Trial Outcomes & Findings for Rasburicase in Patients at High Risk for Tumor Lysis Syndrome (TLS) During Cycle-2 (NCT NCT01200485)
NCT ID: NCT01200485
Last Updated: 2020-01-31
Results Overview
Number of participants (incidence) of LTLS in the two arms, as defined by the Cairo-Bishop criteria , during cycle 2. Cairo-Bishop criteria: Uric acid x ≥ 476 μmol/l or 25% increase from baseline Potassium x ≥ 6·0 mmol/l or 25% increase from baseline Phosphorous x ≥ 2·1 mmol/l (children), x ≥1·45 mmol/l (adults) or 25% increase from baseline Calcium x ≤ 1·75 mmol/l or 25% decrease from baseline Laboratory tumour lysis syndrome (LTLS) is defined as either a 25% change or level above or below normal, as defined above, for any two or more serum values of uric acid, potassium, phosphate, and calcium within 3d before or 7d after the initiation of chemotherapy.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
55 participants
Primary outcome timeframe
Up to two 3-week cycles, 6 weeks
Results posted on
2020-01-31
Participant Flow
Recruitment Period: April 25, 2011 to September 10, 2015. All recruitment done at The University of Texas MD Anderson Cancer Center.
Cycle 2 is the study cycle; of the 55 participants enrolled on study, 52 were treated in cycle 1 (rasburicase alone), and only 46 were randomized onto the two arms in the study cycle (cycle 2, Arm A: Rasburicase; Arm B: Allopurinol).
Participant milestones
| Measure |
Cycle 1: Rasburicase Alone
Rasburicase by vein on Day 1 (0.15 mg/kg or a flat dose of 3 mg) as a single dose, plus as needed dosing (until day 5), during cycle 1 (21 day cycle).
|
Cycle 2, Arm A: Rasburicase
Rasburicase (0.15 mg/kg) by vein on day 1 plus as needed dosing (until day 5) during Cycle 2.
|
Cycle 2, Arm B: Allopurinol
Allopurinol (300 mg/day) each day on Days 1-5 of Cycle 2.
|
|---|---|---|---|
|
Cycle 1: Rasburicase Alone Delivery
STARTED
|
55
|
0
|
0
|
|
Cycle 1: Rasburicase Alone Delivery
COMPLETED
|
52
|
0
|
0
|
|
Cycle 1: Rasburicase Alone Delivery
NOT COMPLETED
|
3
|
0
|
0
|
|
Cycle 2: Randomization
STARTED
|
0
|
21
|
25
|
|
Cycle 2: Randomization
COMPLETED
|
0
|
21
|
25
|
|
Cycle 2: Randomization
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
| Measure |
Cycle 1: Rasburicase Alone
Rasburicase by vein on Day 1 (0.15 mg/kg or a flat dose of 3 mg) as a single dose, plus as needed dosing (until day 5), during cycle 1 (21 day cycle).
|
Cycle 2, Arm A: Rasburicase
Rasburicase (0.15 mg/kg) by vein on day 1 plus as needed dosing (until day 5) during Cycle 2.
|
Cycle 2, Arm B: Allopurinol
Allopurinol (300 mg/day) each day on Days 1-5 of Cycle 2.
|
|---|---|---|---|
|
Cycle 1: Rasburicase Alone Delivery
Withdrawal by Subject
|
1
|
0
|
0
|
|
Cycle 1: Rasburicase Alone Delivery
Insurance Coverage Denied
|
2
|
0
|
0
|
Baseline Characteristics
Each row represents continuous age for each randomized arm in Cycle 2, Arm A Rasburicase (N=21) and Arm B Allopurinol (N=25), total 46.
Baseline characteristics by cohort
| Measure |
Rasburicase Alone
n=55 Participants
Rasburicase by vein on Day 1 (0.15 mg/kg or a flat dose of 3 mg) as a single dose, plus as needed dosing (until day 5), during cycle 1
|
|---|---|
|
Age, Continuous
|
54 years
n=55 Participants
|
|
Age, Customized
Cycle 2, Arm A
|
52 years
n=21 Participants • Each row represents continuous age for each randomized arm in Cycle 2, Arm A Rasburicase (N=21) and Arm B Allopurinol (N=25), total 46.
|
|
Age, Customized
Cycle 2, Arm B
|
56 years
n=25 Participants • Each row represents continuous age for each randomized arm in Cycle 2, Arm A Rasburicase (N=21) and Arm B Allopurinol (N=25), total 46.
|
|
Sex: Female, Male
Cycle 1, Rasburicase · Female
|
15 Participants
n=55 Participants • Measure rows divide Cycle 1 (55) then those randomized to Cycle 2 Arm A (21) and Arm B (25).
|
|
Sex: Female, Male
Cycle 1, Rasburicase · Male
|
40 Participants
n=55 Participants • Measure rows divide Cycle 1 (55) then those randomized to Cycle 2 Arm A (21) and Arm B (25).
|
|
Sex: Female, Male
Cycle 2, Arm A · Female
|
5 Participants
n=21 Participants • Measure rows divide Cycle 1 (55) then those randomized to Cycle 2 Arm A (21) and Arm B (25).
|
|
Sex: Female, Male
Cycle 2, Arm A · Male
|
16 Participants
n=21 Participants • Measure rows divide Cycle 1 (55) then those randomized to Cycle 2 Arm A (21) and Arm B (25).
|
|
Sex: Female, Male
Cycle 2, Arm B · Female
|
8 Participants
n=25 Participants • Measure rows divide Cycle 1 (55) then those randomized to Cycle 2 Arm A (21) and Arm B (25).
|
|
Sex: Female, Male
Cycle 2, Arm B · Male
|
17 Participants
n=25 Participants • Measure rows divide Cycle 1 (55) then those randomized to Cycle 2 Arm A (21) and Arm B (25).
|
|
Region of Enrollment
United States
|
55 participants
n=55 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) PS, Cycle 1
<2
|
53 participants
n=55 Participants
|
|
Eastern Cooperative Oncology Group (ECOG) PS, Cycle 1
>/=2
|
2 participants
n=55 Participants
|
|
ECOG PS, Cycle 2
Arm A · <2
|
20 Participants
n=21 Participants • Randomized arms in Cycle 2 Arm A (21) and Arm B (25).
|
|
ECOG PS, Cycle 2
Arm A · >/=2
|
1 Participants
n=21 Participants • Randomized arms in Cycle 2 Arm A (21) and Arm B (25).
|
|
ECOG PS, Cycle 2
Arm B · <2
|
24 Participants
n=25 Participants • Randomized arms in Cycle 2 Arm A (21) and Arm B (25).
|
|
ECOG PS, Cycle 2
Arm B · >/=2
|
1 Participants
n=25 Participants • Randomized arms in Cycle 2 Arm A (21) and Arm B (25).
|
|
Tumor Lysis Syndrome (TLS) Risk
High
|
22 Participants
n=55 Participants
|
|
Tumor Lysis Syndrome (TLS) Risk
Potential
|
30 Participants
n=55 Participants
|
|
Tumor Lysis Syndrome (TLS) Risk
Not evaluable
|
3 Participants
n=55 Participants
|
|
Baseline Plasma Uric Acid (PUA)
Arm A · <7.1 mg/dL
|
16 Participants
n=21 Participants • Randomized Cycle 2 Arm A (21) and Arm B (25).
|
|
Baseline Plasma Uric Acid (PUA)
Arm A · >/=7.1 mg/dL
|
4 Participants
n=21 Participants • Randomized Cycle 2 Arm A (21) and Arm B (25).
|
|
Baseline Plasma Uric Acid (PUA)
Arm A · Not evaluated
|
1 Participants
n=21 Participants • Randomized Cycle 2 Arm A (21) and Arm B (25).
|
|
Baseline Plasma Uric Acid (PUA)
Arm B · <7.1 mg/dL
|
22 Participants
n=25 Participants • Randomized Cycle 2 Arm A (21) and Arm B (25).
|
|
Baseline Plasma Uric Acid (PUA)
Arm B · >/=7.1 mg/dL
|
3 Participants
n=25 Participants • Randomized Cycle 2 Arm A (21) and Arm B (25).
|
|
Baseline Plasma Uric Acid (PUA)
Arm B · Not evaluated
|
0 Participants
n=25 Participants • Randomized Cycle 2 Arm A (21) and Arm B (25).
|
PRIMARY outcome
Timeframe: Up to two 3-week cycles, 6 weeksPopulation: All 46 participants treated in randomized cycle 2 of study were included in analysis.
Number of participants (incidence) of LTLS in the two arms, as defined by the Cairo-Bishop criteria , during cycle 2. Cairo-Bishop criteria: Uric acid x ≥ 476 μmol/l or 25% increase from baseline Potassium x ≥ 6·0 mmol/l or 25% increase from baseline Phosphorous x ≥ 2·1 mmol/l (children), x ≥1·45 mmol/l (adults) or 25% increase from baseline Calcium x ≤ 1·75 mmol/l or 25% decrease from baseline Laboratory tumour lysis syndrome (LTLS) is defined as either a 25% change or level above or below normal, as defined above, for any two or more serum values of uric acid, potassium, phosphate, and calcium within 3d before or 7d after the initiation of chemotherapy.
Outcome measures
| Measure |
Arm A (Rasburicase)
n=21 Participants
Rasburicase (0.15 mg/kg) by vein on day 1 plus as needed dosing (until day 5) during Cycle 2.
|
Arm B (Allopurinol)
n=25 Participants
Allopurinol (300 mg/day) each day on Days 1-5 of Cycle 2.
|
|---|---|---|
|
Number of Participants (Incidence) of LTLS (Laboratory Tumor Lysis Syndrome)
|
1 Participants
|
1 Participants
|
PRIMARY outcome
Timeframe: Up to 24 hours of cycle 2 dose deliveryPopulation: One participant in Arm A missed one UA level assessment.
Number of participants with normalized UAL as determined by a uric acid blood test at either 24 hours. A uric acid blood test, also known as a serum uric acid measurement, determines how much uric acid is present in the blood where normal levels are 2.4-6.0 mg/dL (female) and 3.4-7.0 mg/dL (male).
Outcome measures
| Measure |
Arm A (Rasburicase)
n=21 Participants
Rasburicase (0.15 mg/kg) by vein on day 1 plus as needed dosing (until day 5) during Cycle 2.
|
Arm B (Allopurinol)
n=25 Participants
Allopurinol (300 mg/day) each day on Days 1-5 of Cycle 2.
|
|---|---|---|
|
Number of Cycle 2 Participants Normalizing Uric Acid Levels (UAL) Within 24 Hours of Treatment
|
20 Participants
|
25 Participants
|
Adverse Events
Cycle 1: Rasburicase Alone
Serious events: 3 serious events
Other events: 38 other events
Deaths: 0 deaths
Cycle 2: Arm A (Rasburicase)
Serious events: 1 serious events
Other events: 12 other events
Deaths: 1 deaths
Cycle 2: Arm B (Allopurinol)
Serious events: 1 serious events
Other events: 17 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Cycle 1: Rasburicase Alone
n=52 participants at risk
Rasburicase by vein on Day 1 (0.15 mg/kg or a flat dose of 3 mg) as a single dose, plus as needed dosing (until day 5), during cycle 1 (21 day cycle).
|
Cycle 2: Arm A (Rasburicase)
n=21 participants at risk
Rasburicase (0.15 mg/kg) by vein on day 1 plus as needed dosing (until day 5) during Cycle 2.
|
Cycle 2: Arm B (Allopurinol)
n=25 participants at risk
Allopurinol (300 mg/day) each day on Days 1-5 of Cycle 2.
|
|---|---|---|---|
|
General disorders
Death
|
0.00%
0/52 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
4.8%
1/21 • Number of events 1 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
4.0%
1/25 • Number of events 1 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
|
Blood and lymphatic system disorders
Methemoglobinemia
|
1.9%
1/52 • Number of events 1 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
0.00%
0/21 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
0.00%
0/25 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
|
Renal and urinary disorders
Acute renal failure
|
3.8%
2/52 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
0.00%
0/21 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
0.00%
0/25 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
Other adverse events
| Measure |
Cycle 1: Rasburicase Alone
n=52 participants at risk
Rasburicase by vein on Day 1 (0.15 mg/kg or a flat dose of 3 mg) as a single dose, plus as needed dosing (until day 5), during cycle 1 (21 day cycle).
|
Cycle 2: Arm A (Rasburicase)
n=21 participants at risk
Rasburicase (0.15 mg/kg) by vein on day 1 plus as needed dosing (until day 5) during Cycle 2.
|
Cycle 2: Arm B (Allopurinol)
n=25 participants at risk
Allopurinol (300 mg/day) each day on Days 1-5 of Cycle 2.
|
|---|---|---|---|
|
Gastrointestinal disorders
Constipation
|
44.2%
23/52 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
19.0%
4/21 • Number of events 4 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
36.0%
9/25 • Number of events 9 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
|
Investigations
Blood bilirubin increased
|
11.5%
6/52 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
4.8%
1/21 • Number of events 1 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
16.0%
4/25 • Number of events 4 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
13.5%
7/52 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
4.8%
1/21 • Number of events 1 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
16.0%
4/25 • Number of events 4 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
|
General disorders
Fatigue
|
40.4%
21/52 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
42.9%
9/21 • Number of events 9 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
32.0%
8/25 • Number of events 8 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
|
Nervous system disorders
Headache
|
19.2%
10/52 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
19.0%
4/21 • Number of events 4 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
40.0%
10/25 • Number of events 10 • Adverse events were captured before and after each cycle, up to 30 days from day 1 of the study drug and clinical assessment
|
Additional Information
Saroj Vadhan, MD/Professor, Cytokine & Supportive Oncology
UT MD Anderson Cancer Center
Phone: 713-792-7734
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place