Pegaspargase and Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
Information source: OHSU Knight Cancer Institute
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Leukemia
Intervention: cyclophosphamide (Drug); cytarabine (Drug); dexamethasone (Drug); doxorubicin hydrochloride (Drug); imatinib mesylate (Drug); methotrexate (Drug); methylprednisolone (Drug); pegaspargase (Drug); vincristine sulfate (Drug)
Phase: Phase 2
Status: Terminated
Sponsored by: OHSU Knight Cancer Institute Official(s) and/or principal investigator(s): Brandon Hayes-Lattin, Principal Investigator, Affiliation: OHSU Knight Cancer Institute
Summary
RATIONALE: Drugs used in chemotherapy work in different ways to stop the growth of cancer
cells, either by killing the cells or by stopping them from dividing. Giving more than one
drug (combination chemotherapy) may kill more cancer cells.
PURPOSE: This phase II trial is studying the side effects of giving pegaspargase together
with combination chemotherapy and to see how well it works in treating patients with newly
diagnosed acute lymphoblastic leukemia.
Clinical Details
Official title: Phase II Trial of the Addition of PEG-Asparaginase to the Hyper-CVAD Regimen in Adult Newly-Diagnosed Acute Lymphoblastic Leukemia
Study design: Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Complete Response Rate After Course 1 of Pegaspargase When Administered in Combination With Hyper-CVAD RegimenGrade 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.
Secondary outcome: 2-year Progression-free SurvivalProportion of Patients Who Achieve Complete Response or Partial Response After Courses 1 and 2 Overall Survival Rate of Minimal Residual Disease Half-life of Pegaspargase
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 60 Years.
Gender(s): Both.
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.
Locations and Contacts
OHSU Knight Cancer Institute, Portland, Oregon 97239, United States
Additional Information
Starting date: June 2009
Last updated: February 12, 2015
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