Pegaspargase and Combination Chemotherapy in Treating Patients With Newly Diagnosed Acute Lymphoblastic Leukemia
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.
Drug: doxorubicin hydrochloride
Drug: imatinib mesylate
Drug: vincristine sulfate
Other: pharmacological study
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Trial of the Addition of PEG-Asparaginase to the Hyper-CVAD Regimen in Adult Newly-Diagnosed Acute Lymphoblastic Leukemia|
- Complete response rate after course 1 of pegaspargase when administered in combination with hyper-CVAD regimen [ Time Frame: After day 4 of treatment ] [ Designated as safety issue: No ]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.
- Grade 3 and 4 toxicity associated with the combination of Peg-Asparaginase and hyper-CVAD which include: allergic reactions, elevated liver enzymes, hyperbilirubinemia, hyperglycemia, CNS thrombosis, and pancreatitis. [ Time Frame: The assessment of safety will be based mainly on the frequency of adverse events ] [ Designated as safety issue: Yes ]
- 2-year progression-free survival [ Time Frame: After completion of 8 cycles ] [ Designated as safety issue: No ]
- Proportion of patients who achieve complete response or partial response after courses 1 and 2 [ Time Frame: An interim analysis of safety is planned after the enrollment of 15 evaluable patients. ] [ Designated as safety issue: No ]
- Overall survival [ Time Frame: At least every 6 months until death. ] [ Designated as safety issue: No ]
- Rate of minimal residual disease [ Time Frame: End of cycles 1A and 1B ] [ Designated as safety issue: No ]Cycle 1A: Days 1 through 14 Cycle 1B: Days 1 through 8, after the first 14 days of cycle 1A
- Half-life of pegaspargase [ Time Frame: 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. ] [ Designated as safety issue: No ]
|Study Start Date:||June 2009|
|Primary Completion Date:||March 2013 (Final data collection date for primary outcome measure)|
Experimental: 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
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 1-3Drug: cytarabine
Day 2 & 3: 3g/m2 IV over 2 hours q12 X 4Drug: dexamethasone
Day 1-4; 11-14: 40 mg dailyDrug: doxorubicin hydrochloride
Day 4: 50 mg/m2 IV over 2 hoursDrug: imatinib mesylate
Other Name: Gleevec, GlivecDrug: methotrexate
Day 1: 1g/ m2 (200 mg/ m2load IV over 2 hours plus 800 mg/ m2 over 22 hours as an infusionDrug: methylprednisolone
Day 1-3: 50mg IV BIDDrug: pegaspargase
Day 3/Day4: 2,500 IU/ m2 IVDrug: vincristine sulfate
Day 4 & 11: 2 mg IVOther: pharmacological study
Cycle 1A: pre-dose between Days 1 to 4 Cycle 1A: Days 11 or 12 (+/- 2 days) Cycle 1A: Days 18 or 19 (+/- 2 days) Cycle 1A: Days 25 or 26 (+/- 2 days) Cycle 1A: Days 32 or 33 (+/- 2 days)* Cycle 1B: pre-dose between Days 1 to 3 Cycle 1B: Days 1o or 11 (+/- 2 days) Cycle 1B: Days 17 or 18 (+/- 2 days) Cycle 1B: Days 24 or 25 (+/- 2 days) Cycle 1B: Days 31 or 32 (+/- 2 days)**
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01005914
|United States, Oregon|
|OHSU Knight Cancer Institute|
|Portland, Oregon, United States, 97239|
|Principal Investigator:||Brandon Hayes-Lattin||OHSU Knight Cancer Institute|