Trial Outcomes & Findings for Tipifarnib in Treating Patients With Relapsed or Refractory Lymphoma (NCT NCT00082888)

Last Updated: 2020-04-13

Results Overview

Confirmed response is at least a 50% decrease in the sum of the products of the greatest diameters (SPD) of the six largest dominant nodes or nodal masses and no increase in the size of other nodes, liver, or spleen and splenic and hepatic nodules must regress by at least 50% in the SPD and no new sites of disease.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

93 participants

Primary outcome timeframe

During the first 6 cycles of treatment

Results posted on

2020-04-13

Participant Flow

Participants were recruited from 2 medical clinics in the United States between March 2004 to November 2008.

Participant milestones

Participant milestones
Measure	Aggressive B-cell NHL Group Patients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	Indolent B-cell NHL Group Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	HL/T-cell Lymphoma Group Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.
Overall Study STARTED	42	15	36
Overall Study COMPLETED	41	15	36
Overall Study NOT COMPLETED	1	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Aggressive B-cell NHL Group Patients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	Indolent B-cell NHL Group Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	HL/T-cell Lymphoma Group Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.
Overall Study Ineligible	1	0	0

Baseline Characteristics

Tipifarnib in Treating Patients With Relapsed or Refractory Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Aggressive B-cell NHL Group n=42 Participants Patients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	Indolent B-cell NHL Group n=15 Participants Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	HL/T-cell Lymphoma Group n=36 Participants Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	Total n=93 Participants Total of all reporting groups
Age, Continuous	66.5 years n=93 Participants	64.0 years n=4 Participants	48.5 years n=27 Participants	62 years n=483 Participants
Sex: Female, Male Female	18 Participants n=93 Participants	10 Participants n=4 Participants	14 Participants n=27 Participants	42 Participants n=483 Participants
Sex: Female, Male Male	24 Participants n=93 Participants	5 Participants n=4 Participants	22 Participants n=27 Participants	51 Participants n=483 Participants

PRIMARY outcome

Timeframe: During the first 6 cycles of treatment

Population: All participants are included in this analysis.

Outcome measures

Outcome measures
Measure	Aggressive B-cell NHL Group n=42 Participants Patients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	Indolent B-cell NHL Group n=15 Participants Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	HL/T-cell Lymphoma Group n=36 Participants Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.
Proportion of Participants With Confirmed Response (Complete Response, Unconfirmed Complete Response, or Partial Response) During the First 6 Courses of Treatment	0.17 Proportion of participants	0.07 Proportion of participants	0.31 Proportion of participants

SECONDARY outcome

Timeframe: Up to 2 years

Population: All participants are included in this analysis.

Overall survival time was defined as the time from registration to the date of death or last follow-up.

Outcome measures

Outcome measures
Measure	Aggressive B-cell NHL Group n=42 Participants Patients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	Indolent B-cell NHL Group n=15 Participants Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	HL/T-cell Lymphoma Group n=36 Participants Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.
Overall Survival	6.4 months Interval 4.1 to 10.7	20.6 months Interval 16.6 to The 95% confidence interval upper limit was not reached (i.e., insufficient number of participants with events).	19.7 months Interval 9.0 to 60.0

SECONDARY outcome

Timeframe: up to 2 years

Time to progression was defined as the number of months from registration to the date of disease progression with patients being progression-free being censored on the date of their last evaluation. Progression is defined as ≥50 % increase from nadir in the SPD of any previously identified abnormal node for partial responders or nonresponders or appearance of any new lesion during or at the end of therapy.

Outcome measures

Outcome measures
Measure	Aggressive B-cell NHL Group n=42 Participants Patients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	Indolent B-cell NHL Group n=15 Participants Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	HL/T-cell Lymphoma Group n=36 Participants Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.
Time to Progression	2.8 months Interval 1.7 to 4.2	5.2 months Interval 4.0 to 9.2	3.2 months Interval 1.9 to 5.8

SECONDARY outcome

Timeframe: up to 2 years

Population: Patients who had a response were included in this analysis.

Duration of response is defined for all evaluable patients that have achieved an objective response as the date at which the patient's objective status is first noted to be either a complete response (CR) or partial response (PR) to the date progression (PD) is documented. CR:Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms if present before therapy PR:≥50% decrease in SPD of the six largest dominant nodes or nodal masses. PD:≥50 % increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders or appearance of any new lesion during or at the end of therapy.

Outcome measures

Outcome measures
Measure	Aggressive B-cell NHL Group n=7 Participants Patients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	Indolent B-cell NHL Group n=1 Participants Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	HL/T-cell Lymphoma Group n=11 Participants Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.
Duration of Response	11.3 months Interval 4.9 to 17.1	2 months	7.5 months Interval 3.2 to 29.8

SECONDARY outcome

Timeframe: Up to 56 days

Population: Only eligible participants are included in this analysis.

Number of patients that experienced a grade 3 or 4 toxicity (adverse events considered at least possibly related to Tipifarnib) as measured by NCI (National Cancer Institute) CTCAE (Common Terminology Criteria for Adverse Events) v3.0. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL(Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden.). Grade 4: Life-threatening consequences; urgent intervention indicated.

Outcome measures

Outcome measures
Measure	Aggressive B-cell NHL Group n=41 Participants Patients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	Indolent B-cell NHL Group n=15 Participants Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	HL/T-cell Lymphoma Group n=36 Participants Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.
Number of Patients Who Experienced Grade 3 or 4 Toxicities	32 Participants	8 Participants	24 Participants

Adverse Events

Aggressive B-cell NHL Group

Serious events: 27 serious events

Other events: 38 other events

Deaths: 34 deaths

Indolent B-cell NHL Group

Serious events: 4 serious events

Other events: 15 other events

Deaths: 9 deaths

HL/T-cell Lymphoma Group

Serious events: 20 serious events

Other events: 36 other events

Deaths: 27 deaths

Serious adverse events

Other adverse events

Additional Information

Thomas E. Witzig, M.D.

Mayo Clinic

Phone: 507-266-2040

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60

Measure	Aggressive B-cell NHL Group n=41 participants at risk Patients with aggressive B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	Indolent B-cell NHL Group n=15 participants at risk Patients with indolent B-cell NHL receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.	HL/T-cell Lymphoma Group n=36 participants at risk Patients with HL/T-cell lymphoma receive 300mg twice a day for 21 days. Cycle length is 28 days. After cycle 1, may increase the dose to 400mg twice a day or 600mg twice a day at physician discretion.
Blood and lymphatic system disorders Febrile neutropenia	7.3% 3/41 • Number of events 3 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	5.6% 2/36 • Number of events 2 Only eligible participants are included in this analysis.
Blood and lymphatic system disorders Hemoglobin decreased	4.9% 2/41 • Number of events 2 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	5.6% 2/36 • Number of events 2 Only eligible participants are included in this analysis.
Gastrointestinal disorders Abdominal pain	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Gastrointestinal disorders Colonic perforation	0.00% 0/41 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
Gastrointestinal disorders Diarrhea	4.9% 2/41 • Number of events 2 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
Gastrointestinal disorders Gastric ulcer	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Gastrointestinal disorders Mucositis oral (funct/sympt)	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
Gastrointestinal disorders Nausea	4.9% 2/41 • Number of events 2 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Gastrointestinal disorders Vomiting	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
General disorders Death NOS	0.00% 0/41 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
General disorders Disease progression	7.3% 3/41 • Number of events 3 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
General disorders Fatigue	17.1% 7/41 • Number of events 7 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
General disorders Fever	0.00% 0/41 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
General disorders Pain	4.9% 2/41 • Number of events 2 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Hepatobiliary disorders Cholecystitis	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Infections and infestations Bladder infection(unknown ANC)	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Infections and infestations Colitis, infectious	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Infections and infestations Mucosal infection(gr 3/4 ANC)	0.00% 0/41 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
Infections and infestations Pneumonia(gr 0/1/2 ANC)	0.00% 0/41 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	8.3% 3/36 • Number of events 3 Only eligible participants are included in this analysis.
Infections and infestations Sepsis(gr 0/1/2 ANC)	0.00% 0/41 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
Infections and infestations Sepsis(gr 3/4 ANC)	4.9% 2/41 • Number of events 2 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Infections and infestations Sinusitis(gr 0/1/2 ANC)	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Infections and infestations Skin infection	0.00% 0/41 Only eligible participants are included in this analysis.	6.7% 1/15 • Number of events 1 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
Infections and infestations Soft tissue infection(gr 0/1/2 ANC)	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Infections and infestations Upper respiratory infectn(gr 0/1/2 ANC)	0.00% 0/41 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
Infections and infestations Urinary tract infection(gr 0/1/2 ANC)	0.00% 0/41 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 3 Only eligible participants are included in this analysis.
Infections and infestations Wound infection(gr 0/1/2 ANC)	0.00% 0/41 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
Infections and infestations Wound infection(gr 3/4 ANC)	0.00% 0/41 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
Investigations Alanine aminotransferase increased	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Investigations INR increased	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Investigations Leukocyte count decreased	19.5% 8/41 • Number of events 8 Only eligible participants are included in this analysis.	13.3% 2/15 • Number of events 3 Only eligible participants are included in this analysis.	19.4% 7/36 • Number of events 8 Only eligible participants are included in this analysis.
Investigations Lymphocyte count decreased	0.00% 0/41 Only eligible participants are included in this analysis.	6.7% 1/15 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Investigations Neutrophil count decreased	36.6% 15/41 • Number of events 17 Only eligible participants are included in this analysis.	20.0% 3/15 • Number of events 4 Only eligible participants are included in this analysis.	25.0% 9/36 • Number of events 12 Only eligible participants are included in this analysis.
Investigations Platelet count decreased	19.5% 8/41 • Number of events 8 Only eligible participants are included in this analysis.	26.7% 4/15 • Number of events 5 Only eligible participants are included in this analysis.	22.2% 8/36 • Number of events 11 Only eligible participants are included in this analysis.
Metabolism and nutrition disorders Blood bicarbonate decreased	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Metabolism and nutrition disorders Dehydration	7.3% 3/41 • Number of events 3 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
Metabolism and nutrition disorders Serum calcium increased	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Metabolism and nutrition disorders Serum magnesium decreased	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Metabolism and nutrition disorders Serum potassium decreased	4.9% 2/41 • Number of events 2 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Musculoskeletal and connective tissue disorders Back pain	4.9% 2/41 • Number of events 3 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
Musculoskeletal and connective tissue disorders Bone pain	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	0.00% 0/41 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
Nervous system disorders Ataxia	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Nervous system disorders Headache	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Nervous system disorders Mini mental status examination abnormal	0.00% 0/41 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
Nervous system disorders Peripheral motor neuropathy	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Nervous system disorders Speech disorder	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Psychiatric disorders Confusion	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Renal and urinary disorders Hemorrhage urinary tract	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Renal and urinary disorders Ureteric obstruction	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Respiratory, thoracic and mediastinal disorders Dyspnea	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	11.1% 4/36 • Number of events 5 Only eligible participants are included in this analysis.
Respiratory, thoracic and mediastinal disorders Pleuritic pain	0.00% 0/41 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
Respiratory, thoracic and mediastinal disorders Pneumonitis	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	2.8% 1/36 • Number of events 1 Only eligible participants are included in this analysis.
Skin and subcutaneous tissue disorders Urticaria	2.4% 1/41 • Number of events 1 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.
Vascular disorders Hypotension	9.8% 4/41 • Number of events 4 Only eligible participants are included in this analysis.	0.00% 0/15 Only eligible participants are included in this analysis.	0.00% 0/36 Only eligible participants are included in this analysis.