Trial Outcomes & Findings for Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin for Older Patients With Relapsed or Refractory AML (NCT NCT00895934)

NCT ID: NCT00895934

Last Updated: 2019-05-23

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE1/PHASE2

Target enrollment

52 participants

Primary outcome timeframe

42 days

Results posted on

2019-05-23

Participant Flow

Participant milestones

Participant milestones
Measure	Dose Level 1 Azacitidine 75mg/m\^2/day, days 1-7, Vorinostat 200mg/day, days 1-9; and Gemtuzumab Ozogamicin 3mg/m\^2, Day 8 only. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Vorinostat: Given orally Gemtuzumab ozogamicin: Given IV Azacitidine: Given IV or SC laboratory biomarker analysis: Correlative studies	Dose Level 2 Patients receive Azacitidine 75mg/m\^2/day, days 1-7, Vorinostat 300mg/day, days 1-9; and Gemtuzumab Ozogamicin 3mg/m\^2, Day 8 only. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Vorinostat: Given orally Gemtuzumab ozogamicin: Given IV Azacitidine: Given IV or SC laboratory biomarker analysis: Correlative studies	Dose Level 3 Patients receive Azacitidine 75mg/m\^2/day, days 1-7, Vorinostat 400mg/day, days 1-9; and Gemtuzumab Ozogamicin 3mg/m\^2, Day 8 only. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Vorinostat: Given orally Gemtuzumab ozogamicin: Given IV Azacitidine: Given IV or SC laboratory biomarker analysis: Correlative studies	Dose Level 4 Patients receive Azacitidine 75mg/m\^2/day, days 1-7, Vorinostat 400 mg/day, days 1-9; and Gemtuzumab Ozogamicin 3mg/m\^2, Days 4 and 8. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Vorinostat: Given orally Gemtuzumab ozogamicin: Given IV Azacitidine: Given IV or SC laboratory biomarker analysis: Correlative studies
Dose Escalation STARTED	3	3	3	6
Dose Escalation COMPLETED	3	3	3	6
Dose Escalation NOT COMPLETED	0	0	0	0
Efficacy of Most Tolerated Dose STARTED	0	0	0	37
Efficacy of Most Tolerated Dose COMPLETED	0	0	0	37
Efficacy of Most Tolerated Dose NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Vorinostat, Azacitidine, and Gemtuzumab Ozogamicin for Older Patients With Relapsed or Refractory AML

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase 1 Dose-Finding Cohorts 1-3 n=9 Participants Patients receive vorinostat PO on days 1-9, azacitidine SC or IV over 10-40 minutes on days 1-7, and gemtuzumab ozogamicin IV over 2 hours on day 8. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. vorinostat: Given orally gemtuzumab ozogamicin: Given IV azacitidine: Given IV or SC laboratory biomarker analysis: Correlative studies	Phase 2/Selected Dose n=43 Participants Azacitidine 75 mg/m2 SC or IV on days 1-7, vorinostat 400 mg qd po on days 1-9, gemtuzumab ozogamicin 3 mg/m2 IV on days 4 and 8. Includes cohort 4 from the Phase 1 portion of the study. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity.	Total n=52 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	21 Participants n=7 Participants	25 Participants n=5 Participants
Age, Categorical >=65 years	5 Participants n=5 Participants	22 Participants n=7 Participants	27 Participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	18 Participants n=7 Participants	23 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	25 Participants n=7 Participants	29 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	40 Participants n=7 Participants	46 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	6 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	34 Participants n=7 Participants	42 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	9 Participants n=5 Participants	43 Participants n=7 Participants	52 Participants n=5 Participants

PRIMARY outcome

Timeframe: 42 days

Outcome measures

Outcome measures
Measure	Dose 1 n=3 Participants Vorinostat 200, D8	Dose 2 n=3 Participants Vorinostat 300, D8	Dose 3 n=3 Participants Vorinostat 400, D8	Dose 4 n=6 Participants Vorinostat 400, D4 and D8
Number of Participants With Dose-limiting Toxicity (Phase I)	0 participants	0 participants	0 participants	1 participants

PRIMARY outcome

Timeframe: Up to 3 years

Outcome measures

Outcome measures
Measure	Dose 1 n=9 Participants Vorinostat 200, D8	Dose 2 n=43 Participants Vorinostat 300, D8	Dose 3 Vorinostat 400, D8	Dose 4 Vorinostat 400, D4 and D8
Number of Participants With Dose-limiting Toxicity After the Vorinostat Dose	4 participants	18 participants	—	—

SECONDARY outcome

Timeframe: up to 3 years

Efficacy Defined as Best Response Achieved During Study Treatment Measured by Complete Remission (CR) Rate

Outcome measures

Outcome measures
Measure	Dose 1 n=43 Participants Vorinostat 200, D8	Dose 2 Vorinostat 300, D8	Dose 3 Vorinostat 400, D8	Dose 4 Vorinostat 400, D4 and D8
Number of Participants With Complete Remission	18 Participants	—	—	—

SECONDARY outcome

Timeframe: up to 2 years

Outcome measures

Outcome measures
Measure	Dose 1 n=18 Participants Vorinostat 200, D8	Dose 2 Vorinostat 300, D8	Dose 3 Vorinostat 400, D8	Dose 4 Vorinostat 400, D4 and D8
Disease Relapse	5 Participants	—	—	—

Adverse Events

Phase 1 Dose-Finding

Serious events: 6 serious events

Other events: 9 other events

Deaths: 0 deaths

Phase 2

Serious events: 13 serious events

Other events: 43 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Phase 1 Dose-Finding n=15 participants at risk Patients receive vorinostat PO on days 1-9, azacitidine SC or IV over 10-40 minutes on days 1-7, and gemtuzumab ozogamicin IV over 2 hours on day 8. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Laboratory biomarker analysis: correlative studies	Phase 2 n=43 participants at risk Azacitidine 75 mg/m2 on days 1-7, vorinostat 400 mg qd on days 1-9, gemtuzumab ozogamicin 3 mg/m2 on days 4 and 8. Includes cohort 4 from the Phase 1 portion of the study. Laboratory biomarker analysis: correlative studies
Respiratory, thoracic and mediastinal disorders hypoxia	6.7% 1/15 • Number of events 1 • Adverse events are collected from the start of treatment until 30 days after the last dose.	2.3% 1/43 • Number of events 1 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Cardiac disorders hypotension	6.7% 1/15 • Number of events 1 • Adverse events are collected from the start of treatment until 30 days after the last dose.	4.7% 2/43 • Number of events 2 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Infections and infestations infection with neutropenia	6.7% 1/15 • Number of events 2 • Adverse events are collected from the start of treatment until 30 days after the last dose.	2.3% 1/43 • Number of events 2 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Blood and lymphatic system disorders febrile neutropenia	13.3% 2/15 • Number of events 3 • Adverse events are collected from the start of treatment until 30 days after the last dose.	2.3% 1/43 • Number of events 1 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Metabolism and nutrition disorders hypokalemia	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	4.7% 2/43 • Number of events 3 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Infections and infestations sepsis	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	9.3% 4/43 • Number of events 4 • Adverse events are collected from the start of treatment until 30 days after the last dose.
General disorders multi-organ failure	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	2.3% 1/43 • Number of events 1 • Adverse events are collected from the start of treatment until 30 days after the last dose.
General disorders death, NOS	6.7% 1/15 • Number of events 1 • Adverse events are collected from the start of treatment until 30 days after the last dose.	2.3% 1/43 • Number of events 1 • Adverse events are collected from the start of treatment until 30 days after the last dose.

Other adverse events

Additional Information

Roland B. Walter, MD, PhD

Fred Hutchinson Cancer Research Center

Phone: 206-667-3599

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Phase 1 Dose-Finding n=15 participants at risk Patients receive vorinostat PO on days 1-9, azacitidine SC or IV over 10-40 minutes on days 1-7, and gemtuzumab ozogamicin IV over 2 hours on day 8. Treatment repeats every 21 days for up to 12 courses in the absence of disease progression or unacceptable toxicity. Laboratory biomarker analysis: correlative studies	Phase 2 n=43 participants at risk Azacitidine 75 mg/m2 on days 1-7, vorinostat 400 mg qd on days 1-9, gemtuzumab ozogamicin 3 mg/m2 on days 4 and 8. Includes cohort 4 from the Phase 1 portion of the study. Laboratory biomarker analysis: correlative studies
General disorders abdominal pain	6.7% 1/15 • Number of events 1 • Adverse events are collected from the start of treatment until 30 days after the last dose.	11.6% 5/43 • Number of events 6 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Metabolism and nutrition disorders acidosis	6.7% 1/15 • Number of events 1 • Adverse events are collected from the start of treatment until 30 days after the last dose.	4.7% 2/43 • Number of events 2 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Metabolism and nutrition disorders blood chemistry changes	60.0% 9/15 • Number of events 67 • Adverse events are collected from the start of treatment until 30 days after the last dose.	100.0% 43/43 • Number of events 86 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Renal and urinary disorders acute kidney injury	6.7% 1/15 • Number of events 1 • Adverse events are collected from the start of treatment until 30 days after the last dose.	11.6% 5/43 • Number of events 5 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Hepatobiliary disorders elevated liver function tests	40.0% 6/15 • Number of events 14 • Adverse events are collected from the start of treatment until 30 days after the last dose.	34.9% 15/43 • Number of events 32 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Immune system disorders allergic reaction	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	4.7% 2/43 • Number of events 3 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Blood and lymphatic system disorders bleeding	26.7% 4/15 • Number of events 4 • Adverse events are collected from the start of treatment until 30 days after the last dose.	44.2% 19/43 • Number of events 19 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Blood and lymphatic system disorders anemia	53.3% 8/15 • Number of events 11 • Adverse events are collected from the start of treatment until 30 days after the last dose.	58.1% 25/43 • Number of events 33 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Metabolism and nutrition disorders anorexia	6.7% 1/15 • Number of events 1 • Adverse events are collected from the start of treatment until 30 days after the last dose.	53.5% 23/43 • Number of events 34 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Psychiatric disorders anxiety	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	16.3% 7/43 • Number of events 7 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders aspiration	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	9.3% 4/43 • Number of events 4 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Musculoskeletal and connective tissue disorders back pain	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	7.0% 3/43 • Number of events 3 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Blood and lymphatic system disorders pancytopenia	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	30.2% 13/43 • Number of events 17 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Musculoskeletal and connective tissue disorders bone pain	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	4.7% 2/43 • Number of events 2 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Cardiac disorders cardiac chest pain	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	4.7% 2/43 • Number of events 2 • Adverse events are collected from the start of treatment until 30 days after the last dose.
General disorders chills	13.3% 2/15 • Number of events 2 • Adverse events are collected from the start of treatment until 30 days after the last dose.	44.2% 19/43 • Number of events 19 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Gastrointestinal disorders colitis	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	9.3% 4/43 • Number of events 4 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Psychiatric disorders confusion	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	18.6% 8/43 • Number of events 8 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Gastrointestinal disorders constipation	33.3% 5/15 • Number of events 6 • Adverse events are collected from the start of treatment until 30 days after the last dose.	34.9% 15/43 • Number of events 18 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders cough	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	37.2% 16/43 • Number of events 17 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Psychiatric disorders depression	13.3% 2/15 • Number of events 3 • Adverse events are collected from the start of treatment until 30 days after the last dose.	9.3% 4/43 • Number of events 4 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Infections and infestations infection	33.3% 5/15 • Number of events 9 • Adverse events are collected from the start of treatment until 30 days after the last dose.	86.0% 37/43 • Number of events 43 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Gastrointestinal disorders diarrhea	33.3% 5/15 • Number of events 5 • Adverse events are collected from the start of treatment until 30 days after the last dose.	51.2% 22/43 • Number of events 26 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Nervous system disorders dizziness	13.3% 2/15 • Number of events 3 • Adverse events are collected from the start of treatment until 30 days after the last dose.	25.6% 11/43 • Number of events 11 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders dyspnea	6.7% 1/15 • Number of events 1 • Adverse events are collected from the start of treatment until 30 days after the last dose.	32.6% 14/43 • Number of events 14 • Adverse events are collected from the start of treatment until 30 days after the last dose.
General disorders edema	13.3% 2/15 • Number of events 2 • Adverse events are collected from the start of treatment until 30 days after the last dose.	25.6% 11/43 • Number of events 12 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Cardiac disorders prolonged QTc	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	9.3% 4/43 • Number of events 4 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Skin and subcutaneous tissue disorders erythema multiforme	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	7.0% 3/43 • Number of events 3 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Injury, poisoning and procedural complications fall	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	7.0% 3/43 • Number of events 4 • Adverse events are collected from the start of treatment until 30 days after the last dose.
General disorders fatigue	26.7% 4/15 • Number of events 5 • Adverse events are collected from the start of treatment until 30 days after the last dose.	67.4% 29/43 • Number of events 39 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Blood and lymphatic system disorders febrile neutropenia	6.7% 1/15 • Number of events 1 • Adverse events are collected from the start of treatment until 30 days after the last dose.	72.1% 31/43 • Number of events 44 • Adverse events are collected from the start of treatment until 30 days after the last dose.
General disorders fever	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	37.2% 16/43 • Number of events 20 • Adverse events are collected from the start of treatment until 30 days after the last dose.
General disorders pain	20.0% 3/15 • Number of events 4 • Adverse events are collected from the start of treatment until 30 days after the last dose.	32.6% 14/43 • Number of events 15 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Musculoskeletal and connective tissue disorders muscle weakness	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	11.6% 5/43 • Number of events 6 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Nervous system disorders headache	13.3% 2/15 • Number of events 2 • Adverse events are collected from the start of treatment until 30 days after the last dose.	18.6% 8/43 • Number of events 9 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Cardiac disorders hypertension	6.7% 1/15 • Number of events 1 • Adverse events are collected from the start of treatment until 30 days after the last dose.	20.9% 9/43 • Number of events 11 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Cardiac disorders hypotension	13.3% 2/15 • Number of events 2 • Adverse events are collected from the start of treatment until 30 days after the last dose.	20.9% 9/43 • Number of events 9 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders hypoxia	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	18.6% 8/43 • Number of events 9 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Immune system disorders infusion reaction	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	9.3% 4/43 • Number of events 5 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Blood and lymphatic system disorders lymphopenia	26.7% 4/15 • Number of events 6 • Adverse events are collected from the start of treatment until 30 days after the last dose.	0.00% 0/43 • Adverse events are collected from the start of treatment until 30 days after the last dose.
General disorders malaise	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	7.0% 3/43 • Number of events 3 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Gastrointestinal disorders mucositis	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	14.0% 6/43 • Number of events 7 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Gastrointestinal disorders nausea	53.3% 8/15 • Number of events 10 • Adverse events are collected from the start of treatment until 30 days after the last dose.	76.7% 33/43 • Number of events 47 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Blood and lymphatic system disorders neutropenia	20.0% 3/15 • Number of events 4 • Adverse events are collected from the start of treatment until 30 days after the last dose.	39.5% 17/43 • Number of events 26 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Musculoskeletal and connective tissue disorders non-cardiac chest pain	13.3% 2/15 • Number of events 3 • Adverse events are collected from the start of treatment until 30 days after the last dose.	7.0% 3/43 • Number of events 3 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Blood and lymphatic system disorders thrombocytopenia	33.3% 5/15 • Number of events 6 • Adverse events are collected from the start of treatment until 30 days after the last dose.	58.1% 25/43 • Number of events 38 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders pleural effusion	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	11.6% 5/43 • Number of events 5 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Skin and subcutaneous tissue disorders skin disorders	20.0% 3/15 • Number of events 3 • Adverse events are collected from the start of treatment until 30 days after the last dose.	34.9% 15/43 • Number of events 15 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders pulmonary edema	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	9.3% 4/43 • Number of events 4 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders respiratory failure	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	7.0% 3/43 • Number of events 3 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Infections and infestations sepsis	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	20.9% 9/43 • Number of events 9 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Gastrointestinal disorders vomiting	40.0% 6/15 • Number of events 8 • Adverse events are collected from the start of treatment until 30 days after the last dose.	39.5% 17/43 • Number of events 25 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Respiratory, thoracic and mediastinal disorders wheezing	0.00% 0/15 • Adverse events are collected from the start of treatment until 30 days after the last dose.	7.0% 3/43 • Number of events 3 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Blood and lymphatic system disorders leukopenia	40.0% 6/15 • Number of events 7 • Adverse events are collected from the start of treatment until 30 days after the last dose.	53.5% 23/43 • Number of events 32 • Adverse events are collected from the start of treatment until 30 days after the last dose.
Cardiac disorders sinus tachycardia	6.7% 1/15 • Number of events 1 • Adverse events are collected from the start of treatment until 30 days after the last dose.	32.6% 14/43 • Number of events 17 • Adverse events are collected from the start of treatment until 30 days after the last dose.