Phase II Trial of the Addition of PEG-Asparaginase to the Hyper-CVAD Regimen in Adult Newly-Diagnosed Acute Lymphoblastic Leukemia
18 Years
60 Years
Both
Leukemia
Trial Information
Phase II Trial of the Addition of PEG-Asparaginase to the Hyper-CVAD Regimen in Adult Newly-Diagnosed Acute Lymphoblastic Leukemia
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of acute lymphoblastic leukemia (ALL), including any of the following:
- Precursor B-cell ALL
- No mature B-cell (Burkitt) ALL
- Precursor T-cell ALL
- Philadelphia chromosome-positive ALL
- Newly diagnosed disease based on bone marrow examination (unless there is a
contraindication to having the test performed), meeting 1 of the following criteria:
- > 20% blasts on bone marrow aspirate
- Pathologic confirmation by bone marrow biopsy
- WBC ≥ 10,000/μL with ≥ 20% circulating blasts
- No documented CNS involvement with leukemia
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Serum creatinine ≤ 2.0 times upper limit of normal (ULN)
- Total bilirubin ≤ 2.0 times ULN
- ALT and AST ≤ 2.0 times ULN
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No other active malignancy within the past 5 years except curatively treated basal
cell and/or squamous cell skin cancer or carcinoma of the cervix
- No severe pulmonary, renal, or hepatic disease not related to ALL
- No cardiac dysfunction, including any of the following:
- Myocardial infarction within the past 6 months
- Reduced left ventricular function with an ejection fraction ≤ 50% as measured by
MUGA scan or echocardiogram
- Unstable angina
- Unstable cardiac arrhythmias
- NYHA class III or IV heart failure
- Evidence of acute ischemia or active conduction system abnormalities by
electrocardiography
- No known or suspected HIV positivity
- No concurrent severe and/or uncontrolled medical condition (e.g., uncontrolled
diabetes, infection, hypertension) or psychiatric illness that, in the investigator's
opinion, could potentially interfere with the completion of study treatment
PRIOR CONCURRENT THERAPY:
- No prior chemotherapy or radiotherapy for ALL
- Hydroxyurea or one dose of IV vincristine sulfate allowed before study
registration for patient convenience
- Prior steroid therapy within the past 5 days allowed
- More than 30 days since prior investigational agents
- No other concurrent investigational or anticancer agents or therapies
Type of Study:
Interventional
Study Design:
Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Complete response rate after course 1 of pegaspargase when administered in combination with hyper-CVAD regimen
Outcome Description:
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 Time Frame:
After day 4 of treatment
Safety Issue:
No
Principal Investigator
Brandon Hayes-Lattin
Investigator Role:
Principal Investigator
Investigator Affiliation:
OHSU Knight Cancer Institute
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000642363
NCT ID:
NCT01005914
Start Date:
June 2009
Completion Date:
Related Keywords:
- Leukemia
- Philadelphia chromosome positive adult precursor acute lymphoblastic leukemia
- T-cell adult acute lymphoblastic leukemia
- untreated adult acute lymphoblastic leukemia
- Leukemia
- Leukemia, Lymphoid
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
Name | Location |
|---|---|
| OHSU Knight Cancer Institute | Portland, Oregon 97239 |
