Trial Outcomes & Findings for Hydroxychloroquine, Radiation, and Temozolomide Treating Patients With Newly Diagnosed Glioblastoma Multiforme (NCT NCT00486603)
NCT ID: NCT00486603
Last Updated: 2019-07-10
Results Overview
Number of participants who tolerated doses of HCQ without dose limiting toxicity. The highest dose at which participants did not experience dose limiting toxicity was determined as the MTD.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
92 participants
Primary outcome timeframe
10 weeks
Results posted on
2019-07-10
Participant Flow
This study was conducted by the Adult Brain Tumor Consortium (ABTC) and patients were recruited from the consortium members outpatient centers.
Participant milestones
| Measure |
RT+TMZ+HCQ Phase 1 - 200 mg
Daily Hydroxchloroquine (HCQ) on 1st day of RT and TMZ for 6wks during RT. 200mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
Phse 2: same schema as above but at the prescribed MTD from Phse 1. PKs - correlatives will be collected in Phse 1 and Phse 2
hydroxychloroquine: see arm description, the first 10 week cycle is call initiation cycle, Post the 10 week cycle of just HCQ, 4 week cycles are called Maintenance Cycles
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -wk3-4, wk9-10, Maintenance Cycle 1Week 4 (C1W4), C2W4, C3W4, C6W4
|
RT+TMZ+HCQ Phase 1 - 400 mg
Daily Hydroxchloroquine (HCQ) on 1st day of RT and TMZ for 6wks during RT. 400mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
Phse 2: same schema as above but at the prescribed MTD from Phse 1. PKs - correlatives will be collected in Phse 1 and Phse 2
hydroxychloroquine: see arm description, the first 10 week cycle is call initiation cycle, Post the 10 week cycle of just HCQ, 4 week cycles are called Maintenance Cycles
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -wk3-4, wk9-10, Maintenance Cycle 1Week 4 (C1W4), C2W4, C3W4, C6W4
|
RT+TMZ+HCQ Phase 1 - 600 mg
Daily Hydroxchloroquine (HCQ) on 1st day of RT and TMZ for 6wks during RT. 600mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
Phse 2: same schema as above but at the prescribed MTD from Phse 1. PKs - correlatives will be collected in Phse 1 and Phse 2
hydroxychloroquine: see arm description, the first 10 week cycle is call initiation cycle, Post the 10 week cycle of just HCQ, 4 week cycles are called Maintenance Cycles
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -wk3-4, wk9-10, Maintenance Cycle 1Week 4 (C1W4), C2W4, C3W4, C6W4
|
RT+TMZ+HCQ Phase 1 - 800 mg
Daily Hydroxchloroquine (HCQ) on 1st day of RT and TMZ for 6wks during RT. 800mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
Phse 2: same schema as above but at the prescribed MTD from Phse 1. PKs - correlatives will be collected in Phse 1 and Phse 2
hydroxychloroquine: see arm description, the first 10 week cycle is call initiation cycle, Post the 10 week cycle of just HCQ, 4 week cycles are called Maintenance Cycles
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -wk3-4, wk9-10, Maintenance Cycle 1Week 4 (C1W4), C2W4, C3W4, C6W4
|
RT+TMZ+HCQ Phase 2 - MTD 600 mg
Phse 2: daily hydroxychloroquine (HCQ) (MTD 600mg) on 1st day of RT and concomitant temozolomide for 6wks during RT. After 6 wks, 4 wkd of HCQ alone daily. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
Pts will continue on treatment unitl tumor progression. PKs - correlatives will be collected in Phse 2
Radiation
|
|---|---|---|---|---|---|
|
Overall Study
STARTED
|
3
|
7
|
3
|
3
|
76
|
|
Overall Study
COMPLETED
|
2
|
6
|
3
|
3
|
76
|
|
Overall Study
NOT COMPLETED
|
1
|
1
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
RT+TMZ+HCQ Phase 1 - 200 mg
Daily Hydroxchloroquine (HCQ) on 1st day of RT and TMZ for 6wks during RT. 200mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
Phse 2: same schema as above but at the prescribed MTD from Phse 1. PKs - correlatives will be collected in Phse 1 and Phse 2
hydroxychloroquine: see arm description, the first 10 week cycle is call initiation cycle, Post the 10 week cycle of just HCQ, 4 week cycles are called Maintenance Cycles
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -wk3-4, wk9-10, Maintenance Cycle 1Week 4 (C1W4), C2W4, C3W4, C6W4
|
RT+TMZ+HCQ Phase 1 - 400 mg
Daily Hydroxchloroquine (HCQ) on 1st day of RT and TMZ for 6wks during RT. 400mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
Phse 2: same schema as above but at the prescribed MTD from Phse 1. PKs - correlatives will be collected in Phse 1 and Phse 2
hydroxychloroquine: see arm description, the first 10 week cycle is call initiation cycle, Post the 10 week cycle of just HCQ, 4 week cycles are called Maintenance Cycles
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -wk3-4, wk9-10, Maintenance Cycle 1Week 4 (C1W4), C2W4, C3W4, C6W4
|
RT+TMZ+HCQ Phase 1 - 600 mg
Daily Hydroxchloroquine (HCQ) on 1st day of RT and TMZ for 6wks during RT. 600mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
Phse 2: same schema as above but at the prescribed MTD from Phse 1. PKs - correlatives will be collected in Phse 1 and Phse 2
hydroxychloroquine: see arm description, the first 10 week cycle is call initiation cycle, Post the 10 week cycle of just HCQ, 4 week cycles are called Maintenance Cycles
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -wk3-4, wk9-10, Maintenance Cycle 1Week 4 (C1W4), C2W4, C3W4, C6W4
|
RT+TMZ+HCQ Phase 1 - 800 mg
Daily Hydroxchloroquine (HCQ) on 1st day of RT and TMZ for 6wks during RT. 800mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
Phse 2: same schema as above but at the prescribed MTD from Phse 1. PKs - correlatives will be collected in Phse 1 and Phse 2
hydroxychloroquine: see arm description, the first 10 week cycle is call initiation cycle, Post the 10 week cycle of just HCQ, 4 week cycles are called Maintenance Cycles
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -wk3-4, wk9-10, Maintenance Cycle 1Week 4 (C1W4), C2W4, C3W4, C6W4
|
RT+TMZ+HCQ Phase 2 - MTD 600 mg
Phse 2: daily hydroxychloroquine (HCQ) (MTD 600mg) on 1st day of RT and concomitant temozolomide for 6wks during RT. After 6 wks, 4 wkd of HCQ alone daily. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
Pts will continue on treatment unitl tumor progression. PKs - correlatives will be collected in Phse 2
Radiation
|
|---|---|---|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
0
|
0
|
0
|
|
Overall Study
Physician Decision
|
0
|
1
|
0
|
0
|
0
|
Baseline Characteristics
Hydroxychloroquine, Radiation, and Temozolomide Treating Patients With Newly Diagnosed Glioblastoma Multiforme
Baseline characteristics by cohort
| Measure |
RT+TMZ+HCQ Phase 1
n=16 Participants
Phse I: daily Hydroxychloroquine (HCQ) on 1st day of RT and concomitant TMZ for 6wks during RT. Starting dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. then every 4 weeks will be cycle of mono therapy of HCQ daily.
cohorts of three pts: dose levels: 200, 400, 600, 800mg. NO dose escalation beyond 800mg.
hydroxychloroquine: see arm description, the first 10 week cycle is call initiation cycle, Post the 10 week cycle of just HCQ, 4 week cycles are called Maintenance Cycles
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ TMZ days 1-5 150-20mg/m2 cycles 1-6
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation 6weeks during initiation cycle Monday - Friday
|
RT+TMZ+HCQ Phase 2
n=76 Participants
Daily hydroxychloroquine (HCQ) (MTD 600mg) on 1st day of RT and temozolomide for 6wks during RT. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ TMZ D1-5 150-20mg/m2 cycles 1-6
pharmacological study/Correlative study: Seven samples in total collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation 6weeks during initiation cycle Monday - Friday
Pts will continue on treatment unti/tumor progression.
|
Total
n=92 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
55 years
n=93 Participants
|
59 years
n=4 Participants
|
58 years
n=27 Participants
|
|
Sex: Female, Male
Female
|
4 Participants
n=93 Participants
|
30 Participants
n=4 Participants
|
34 Participants
n=27 Participants
|
|
Sex: Female, Male
Male
|
12 Participants
n=93 Participants
|
46 Participants
n=4 Participants
|
58 Participants
n=27 Participants
|
|
Karnofsky Performance Status
100
|
5 Participants
n=93 Participants
|
15 Participants
n=4 Participants
|
20 Participants
n=27 Participants
|
|
Karnofsky Performance Status
90
|
7 Participants
n=93 Participants
|
31 Participants
n=4 Participants
|
38 Participants
n=27 Participants
|
|
Karnofsky Performance Status
80
|
3 Participants
n=93 Participants
|
18 Participants
n=4 Participants
|
21 Participants
n=27 Participants
|
|
Karnofsky Performance Status
70
|
1 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
11 Participants
n=27 Participants
|
|
Karnofsky Performance Status
60
|
0 Participants
n=93 Participants
|
2 Participants
n=4 Participants
|
2 Participants
n=27 Participants
|
|
Surgical Procedure
Biopsy
|
6 Participants
n=93 Participants
|
18 Participants
n=4 Participants
|
24 Participants
n=27 Participants
|
|
Surgical Procedure
Craniotomy
|
10 Participants
n=93 Participants
|
58 Participants
n=4 Participants
|
68 Participants
n=27 Participants
|
PRIMARY outcome
Timeframe: 10 weeksPopulation: Cohort 200mg - 3 subjects ; cohort 400mg - 7 subjects; 600mg - 3 subjects; 800mg - 3 subjects
Number of participants who tolerated doses of HCQ without dose limiting toxicity. The highest dose at which participants did not experience dose limiting toxicity was determined as the MTD.
Outcome measures
| Measure |
Phase 1 - Dose Finding
n=16 Participants
Phse I: daily Hydroxychloroquine (HCQ) on 1st day of RT and concomitant TMZ for 6wks during RT. Starting dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
cohorts of three pts: dose levels: 200, 400, 600mg 800mg. NO dose escalation beyond 800mg.
temozolomide: TMZ daily 75mg/m2 for 6weeks with RT+HCQ TMZ Maintenance cycle 1-6 150-200mg/m2
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4 (C2W4), Cycle3 Week4 (C3W4), Cycle6 Week4 (C6W4)
Radiation 6weeks during initation cycle Monday - Friday
|
Phase 1: RT+TMZ+HCQ - 400mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 400mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 600mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 800mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 800mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
|---|---|---|---|---|
|
(Phase I) Maximum Tolerated Dose (MTD) of Hydroxychloroquine (HCQ)
400mg
|
7 Participants
|
—
|
—
|
—
|
|
(Phase I) Maximum Tolerated Dose (MTD) of Hydroxychloroquine (HCQ)
200mg
|
3 Participants
|
—
|
—
|
—
|
|
(Phase I) Maximum Tolerated Dose (MTD) of Hydroxychloroquine (HCQ)
600mg
|
3 Participants
|
—
|
—
|
—
|
|
(Phase I) Maximum Tolerated Dose (MTD) of Hydroxychloroquine (HCQ)
800mg
|
0 Participants
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 10 weeksPopulation: 1/7 subjects from the 400mg cohort only received 70% of expected dose, therefore this subject was not used for toxicity analysis
Dose limiting toxicity defined as: Any DLT must be a toxicity considered at least possibly related to HCQ. DLTs will include any possibly, probably, or definitely HCQ-related Grade 3 or 4 toxicity. Known or reasonably suspected TMZ hematological toxicities will not be considered dose limiting unless the treating physician considers the toxicity to be exacerbated by HCQ. Nonhematological toxicities: Any Grades 3-4 severity (except nausea and vomiting without sufficient antiemetic prophylaxis)
Outcome measures
| Measure |
Phase 1 - Dose Finding
n=3 Participants
Phse I: daily Hydroxychloroquine (HCQ) on 1st day of RT and concomitant TMZ for 6wks during RT. Starting dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
cohorts of three pts: dose levels: 200, 400, 600mg 800mg. NO dose escalation beyond 800mg.
temozolomide: TMZ daily 75mg/m2 for 6weeks with RT+HCQ TMZ Maintenance cycle 1-6 150-200mg/m2
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4 (C2W4), Cycle3 Week4 (C3W4), Cycle6 Week4 (C6W4)
Radiation 6weeks during initation cycle Monday - Friday
|
Phase 1: RT+TMZ+HCQ - 400mg
n=6 Participants
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 400mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 600mg
n=3 Participants
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 800mg
n=3 Participants
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 800mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
|---|---|---|---|---|
|
(Phase I) Number of Participants Who Experienced Dose Limiting Toxicity (DLT)
|
0 Participants
|
0 Participants
|
0 Participants
|
3 Participants
|
PRIMARY outcome
Timeframe: 2 yearsPopulation: Only Phase 2 participants were assessed for this outcome measure.
Number of months alive after end of study participation
Outcome measures
| Measure |
Phase 1 - Dose Finding
n=76 Participants
Phse I: daily Hydroxychloroquine (HCQ) on 1st day of RT and concomitant TMZ for 6wks during RT. Starting dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
cohorts of three pts: dose levels: 200, 400, 600mg 800mg. NO dose escalation beyond 800mg.
temozolomide: TMZ daily 75mg/m2 for 6weeks with RT+HCQ TMZ Maintenance cycle 1-6 150-200mg/m2
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4 (C2W4), Cycle3 Week4 (C3W4), Cycle6 Week4 (C6W4)
Radiation 6weeks during initation cycle Monday - Friday
|
Phase 1: RT+TMZ+HCQ - 400mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 400mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 600mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 800mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 800mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
|---|---|---|---|---|
|
(Phase II) Overall Survival
|
15.6 months
Interval 13.0 to 17.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 2 yearsPopulation: Only participants from Phase II were assessed for this outcome measure.
Number of participants experiencing Grade 3 and 4 toxicity, as defined by CTCAE v3.0, with a possible, probable or definite relationship to HCQ, TMZ or both
Outcome measures
| Measure |
Phase 1 - Dose Finding
n=76 Participants
Phse I: daily Hydroxychloroquine (HCQ) on 1st day of RT and concomitant TMZ for 6wks during RT. Starting dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
cohorts of three pts: dose levels: 200, 400, 600mg 800mg. NO dose escalation beyond 800mg.
temozolomide: TMZ daily 75mg/m2 for 6weeks with RT+HCQ TMZ Maintenance cycle 1-6 150-200mg/m2
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4 (C2W4), Cycle3 Week4 (C3W4), Cycle6 Week4 (C6W4)
Radiation 6weeks during initation cycle Monday - Friday
|
Phase 1: RT+TMZ+HCQ - 400mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 400mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 600mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 800mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 800mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
|---|---|---|---|---|
|
(Phase II) Number of Participants With Grade 3 and 4 Toxicity
|
22 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 9 weeksPopulation: Only 40 participants had at least 2 PBMC samples that were amenable to EM, which was required to assess this outcome measure.
Number of participants with at least 2 peripheral blood mononuclear cell (PBMC) samples that were amenable to electronmicroscopy (EM) who showed an increase of autophagic vacuoles in cells.
Outcome measures
| Measure |
Phase 1 - Dose Finding
n=40 Participants
Phse I: daily Hydroxychloroquine (HCQ) on 1st day of RT and concomitant TMZ for 6wks during RT. Starting dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
cohorts of three pts: dose levels: 200, 400, 600mg 800mg. NO dose escalation beyond 800mg.
temozolomide: TMZ daily 75mg/m2 for 6weeks with RT+HCQ TMZ Maintenance cycle 1-6 150-200mg/m2
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4 (C2W4), Cycle3 Week4 (C3W4), Cycle6 Week4 (C6W4)
Radiation 6weeks during initation cycle Monday - Friday
|
Phase 1: RT+TMZ+HCQ - 400mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 400mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 600mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 800mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 800mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
|---|---|---|---|---|
|
Pharmocodynamics as Determined by Number of Participants With Autophagy Inhibition
AV increase
|
22 Participants
|
—
|
—
|
—
|
|
Pharmocodynamics as Determined by Number of Participants With Autophagy Inhibition
No AV increase
|
18 Participants
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 9 weeksPopulation: Only participants who had at least 2 PBMC samples that were amenable to EM were assessed for this outcome measure
Autophagy inhibition is represented by an increase in autophagic vacuoles (AV) in participants with at least 2 peripheral blood mononuclear cell samples that were amenable to EM.
Outcome measures
| Measure |
Phase 1 - Dose Finding
n=22 Participants
Phse I: daily Hydroxychloroquine (HCQ) on 1st day of RT and concomitant TMZ for 6wks during RT. Starting dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
cohorts of three pts: dose levels: 200, 400, 600mg 800mg. NO dose escalation beyond 800mg.
temozolomide: TMZ daily 75mg/m2 for 6weeks with RT+HCQ TMZ Maintenance cycle 1-6 150-200mg/m2
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4 (C2W4), Cycle3 Week4 (C3W4), Cycle6 Week4 (C6W4)
Radiation 6weeks during initation cycle Monday - Friday
|
Phase 1: RT+TMZ+HCQ - 400mg
n=18 Participants
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 400mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 600mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 800mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 800mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
|---|---|---|---|---|
|
Pharmocodynamics as Determined by Number of Participants With Autophagy Inhibition in Relation to Maximal Concentration (Cmax) of HCQ
AV Increase
|
10 Participants
|
12 Participants
|
—
|
—
|
|
Pharmocodynamics as Determined by Number of Participants With Autophagy Inhibition in Relation to Maximal Concentration (Cmax) of HCQ
No AV Increase
|
12 Participants
|
6 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 276 daysPopulation: Only participants from Phase II were assessed for this outcome measure. Data was not collected from 4/76 participants.
The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model.
Outcome measures
| Measure |
Phase 1 - Dose Finding
n=72 Participants
Phse I: daily Hydroxychloroquine (HCQ) on 1st day of RT and concomitant TMZ for 6wks during RT. Starting dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
cohorts of three pts: dose levels: 200, 400, 600mg 800mg. NO dose escalation beyond 800mg.
temozolomide: TMZ daily 75mg/m2 for 6weeks with RT+HCQ TMZ Maintenance cycle 1-6 150-200mg/m2
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4 (C2W4), Cycle3 Week4 (C3W4), Cycle6 Week4 (C6W4)
Radiation 6weeks during initation cycle Monday - Friday
|
Phase 1: RT+TMZ+HCQ - 400mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 400mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 600mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 800mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 800mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
|---|---|---|---|---|
|
Pharmacokinetics (PK) of Hydroxychloroquine as Measured by Lag Time (Tlag)
|
1.06 hour
Interval 0.97 to 1.25
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 276 daysPopulation: Only participants from Phase II were assessed for this outcome measure. Data was not collected from 4/76 participants.
The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model.
Outcome measures
| Measure |
Phase 1 - Dose Finding
n=72 Participants
Phse I: daily Hydroxychloroquine (HCQ) on 1st day of RT and concomitant TMZ for 6wks during RT. Starting dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
cohorts of three pts: dose levels: 200, 400, 600mg 800mg. NO dose escalation beyond 800mg.
temozolomide: TMZ daily 75mg/m2 for 6weeks with RT+HCQ TMZ Maintenance cycle 1-6 150-200mg/m2
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4 (C2W4), Cycle3 Week4 (C3W4), Cycle6 Week4 (C6W4)
Radiation 6weeks during initation cycle Monday - Friday
|
Phase 1: RT+TMZ+HCQ - 400mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 400mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 600mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 800mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 800mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
|---|---|---|---|---|
|
PK of Hydroxychloroquine as Measured by Oral Clearance (Liters/Hour) From Central Compartment (CL/F)
|
11.85 L/hr
Interval 6.41 to 28.18
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 276 daysPopulation: Only participants from Phase II were assessed for this outcome measure. Data was not collected from 4/76 participants.
The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model.
Outcome measures
| Measure |
Phase 1 - Dose Finding
n=72 Participants
Phse I: daily Hydroxychloroquine (HCQ) on 1st day of RT and concomitant TMZ for 6wks during RT. Starting dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
cohorts of three pts: dose levels: 200, 400, 600mg 800mg. NO dose escalation beyond 800mg.
temozolomide: TMZ daily 75mg/m2 for 6weeks with RT+HCQ TMZ Maintenance cycle 1-6 150-200mg/m2
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4 (C2W4), Cycle3 Week4 (C3W4), Cycle6 Week4 (C6W4)
Radiation 6weeks during initation cycle Monday - Friday
|
Phase 1: RT+TMZ+HCQ - 400mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 400mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 600mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 800mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 800mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
|---|---|---|---|---|
|
PK of Hydroxychloroquine as Measured by Volume of Distribution of Central Compartment (V/F)
|
483.96 Liters
Interval 26.0 to 5483.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 276 daysPopulation: Only participants from Phase II were assessed for this outcome measure. Data was not collected from 4/76 participants.
The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model.
Outcome measures
| Measure |
Phase 1 - Dose Finding
n=72 Participants
Phse I: daily Hydroxychloroquine (HCQ) on 1st day of RT and concomitant TMZ for 6wks during RT. Starting dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
cohorts of three pts: dose levels: 200, 400, 600mg 800mg. NO dose escalation beyond 800mg.
temozolomide: TMZ daily 75mg/m2 for 6weeks with RT+HCQ TMZ Maintenance cycle 1-6 150-200mg/m2
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4 (C2W4), Cycle3 Week4 (C3W4), Cycle6 Week4 (C6W4)
Radiation 6weeks during initation cycle Monday - Friday
|
Phase 1: RT+TMZ+HCQ - 400mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 400mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 600mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 800mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 800mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
|---|---|---|---|---|
|
PK of Hydroxychloroquine as Measured by Distribution Volume of Peripheral Compartment (V2/F)
|
963 Liters
Interval 558.0 to 2208.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: up to 276 daysPopulation: Only participants from Phase II were assessed for this outcome measure. Data was not collected from 4/76 participants.
The population model PK parameters do not specifically represent steady-state values, as they were determined from multiple repeated single doses taken from multiple repeated doses taken by the individual patient during their period on the study. To obtain steady state PK parameters, individual estimates were simulated from the population model.
Outcome measures
| Measure |
Phase 1 - Dose Finding
n=72 Participants
Phse I: daily Hydroxychloroquine (HCQ) on 1st day of RT and concomitant TMZ for 6wks during RT. Starting dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. Complete 10 week cycle -Initiation Phase
Maintenance cycles 1-6 HCQ daily TMZ D 1-5 150-200mg/m2 every 28 days. Cycles 7+ mono therapy of HCQ daily, every 28 days.
cohorts of three pts: dose levels: 200, 400, 600mg 800mg. NO dose escalation beyond 800mg.
temozolomide: TMZ daily 75mg/m2 for 6weeks with RT+HCQ TMZ Maintenance cycle 1-6 150-200mg/m2
pharmacological study/Correlative study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4 (C2W4), Cycle3 Week4 (C3W4), Cycle6 Week4 (C6W4)
Radiation 6weeks during initation cycle Monday - Friday
|
Phase 1: RT+TMZ+HCQ - 400mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 400mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 600mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 800mg
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 800mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
|---|---|---|---|---|
|
PK of Hydroxychloroquine as Measured by First-order Absorption Rate Constant (Ka)
|
0.51 hours
Interval 0.42 to 0.82
|
—
|
—
|
—
|
Adverse Events
Phase 1: RT+TMZ+HCQ - 200mg
Serious events: 1 serious events
Other events: 3 other events
Deaths: 0 deaths
Phase 1: RT+TMZ+HCQ - 400mg
Serious events: 7 serious events
Other events: 7 other events
Deaths: 0 deaths
Phase 1: RT+TMZ+HCQ - 600mg
Serious events: 3 serious events
Other events: 3 other events
Deaths: 0 deaths
Phase 1: RT+TMZ+HCQ - 800mg
Serious events: 3 serious events
Other events: 3 other events
Deaths: 0 deaths
Phase 2: RT+TMZ+HCQ - MTD 600mg
Serious events: 53 serious events
Other events: 76 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Phase 1: RT+TMZ+HCQ - 200mg
n=3 participants at risk
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 400mg
n=7 participants at risk
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 400mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 600mg
n=3 participants at risk
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 800mg
n=3 participants at risk
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 800mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 2: RT+TMZ+HCQ - MTD 600mg
n=76 participants at risk
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg MTD. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
abdominal pain
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
alanine aminotransferase increased
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
2.6%
2/76 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
alkaline phosphatase increased
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
28.6%
2/7 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
7.9%
6/76 • Number of events 6 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Blood and lymphatic system disorders
anemia
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
100.0%
3/3 • Number of events 4 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
3.9%
3/76 • Number of events 3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Metabolism and nutrition disorders
anorexia
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
blood bilirubin increased
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Gastrointestinal disorders
constipation
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Eye disorders
decreased depth perception
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
General disorders
fatigue
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Blood and lymphatic system disorders
febrile neutropenia
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Musculoskeletal and connective tissue disorders
generalized muscle weakness
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Blood and lymphatic system disorders
hemolysis
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Metabolism and nutrition disorders
hyperkalemia
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Metabolism and nutrition disorders
hyperuricemia
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Infections and infestations
other
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
lymphocyte count decreased
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Gastrointestinal disorders
nausea
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
neutrophil count decreased
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
28.6%
2/7 • Number of events 3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
66.7%
2/3 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
10.5%
8/76 • Number of events 10 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Skin and subcutaneous tissue disorders
rash maculo-papular
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
11.8%
9/76 • Number of events 9 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Metabolism and nutrition disorders
white blood cell count decreased
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
66.7%
2/3 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
10.5%
8/76 • Number of events 8 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
platelet count decreased
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
100.0%
3/3 • Number of events 4 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
11.8%
9/76 • Number of events 11 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
Other adverse events
| Measure |
Phase 1: RT+TMZ+HCQ - 200mg
n=3 participants at risk
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 200mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 400mg
n=7 participants at risk
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 400mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 600mg
n=3 participants at risk
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 1: RT+TMZ+HCQ - 800mg
n=3 participants at risk
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 800mg. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
Phase 2: RT+TMZ+HCQ - MTD 600mg
n=76 participants at risk
Daily hydroxychloroquine (HCQ) on 1st day of RT and concomitant temozolomide for 6wks during RT. Dose of HCQ is 600mg MTD. After 6 wks, 4 wkd of HCQ alone daily. this will complete 10 week cycle. -Initiation Phase
temozolomide: TMZ daily 75mg/m2 for 6wks with RT+HCQ (TMZ is given only during Initiation cycle)
pharmacological study: Seven samples in total will be collected baseline, initiation cycle -week3-4, week9-10, Maintenance Cycle 1 Week 4 (C1W4), Cycle2 Week4, Cycle3 Week4, Cycle6 Week4
Radiation: Radiation during the first six weeks of treatment Monday-Friday
|
|---|---|---|---|---|---|
|
Gastrointestinal disorders
abdominal distension
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Psychiatric disorders
mood alteration
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
alanine aminotransferase increased
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
28.6%
2/7 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
18.4%
14/76 • Number of events 14 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
alkaline phosphatase increased
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
28.6%
2/7 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
7.9%
6/76 • Number of events 6 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Skin and subcutaneous tissue disorders
alopecia
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Blood and lymphatic system disorders
anemia
|
100.0%
3/3 • Number of events 3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
42.9%
3/7 • Number of events 4 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
100.0%
3/3 • Number of events 4 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
48.7%
37/76 • Number of events 38 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Metabolism and nutrition disorders
anorexia
|
66.7%
2/3 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
28.6%
2/7 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
19.7%
15/76 • Number of events 15 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Psychiatric disorders
anxiety
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
aspartate aminotransferase increased
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.5%
11/76 • Number of events 11 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Nervous system disorders
ataxia
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Gastrointestinal disorders
bloating
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
blood bilirubin increased
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
5.3%
4/76 • Number of events 4 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Injury, poisoning and procedural complications
bruising
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Eye disorders
blurred vision
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
2.6%
2/76 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
General disorders
chills
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
2.6%
2/76 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Gastrointestinal disorders
constipation
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
15.8%
12/76 • Number of events 12 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
creatinine increased
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
2.6%
2/76 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Psychiatric disorders
depression
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Gastrointestinal disorders
diarrhea
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
28.6%
2/7 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
66.7%
2/3 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
18.4%
14/76 • Number of events 14 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Skin and subcutaneous tissue disorders
dry skin
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Nervous system disorders
dysarthria
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Nervous system disorders
dizziness
|
66.7%
2/3 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Nervous system disorders
dysgeusia
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
6.6%
5/76 • Number of events 5 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Gastrointestinal disorders
dyspepsia
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
6.6%
5/76 • Number of events 5 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
General disorders
edema limbs
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Respiratory, thoracic and mediastinal disorders
epistaxis
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Skin and subcutaneous tissue disorders
erythema multiforme
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Gastrointestinal disorders
esophageal pain
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Eye disorders
other
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
General disorders
fatigue
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
71.4%
5/7 • Number of events 6 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
66.7%
2/3 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
66.7%
2/3 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
57.9%
44/76 • Number of events 47 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
General disorders
feber
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Gastrointestinal disorders
gastric hemorrhage
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Gastrointestinal disorders
gastroesophageal reflux disease
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
2.6%
2/76 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Musculoskeletal and connective tissue disorders
generalized muscle weakness
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Nervous system disorders
headache
|
66.7%
2/3 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
2.6%
2/76 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Metabolism and nutrition disorders
hyperkalemia
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Metabolism and nutrition disorders
hyperuricemia
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Metabolism and nutrition disorders
hypocalcemia
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
3.9%
3/76 • Number of events 3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Metabolism and nutrition disorders
hypokalemia
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Metabolism and nutrition disorders
hypomagnesemia
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Metabolism and nutrition disorders
hyponatremia
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
3.9%
3/76 • Number of events 3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Vascular disorders
hypotension
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
other
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
2.6%
2/76 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Infections and infestations
other
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Psychiatric disorders
insomnia
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Psychiatric disorders
irritability
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
lipase increased
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
lymphocyte count decreased
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
General disorders
malaise
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Nervous system disorders
memory impairment
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Gastrointestinal disorders
mucositis oral
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
2.6%
2/76 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Musculoskeletal and connective tissue disorders
muscle weakness lower limb
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Gastrointestinal disorders
nausea
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
71.4%
5/7 • Number of events 6 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
46.1%
35/76 • Number of events 38 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
neutrophil count decreased
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
13.2%
10/76 • Number of events 10 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
General disorders
pain
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Musculoskeletal and connective tissue disorders
pain in extremity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Nervous system disorders
peripheral sensory neuropathy
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Skin and subcutaneous tissue disorders
photosensitivity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Skin and subcutaneous tissue disorders
Pruritus
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
9.2%
7/76 • Number of events 7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Skin and subcutaneous tissue disorders
purpura
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/76 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Skin and subcutaneous tissue disorders
rash acneiform
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
platelet count decreased
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
42.9%
3/7 • Number of events 3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
66.7%
2/3 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
66.7%
2/3 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
39.5%
30/76 • Number of events 32 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Skin and subcutaneous tissue disorders
rash maculo-papular
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
14.3%
1/7 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
11.8%
9/76 • Number of events 10 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Investigations
serum amylase increased
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
1.3%
1/76 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Gastrointestinal disorders
stomach pain
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
2.6%
2/76 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Gastrointestinal disorders
vomiting
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
28.6%
2/7 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
66.7%
2/3 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
17.1%
13/76 • Number of events 13 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Metabolism and nutrition disorders
weight loss
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/7 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
0.00%
0/3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
2.6%
2/76 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
|
Metabolism and nutrition disorders
white blood cell count decreased
|
33.3%
1/3 • Number of events 1 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
28.6%
2/7 • Number of events 4 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
66.7%
2/3 • Number of events 2 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
66.7%
2/3 • Number of events 3 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
35.5%
27/76 • Number of events 27 • 3 years
Adverse events not serious are defined as having Grade 1 and Grade 2 severity
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: GT60