Pegaspargase and Combination Chemotherapy in Treating Pat... | NCT01005914

NCT01005914

ID	Type	Description
OHSU-4913	Other Identifier	OHSU IRB
ENZON-OHSU-4913	Other Identifier	OHSU
CDR0000642363	Other Identifier	NCI PDQ

Status Module

Sponsor/Collaborators Module

Oversight Module

Description Module

Detailed Description

OBJECTIVES:

Primary

To estimate the complete response rate in patients with newly diagnosed acute lymphoblastic leukemia treated with pegaspargase in combination with hyper-CVAD regimen comprising cyclophosphamide, dexamethasone, vincristine sulfate, doxorubicin hydrochloride, methotrexate, and cytarabine.
To determine the safety and tolerability of this regimen in these patients.

Secondary

To evaluate the progression-free survival and overall survival of patients treated with this regimen.
To determine the half-life of pegaspargase when administered in combination with hyper-CVAD regimen.
To monitor the development of neutralizing antibodies to pegaspargase when administered in combination with hyper-CVAD regimen.
To assess minimal residual disease by flow cytometry at the end of courses 1A and 1B.

OUTLINE: This is a multicenter study.

Hyper-CVAD regimen (courses 1, 3, 5, and 7): Patients receive cyclophosphamide IV over 2-3 hours twice daily on days 1-3, dexamethasone IV on days 1-4 and 11-14, methotrexate intrathecally (IT) on day 2, doxorubicin hydrochloride IV over 2 hours and pegaspargase IV over 1-2 hours on day 4, vincristine sulfate IV on days 4 and 11, and cytarabine IT on day 8.
High-dose methotrexate/cytarabine regimen (courses 2, 4, 6, and 8): Patients receive methotrexate IV continuously over 24 hours on day 1, methylprednisolone IV twice daily on days 1-3, methotrexate IT on day 2, cytarabine IV over 2 hours twice daily on days 2 and 3, pegaspargase IV over 1-2 hours on day 3, and cytarabine IT on day 8.

Treatment repeats every 3-4 weeks for 8 courses in the absence of disease progression or unacceptable toxicity. Patients with Philadelphia chromosome-positive disease also receive oral imatinib mesylate daily beginning at diagnosis.

Patients who complete 8 courses of chemotherapy and are not candidates for hematopoietic stem cell transplantation receive maintenance therapy off study.

Blood samples are collected at baseline and periodically during study for pharmacokinetics and neutralizing antibody assays.

After completion of study therapy, patients are followed up every 6 months.

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Group 1	Experimental	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	Drug: cyclophosphamide Drug: cytarabine Drug: dexamethasone Drug: doxorubicin hydrochloride Drug: imatinib mesylate Drug: methotrexate Drug: methylprednisolone Drug: pegaspargase Drug: vincristine sulfate

Interventions

Name	Type	Description	Arm Group Labels	Other Names
cyclophosphamide	Drug	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	Group 1

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Complete Response Rate After Course 1 of Pegaspargase When Administered in Combination With Hyper-CVAD Regimen	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.	After day 4 of treatment
Grade 3 and 4 Toxicity Associated With the Combination of Peg-Asparaginase and Hyper-CVAD Which Include: Allergic Reactions, Elevated Liver Enzymes, Hyperbilirubinemia, Hyperglycemia, Central Nervous System (CNS) Thrombosis, and Pancreatitis.		The assessment of safety will be based mainly on the frequency of adverse events

Secondary Outcomes

Measure	Description	Time Frame
2-year Progression-free Survival		After completion of 8 cycles
Proportion of Patients Who Achieve Complete Response or Partial Response After Courses 1 and 2		An interim analysis of safety is planned after the enrollment of 15 evaluable patients.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Patients must be newly diagnosed (untreated) with Acute Lymphoblastic Leukemia based on a bone marrow examination unless there is a contraindication to having the test performed. This includes precursor-B ALL, precursor-T ALL, and Philadelphia chromosome positive ALL. For reference, see criteria by Center for International Blood and Marrow Transplant Research (CIBMTR).> 20% blasts on a bone marrow aspirate OR If a bone marrow aspirate is not obtained, the diagnosis of acute leukemia can be established by a pathologic diagnosis of acute leukemia on a bone marrow biopsy OR A complete blood count documenting the presence of at least 10,000 white blood cells (WBC)/μl and at least 20% circulating blasts
Adults, 18 to 60 years of age.
Women of child bearing potential (WOCBP) must be willing to use adequate contraception to avoid pregnancy for the duration of study participation.
Eastern Cooperative Oncology Group (ECOG) performance status < 2
Adequate renal function defined as: Serum creatinine ≤ 2.0 x upper limit normal (ULN) for institution
Adequate hepatic function defined as:Total bilirubin ≤ 2.0 x ULN for institution Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.0 x ULN for institution
Patient must have the ability to understand and the willingness to sign a written informed consent document. The patient and/or the patient's legally authorized guardian must acknowledge consent for treatment as a human subject on this study.

Exclusion Criteria:

Mature B (Burkitt's) ALL will be excluded.
An active malignancy other than ALL (with the exception of basal and/or squamous cell skin cancers and curatively treated carcinoma of the cervix) within 5 past years of study entry.
Documented central nervous system (CNS) involvement with leukemia will be excluded. A diagnostic lumbar puncture will not be part of screening procedures.
Severe pulmonary, renal, or hepatic disease not related to the patient's ALL will be excluded.
Cardiac dysfunction as defined by:Myocardial infarction within the last 6 months of study entry, or Reduced left ventricular function with an ejection fraction ≤50% as measured by Multigated Acquisition (MUGA) scan or echocardiogram at study entry, Unstable angina, Unstable cardiac arrhythmias, New York Heart Association (NYHA) Class III or IV heart failure, Electrocardiographic evidence of acute ischemia or active conduction system abnormalities
Known or suspected human immunodeficiency virus (HIV)-positive patients are excluded from the study because of possible risk of lethal infection when treated with marrow suppressive therapy.
Any concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, etc.) or psychiatric illness that could, in the investigator's opinion, potentially interfere with the completion of treatment according to this protocol.
Patients who have had chemotherapy or radiotherapy for ALL prior to entering the study will be excluded. Hydroxyurea and one dose of intravenous vincristine are allowed prior to registration for patient convenience. Prior steroid therapy is allowable, ≤5 days prior to the start of the regimen.
Patients may not have received any other investigational agents within the last 30 days.
WOCBP who are unwilling or unable to use an acceptable method of contraception for the entire study period. Pregnant or lactating women are excluded from this study because of possible risk to the fetus or infant. Women with a positive serum pregnancy test on enrollment or prior to study drug administration will be excluded.
Men whose sexual partners are WOCBP, who are unwilling or unable to use an acceptable contraceptive method to avoid pregnancy of his partner for the entire study period.

Contacts/Locations Module

Name	Affiliation	Role
Brandon Hayes-Lattin	OHSU Knight Cancer Institute	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
OHSU Knight Cancer Institute		Portland	Oregon	97239	United States

References Module

No data available

No data is available for this block.

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	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

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

Intervention Browse Module

Masking Info

Cytoxan, Neosar, CTX

Outcome data was not collected due to early termination of the study due to safety concerns.

Arm/Group Information

ID	Title	Description
BG000	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

Units	Counts
Participants	BG00011

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Categorical

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
<=18 years	BG0000
Between 18 and 65 years	BG00011
>=65 years	BG000

Age, Continuous

Mean

Full Range

years

Title

Denominators

Categories

Title	Measurements
	BG00042.9(22 to 60)

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG0005
Male	BG0006

Region of Enrollment

Number

participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00011

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Complete Response Rate After Course 1 of Pegaspargase When Administered in Combination With Hyper-CVAD Regimen

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 data for this study was not collected due to early termination of the study due to safety concerns. Only one subject completed the study.

Posted

After day 4 of treatment

ID	Title	Description
OG000	Group 1	Cy D1- 3: 300 m g/m2 IV- 6 doses, mesna 600 mg/ m2 /day continuous IV D 1-3, ARAC D 2 & 3: 3g/m2 IV q12 X 4, Dex D1-4; 11-14: 40 mg daily, doxorubicin hydrochloride D4: 50 mg/m2 IV, imatinib mesylate 600 mg/day, MTX D1: 1g/ m2 200 mg/ m2 load IV plus 800 mg/ m2, methylprednisolone D 1-3: 50mg IV BID, pegaspargase D3/D4: 2,500 IU/ m2 IV, vincristine sulfate D4 & 11: 2 mg IV, Cy: D 1- 3: 300 m g/m2 IV 6 doses plus mesna 600 mg/ m2 /day, continuous infusion D 1-3. ARAC D 2 & 3: 3g/m2 IV q12 X 4, dex: D 1-4; 11-14: 40 mg daily, doxorubicin hydrochloride: D 4: 50 mg/m2 IV, imatinib mesylate: 600 mg/day, MTX: D 1: 1g/ m2 200 mg/ m2load IV plus 800 mg/ m2 IV, methylprednisolone: D 1-3: 50mg IV BID, pegaspargase: D 3/D4: 2,500 IU/ m2 IV, vincristine sulfate: D 4 & 11: 2 mg IV, pharmacological study: C1A: pre-dose between Days 1 to 4, C1A: D11 or 12., C1A: D18 or 19, C 1A: D25 or 26, C1A: D32 or 33 C1B: pre-dose between D1-3, C1B: D1 or 11 C1B: D17 or 18, C1B: D24 or 25 C1B: D31 or 32

Units	Counts
Participants	OG0000

Primary

Grade 3 and 4 Toxicity Associated With the Combination of Peg-Asparaginase and Hyper-CVAD Which Include: Allergic Reactions, Elevated Liver Enzymes, Hyperbilirubinemia, Hyperglycemia, Central Nervous System (CNS) Thrombosis, and Pancreatitis.

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.

Posted

The assessment of safety will be based mainly on the frequency of adverse events

ID	Title	Description
OG000	Group 1	Cy D1- 3: 300 m g/m2 IV- 6 doses, mesna 600 mg/ m2 /day continuous IV D 1-3, ARAC D 2 & 3: 3g/m2 IV q12 X 4, Dex D1-4; 11-14: 40 mg daily, doxorubicin hydrochloride D4: 50 mg/m2 IV, imatinib mesylate 600 mg/day, MTX D1: 1g/ m2 200 mg/ m2 load IV plus 800 mg/ m2, methylprednisolone D 1-3: 50mg IV BID, pegaspargase D3/D4: 2,500 IU/ m2 IV, vincristine sulfate D4 & 11: 2 mg IV, Cy: D 1- 3: 300 m g/m2 IV 6 doses plus mesna 600 mg/ m2 /day, continuous infusion D 1-3. ARAC D 2 & 3: 3g/m2 IV q12 X 4, dex: D 1-4; 11-14: 40 mg daily, doxorubicin hydrochloride: D 4: 50 mg/m2 IV, imatinib mesylate: 600 mg/day, MTX: D 1: 1g/ m2 200 mg/ m2load IV plus 800 mg/ m2 IV, methylprednisolone: D 1-3: 50mg IV BID, pegaspargase: D 3/D4: 2,500 IU/ m2 IV, vincristine sulfate: D 4 & 11: 2 mg IV, pharmacological study: C1A: pre-dose between Days 1 to 4, C1A: D11 or 12., C1A: D18 or 19, C 1A: D25 or 26, C1A: D32 or 33 C1B: pre-dose between D1-3, C1B: D1 or 11 C1B: D17 or 18, C1B: D24 or 25 C1B: D31 or 32

Units	Counts

Secondary

2-year Progression-free Survival

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.

Posted

After completion of 8 cycles

ID	Title	Description
OG000	Group 1	Cy D1- 3: 300 m g/m2 IV- 6 doses, mesna 600 mg/ m2 /day continuous IV D 1-3, ARAC D 2 & 3: 3g/m2 IV q12 X 4, Dex D1-4; 11-14: 40 mg daily, doxorubicin hydrochloride D4: 50 mg/m2 IV, imatinib mesylate 600 mg/day, MTX D1: 1g/ m2 200 mg/ m2 load IV plus 800 mg/ m2, methylprednisolone D 1-3: 50mg IV BID, pegaspargase D3/D4: 2,500 IU/ m2 IV, vincristine sulfate D4 & 11: 2 mg IV, Cy: D 1- 3: 300 m g/m2 IV 6 doses plus mesna 600 mg/ m2 /day, continuous infusion D 1-3. ARAC D 2 & 3: 3g/m2 IV q12 X 4, dex: D 1-4; 11-14: 40 mg daily, doxorubicin hydrochloride: D 4: 50 mg/m2 IV, imatinib mesylate: 600 mg/day, MTX: D 1: 1g/ m2 200 mg/ m2load IV plus 800 mg/ m2 IV, methylprednisolone: D 1-3: 50mg IV BID, pegaspargase: D 3/D4: 2,500 IU/ m2 IV, vincristine sulfate: D 4 & 11: 2 mg IV, pharmacological study: C1A: pre-dose between Days 1 to 4, C1A: D11 or 12., C1A: D18 or 19, C 1A: D25 or 26, C1A: D32 or 33 C1B: pre-dose between D1-3, C1B: D1 or 11 C1B: D17 or 18, C1B: D24 or 25 C1B: D31 or 32

Units	Counts
Participants

Secondary

Proportion of Patients Who Achieve Complete Response or Partial Response After Courses 1 and 2

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.

Posted

An interim analysis of safety is planned after the enrollment of 15 evaluable patients.

ID	Title	Description
OG000	Group 1	Cy D1- 3: 300 m g/m2 IV- 6 doses, mesna 600 mg/ m2 /day continuous IV D 1-3, ARAC D 2 & 3: 3g/m2 IV q12 X 4, Dex D1-4; 11-14: 40 mg daily, doxorubicin hydrochloride D4: 50 mg/m2 IV, imatinib mesylate 600 mg/day, MTX D1: 1g/ m2 200 mg/ m2 load IV plus 800 mg/ m2, methylprednisolone D 1-3: 50mg IV BID, pegaspargase D3/D4: 2,500 IU/ m2 IV, vincristine sulfate D4 & 11: 2 mg IV, Cy: D 1- 3: 300 m g/m2 IV 6 doses plus mesna 600 mg/ m2 /day, continuous infusion D 1-3. ARAC D 2 & 3: 3g/m2 IV q12 X 4, dex: D 1-4; 11-14: 40 mg daily, doxorubicin hydrochloride: D 4: 50 mg/m2 IV, imatinib mesylate: 600 mg/day, MTX: D 1: 1g/ m2 200 mg/ m2load IV plus 800 mg/ m2 IV, methylprednisolone: D 1-3: 50mg IV BID, pegaspargase: D 3/D4: 2,500 IU/ m2 IV, vincristine sulfate: D 4 & 11: 2 mg IV, pharmacological study: C1A: pre-dose between Days 1 to 4, C1A: D11 or 12., C1A: D18 or 19, C 1A: D25 or 26, C1A: D32 or 33 C1B: pre-dose between D1-3, C1B: D1 or 11 C1B: D17 or 18, C1B: D24 or 25 C1B: D31 or 32

Units	Counts
Participants

Secondary

Overall Survival

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.

Posted

At least every 6 months until death.

ID	Title	Description
OG000	Group 1	Cy D1- 3: 300 m g/m2 IV- 6 doses, mesna 600 mg/ m2 /day continuous IV D 1-3, ARAC D 2 & 3: 3g/m2 IV q12 X 4, Dex D1-4; 11-14: 40 mg daily, doxorubicin hydrochloride D4: 50 mg/m2 IV, imatinib mesylate 600 mg/day, MTX D1: 1g/ m2 200 mg/ m2 load IV plus 800 mg/ m2, methylprednisolone D 1-3: 50mg IV BID, pegaspargase D3/D4: 2,500 IU/ m2 IV, vincristine sulfate D4 & 11: 2 mg IV, Cy: D 1- 3: 300 m g/m2 IV 6 doses plus mesna 600 mg/ m2 /day, continuous infusion D 1-3. ARAC D 2 & 3: 3g/m2 IV q12 X 4, dex: D 1-4; 11-14: 40 mg daily, doxorubicin hydrochloride: D 4: 50 mg/m2 IV, imatinib mesylate: 600 mg/day, MTX: D 1: 1g/ m2 200 mg/ m2load IV plus 800 mg/ m2 IV, methylprednisolone: D 1-3: 50mg IV BID, pegaspargase: D 3/D4: 2,500 IU/ m2 IV, vincristine sulfate: D 4 & 11: 2 mg IV, pharmacological study: C1A: pre-dose between Days 1 to 4, C1A: D11 or 12., C1A: D18 or 19, C 1A: D25 or 26, C1A: D32 or 33 C1B: pre-dose between D1-3, C1B: D1 or 11 C1B: D17 or 18, C1B: D24 or 25 C1B: D31 or 32

Units	Counts
Participants

Secondary

Rate of Minimal Residual Disease

Cycle 1A: Days 1 through 14 Cycle 1B: Days 1 through 8, after the first 14 days of cycle 1A

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.

Posted

End of cycles 1A and 1B

ID	Title	Description
OG000	Group 1	Cy D1- 3: 300 m g/m2 IV- 6 doses, mesna 600 mg/ m2 /day continuous IV D 1-3, ARAC D 2 & 3: 3g/m2 IV q12 X 4, Dex D1-4; 11-14: 40 mg daily, doxorubicin hydrochloride D4: 50 mg/m2 IV, imatinib mesylate 600 mg/day, MTX D1: 1g/ m2 200 mg/ m2 load IV plus 800 mg/ m2, methylprednisolone D 1-3: 50mg IV BID, pegaspargase D3/D4: 2,500 IU/ m2 IV, vincristine sulfate D4 & 11: 2 mg IV, Cy: D 1- 3: 300 m g/m2 IV 6 doses plus mesna 600 mg/ m2 /day, continuous infusion D 1-3. ARAC D 2 & 3: 3g/m2 IV q12 X 4, dex: D 1-4; 11-14: 40 mg daily, doxorubicin hydrochloride: D 4: 50 mg/m2 IV, imatinib mesylate: 600 mg/day, MTX: D 1: 1g/ m2 200 mg/ m2load IV plus 800 mg/ m2 IV, methylprednisolone: D 1-3: 50mg IV BID, pegaspargase: D 3/D4: 2,500 IU/ m2 IV, vincristine sulfate: D 4 & 11: 2 mg IV, pharmacological study: C1A: pre-dose between Days 1 to 4, C1A: D11 or 12., C1A: D18 or 19, C 1A: D25 or 26, C1A: D32 or 33 C1B: pre-dose between D1-3, C1B: D1 or 11 C1B: D17 or 18, C1B: D24 or 25 C1B: D31 or 32

Units	Counts
Participants

Secondary

Half-life of Pegaspargase

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.

Posted

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.

ID	Title	Description
OG000	Group 1	Cy D1- 3: 300 m g/m2 IV- 6 doses, mesna 600 mg/ m2 /day continuous IV D 1-3, ARAC D 2 & 3: 3g/m2 IV q12 X 4, Dex D1-4; 11-14: 40 mg daily, doxorubicin hydrochloride D4: 50 mg/m2 IV, imatinib mesylate 600 mg/day, MTX D1: 1g/ m2 200 mg/ m2 load IV plus 800 mg/ m2, methylprednisolone D 1-3: 50mg IV BID, pegaspargase D3/D4: 2,500 IU/ m2 IV, vincristine sulfate D4 & 11: 2 mg IV, Cy: D 1- 3: 300 m g/m2 IV 6 doses plus mesna 600 mg/ m2 /day, continuous infusion D 1-3. ARAC D 2 & 3: 3g/m2 IV q12 X 4, dex: D 1-4; 11-14: 40 mg daily, doxorubicin hydrochloride: D 4: 50 mg/m2 IV, imatinib mesylate: 600 mg/day, MTX: D 1: 1g/ m2 200 mg/ m2load IV plus 800 mg/ m2 IV, methylprednisolone: D 1-3: 50mg IV BID, pegaspargase: D 3/D4: 2,500 IU/ m2 IV, vincristine sulfate: D 4 & 11: 2 mg IV, pharmacological study: C1A: pre-dose between Days 1 to 4, C1A: D11 or 12., C1A: D18 or 19, C 1A: D25 or 26, C1A: D32 or 33 C1B: pre-dose between D1-3, C1B: D1 or 11 C1B: D17 or 18, C1B: D24 or 25 C1B: D31 or 32

Units	Counts
Participants

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Group 1	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			9	11	0	11

Serious Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Bacillus species sepsis with encephalitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected11 at risk
Chest pain	Cardiac disorders	Systematic Assessment	EG0001 events1 affected11 at risk
neutropenic fever	Blood and lymphatic system disorders	Systematic Assessment	EG0007 events4 affected11 at risk
Cardiac Arrest	Cardiac disorders	Systematic Assessment	EG0001 events1 affected11 at risk
Abdominal pain	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected11 at risk
Septic shock	Infections and infestations	Systematic Assessment	EG0002 events2 affected11 at risk
Pulmonary embolism	Vascular disorders	Systematic Assessment	EG0001 events1 affected11 at risk
Death	General disorders	Systematic Assessment	EG0001 events1 affected11 at risk
hypokalemia, hyponatremia	Blood and lymphatic system disorders	Systematic Assessment	EG0002 events1 affected11 at risk
fungemia, staph bacteremia	Infections and infestations	Systematic Assessment	EG0001 events1 affected11 at risk
gnr bacteremia	Infections and infestations	Systematic Assessment	EG0001 events1 affected11 at risk
anaphylaxis	Immune system disorders	Systematic Assessment	EG0001 events1 affected11 at risk
acute epiglottitis	Infections and infestations	Systematic Assessment	EG0001 events1 affected11 at risk
klebsiella bacteremia	Infections and infestations	Systematic Assessment	EG0001 events1 affected11 at risk
gastoenteritis	Gastrointestinal disorders	Systematic Assessment	EG0001 events1 affected11 at risk
pneumonia (streptoccocus bacteremia)	Infections and infestations	Systematic Assessment	EG0001 events1 affected11 at risk
lung infection (fungal)	Infections and infestations	Systematic Assessment	EG0001 events1 affected11 at risk
alpha-hemolytic streptococcal bacteremia	Infections and infestations	Systematic Assessment	EG0001 events1 affected11 at risk

Study terminated early due to safety concerns. Only one subject completed the study.

Certain Agreements

ID	Term
D007938	Leukemia
D054218	Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Ancestor Terms

ID	Term
D009370	Neoplasms by Histologic Type
D009369	Neoplasms
D006402	Hematologic Diseases
D006425	Hemic and Lymphatic Diseases
D054198	Precursor Cell Lymphoblastic Leukemia-Lymphoma
D007945	Leukemia, Lymphoid
D008232	Lymphoproliferative Disorders
D008206	Lymphatic Diseases
D007160	Immunoproliferative Disorders
D007154	Immune System Diseases

ID	Term
D003520	Cyclophosphamide
D003561	Cytarabine
D003907	Dexamethasone
D002123	Calcium Dobesilate
D004317	Doxorubicin
D000068877	Imatinib Mesylate
D008727	Methotrexate
D008775	Methylprednisolone
D000077555	Methylprednisolone Acetate
D008776	Methylprednisolone Hemisuccinate
C042705	pegaspargase
D014750	Vincristine

Ancestor Terms

ID	Term
D010752	Phosphoramide Mustards
D009588	Nitrogen Mustard Compounds
D009150	Mustard Compounds
D006846	Hydrocarbons, Halogenated
D006838	Hydrocarbons
D009930	Organic Chemicals
D063088	Phosphoramides
D009943	Organophosphorus Compounds
D003562	Cytidine
D011741	Pyrimidine Nucleosides
D011743	Pyrimidines
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D001087	Arabinonucleosides
D009705	Nucleosides
D009706	Nucleic Acids, Nucleotides, and Nucleosides
D011246	Pregnadienetriols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D013259	Steroids, Fluorinated
D001557	Benzenesulfonates
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D001190	Arylsulfonates
D017739	Arylsulfonic Acids
D013451	Sulfonic Acids
D013456	Sulfur Acids
D013457	Sulfur Compounds
D003630	Daunorubicin
D018943	Anthracyclines
D009279	Naphthacenes
D011084	Polycyclic Aromatic Hydrocarbons
D000617	Aminoglycosides
D006027	Glycosides
D002241	Carbohydrates
D001549	Benzamides
D000577	Amides
D001565	Benzoates
D000146	Acids, Carbocyclic
D002264	Carboxylic Acids
D010879	Piperazines
D000630	Aminopterin
D011622	Pterins
D011621	Pteridines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D011239	Prednisolone
D014748	Vinca Alkaloids
D046948	Secologanin Tryptamine Alkaloids
D026121	Indole Alkaloids
D000470	Alkaloids
D007211	Indoles
D054836	Indolizidines
D007212	Indolizines