Trial Outcomes & Findings for Pegaspargase and Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia (NCT NCT01005914)
NCT ID: NCT01005914
Last Updated: 2023-01-06
Results Overview
The complete response rate after 1A cycle of a PEG-Asparaginase and hyper-CVAD combination regimen will be estimated, and an exact 95% confidence interval will be computed using a binomial distribution.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
11 participants
Primary outcome timeframe
After day 4 of treatment
Results posted on
2023-01-06
Participant Flow
Participant milestones
| Measure |
Group 1
Drug:cyclophosphamide-Day 1- 3: 300 m g/m2 IV over 2-3 hours every 12 hours for 6 doses plus mesna 600 mg/ m2 /day continuous infusion Days 1-3 Drug:cytarabine Day 2 \& 3: 3g/m2 IV over 2 hours q12 X 4 Drug:dexamethasone Day 1-4; 11-14: 40 mg daily Drug:doxorubicin hydrochloride Day 4: 50 mg/m2 IV over 2 hours Drug:imatinib mesylate 600 mg/day Drug:methotrexate Day 1: 1g/ m2 (200 mg/ m2load IV over 2 hours plus 800 mg/ m2 over 22 hours as an infusion Drug: methylprednisolone Day 1-3: 50mg IV BID Drug: pegaspargase Day 3/Day4: 2,500 IU/ m2 IV Drug: vincristine sulfate Day 4 \& 11: 2 mg IV
cyclophosphamide: Day 1- 3: 300 m g/m2 IV over 2-3 hours every 12 hours for 6 doses plus mesna 600 mg/ m2 /day continuous infusion Days 1-3
cytarabine: Day 2 \& 3: 3g/m2 IV over 2 hours q12 X 4
dexamethasone: Day 1-4; 11-14: 40 mg daily
doxorubicin hydrochloride: Day 4: 50 mg/m2 IV over 2 hours
imatinib mesylate: 600 mg/day
methotrexate: D
|
|---|---|
|
Overall Study
STARTED
|
11
|
|
Overall Study
COMPLETED
|
1
|
|
Overall Study
NOT COMPLETED
|
10
|
Reasons for withdrawal
| Measure |
Group 1
Drug:cyclophosphamide-Day 1- 3: 300 m g/m2 IV over 2-3 hours every 12 hours for 6 doses plus mesna 600 mg/ m2 /day continuous infusion Days 1-3 Drug:cytarabine Day 2 \& 3: 3g/m2 IV over 2 hours q12 X 4 Drug:dexamethasone Day 1-4; 11-14: 40 mg daily Drug:doxorubicin hydrochloride Day 4: 50 mg/m2 IV over 2 hours Drug:imatinib mesylate 600 mg/day Drug:methotrexate Day 1: 1g/ m2 (200 mg/ m2load IV over 2 hours plus 800 mg/ m2 over 22 hours as an infusion Drug: methylprednisolone Day 1-3: 50mg IV BID Drug: pegaspargase Day 3/Day4: 2,500 IU/ m2 IV Drug: vincristine sulfate Day 4 \& 11: 2 mg IV
cyclophosphamide: Day 1- 3: 300 m g/m2 IV over 2-3 hours every 12 hours for 6 doses plus mesna 600 mg/ m2 /day continuous infusion Days 1-3
cytarabine: Day 2 \& 3: 3g/m2 IV over 2 hours q12 X 4
dexamethasone: Day 1-4; 11-14: 40 mg daily
doxorubicin hydrochloride: Day 4: 50 mg/m2 IV over 2 hours
imatinib mesylate: 600 mg/day
methotrexate: D
|
|---|---|
|
Overall Study
Adverse Event
|
4
|
|
Overall Study
Death
|
4
|
|
Overall Study
Lack of Efficacy
|
1
|
|
Overall Study
Withdrawal by Subject
|
1
|
Baseline Characteristics
Pegaspargase and Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Baseline characteristics by cohort
| Measure |
Group 1
n=11 Participants
Drug:cyclophosphamide Day 1- 3: 300 m g/m2 IV over 2-3 hours every 12 hours for 6 doses plus mesna 600 mg/ m2 /day continuous infusion Days 1-3 Drug:cytarabine Day 2 \& 3: 3g/m2 IV over 2 hours q12 X 4 Drug:dexamethasone Day 1-4; 11-14: 40 mg daily
Drug:doxorubicin hydrochloride Day 4: 50 mg/m2 IV over 2 hours
Drug:imatinib mesylate 600 mg/day
Drug:methotrexate Day 1: 1g/ m2 (200 mg/ m2load IV over 2 hours plus 800 mg/ m2 over 22 hours as an infusion
Drug: methylprednisolone Day 1-3: 50mg IV BID
Drug: pegaspargase Day 3/Day4: 2,500 IU/ m2 IV
Drug: vincristine sulfate Day 4 \& 11: 2 mg IV
cyclophosphamide: Day 1- 3: 300 m g/m2 IV over 2-3 hours every 12 hours for 6 doses plus mesna 600 mg/ m2 /day continuous infusion Days 1-3
cytarabine: Day 2 \& 3: 3g/m2 IV over 2 hours q12 X 4
dexamethasone: Day 1-4; 11-14: 40 mg daily
doxorubicin hydrochloride: Day 4: 50 mg/m2 IV over 2 hours
imatinib mesylate: 600 mg/day
methotrexate: D
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
11 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
42.9 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
5 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
11 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: After day 4 of treatmentPopulation: Outcome data for this study was not collected due to early termination of the study due to safety concerns. Only one subject completed the study.
The complete response rate after 1A cycle of a PEG-Asparaginase and hyper-CVAD combination regimen will be estimated, and an exact 95% confidence interval will be computed using a binomial distribution.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: The assessment of safety will be based mainly on the frequency of adverse eventsPopulation: Outcome data for this study was not collected due to early termination of the study due to safety concerns. Only one subject completed the study.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: After completion of 8 cyclesPopulation: Outcome data for this study was not collected due to early termination of the study due to safety concerns. Only one subject completed the study.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: An interim analysis of safety is planned after the enrollment of 15 evaluable patients.Population: Outcome data for this study was not collected due to early termination of the study due to safety concerns. Only one subject completed the study.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: At least every 6 months until death.Population: Outcome data for this study was not collected due to early termination of the study due to safety concerns. Only one subject completed the study.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: End of cycles 1A and 1BPopulation: Outcome data for this study was not collected due to early termination of the study due to safety concerns. Only one subject completed the study.
Cycle 1A: Days 1 through 14 Cycle 1B: Days 1 through 8, after the first 14 days of cycle 1A
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: The approximate t½ in adult patients is 5.73 days. The half-life is independent of the dose administered, disease status, renal or hepatic function, age, or gender.Population: Outcome data for this study was not collected due to early termination of the study due to safety concerns. Only one subject completed the study.
Outcome measures
Outcome data not reported
Adverse Events
Group 1
Serious events: 9 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Group 1
n=11 participants at risk
cyclophosphamide D1- 3: 300 m g/m2 IV 6 doses plus mesna 600 mg/ m2 /day cont. IV D1-3, cytarabine D2 \& 3: 3g/m2 IV, dexD1-4; 11-14: 40 mg daily, doxorubicin hydrochloride D4: 50 mg/m2 IV
Drug:imatinib mesylate 600 mg/day
Drug:methotrexate Day 1: 1g/ m2 (200 mg/ m2load IV over 2 hours plus 800 mg/ m2 over 22 hours as an infusion
Drug: methylprednisolone Day 1-3: 50mg IV BID
Drug: pegaspargase Day 3/Day4: 2,500 IU/ m2 IV
Drug: vincristine sulfate Day 4 \& 11: 2 mg IV
cyclophosphamide: Day 1- 3: 300 m g/m2 IV over 2-3 hours every 12 hours for 6 doses plus mesna 600 mg/ m2 /day continuous infusion Days 1-3
cytarabine: Day 2 \& 3: 3g/m2 IV over 2 hours q12 X 4
dexamethasone: Day 1-4; 11-14: 40 mg daily
doxorubicin hydrochloride: Day 4: 50 mg/m2 IV over 2 hours
imatinib mesylate: 600 mg/day
methotrexate: D
|
|---|---|
|
Infections and infestations
Bacillus species sepsis with encephalitis
|
9.1%
1/11 • Number of events 1 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Cardiac disorders
Chest pain
|
9.1%
1/11 • Number of events 1 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Blood and lymphatic system disorders
neutropenic fever
|
36.4%
4/11 • Number of events 7 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Cardiac disorders
Cardiac Arrest
|
9.1%
1/11 • Number of events 1 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Gastrointestinal disorders
Abdominal pain
|
9.1%
1/11 • Number of events 1 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Infections and infestations
Septic shock
|
18.2%
2/11 • Number of events 2 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Vascular disorders
Pulmonary embolism
|
9.1%
1/11 • Number of events 1 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
General disorders
Death
|
9.1%
1/11 • Number of events 1 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Blood and lymphatic system disorders
hypokalemia, hyponatremia
|
9.1%
1/11 • Number of events 2 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Infections and infestations
fungemia, staph bacteremia
|
9.1%
1/11 • Number of events 1 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Infections and infestations
gnr bacteremia
|
9.1%
1/11 • Number of events 1 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Immune system disorders
anaphylaxis
|
9.1%
1/11 • Number of events 1 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Infections and infestations
acute epiglottitis
|
9.1%
1/11 • Number of events 1 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Infections and infestations
klebsiella bacteremia
|
9.1%
1/11 • Number of events 1 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Gastrointestinal disorders
gastoenteritis
|
9.1%
1/11 • Number of events 1 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Infections and infestations
pneumonia (streptoccocus bacteremia)
|
9.1%
1/11 • Number of events 1 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Infections and infestations
lung infection (fungal)
|
9.1%
1/11 • Number of events 1 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
|
Infections and infestations
alpha-hemolytic streptococcal bacteremia
|
9.1%
1/11 • Number of events 1 • All unexpected adverse events (AEs) related, probably related or possibly related to the study drug which are equal or greater than Grade 3 and serious adverse events (SAEs) were assessed within 30 to 42 days after the last dose of chemotherapy treatment (up to 9 months).
Adverse events collected: 1. Unexpected AEs (when type or severity isn't listed in Expected AE List) 2. Deaths within 30 days of drug admin. 3. Grade ≥ 3 (related to the following): * Allergic reactions * CNS thrombosis/embolism * Coagulopathy * Elevated AST, ALT * Hyperbilirubinemia * Hyperglycemia * Hypertriglyceridemia * Pancreatitis
|
Other adverse events
Adverse event data not reported
Additional Information
Dr. Brandon Hayes-Lattin
Oregon Health & Science University
Phone: 503-494-1551
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place