.6%
4/14
|
|
Cardiac disorders
Sinus bradycardia
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
16.7%
1/6
|
0.00%
0/14
|
|
Nervous system disorders
Sinus pain
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Cardiac disorders
Sinus tachycardia
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
14.3%
2/14
|
|
Infections and infestations
Skin infection
|
0.00%
0/3
|
0.00%
0/3
|
66.7%
2/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Skin and subcutaneous tissue disorders
Skin ulceration
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
16.7%
1/6
|
7.1%
1/14
|
|
Gastrointestinal disorders
Stomach pain
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Nervous system disorders
Stroke
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Eye disorders
Subconjunctival hemorrhage
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Nervous system disorders
Subdural hematoma
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Musculoskeletal and connective tissue disorders
Submandibular mass
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Nervous system disorders
Syncope
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Nervous system disorders
Tremor
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
7.1%
1/14
|
|
Metabolism and nutrition disorders
Tumor lysis syndrome
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Renal and urinary disorders
Urinary retention
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Infections and infestations
Urinary tract infection
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
16.7%
1/6
|
7.1%
1/14
|
|
Renal and urinary disorders
Urinary urgency
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/3
|
33.3%
1/3
|
66.7%
2/3
|
50.0%
3/6
|
50.0%
3/6
|
28.6%
4/14
|
|
Respiratory, thoracic and mediastinal disorders
Wheezing
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/6
|
0.00%
0/6
|
7.1%
1/14
|
|
Investigations
White blood cell decreased
|
66.7%
2/3
|
0.00%
0/3
|
33.3%
1/3
|
0.00%
0/6
|
33.3%
2/6
|
78.6%
11/14
|
|
Nervous system disorders
Intracranial hemorrhage
|
0.00%
0/3
|
0.00%
0/3
|
0.00%
0/3
|
16.7%
1/6
|
0.00%
0/6
|
0.00%
0/14
|
Additional Information
Geoffrey Uy, M.D.
Washington University School of Medicine
Phone: 314-454-8304
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place