Clinical trial NCT01005914
Conditions: Leukemia
Keywords: adults Philadelphia chromosome precursor ALL, T-cell ALL untreated ALL
Sponsor: OHSU Knight Cancer Institute
Start date: 2009-06-01; Completion date: 2014-05-01
Enrollment: 11 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief 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.

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.

Arms: arm 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
Interventions: intervention 1: cyclophosphamide intervention 2: cytarabine intervention 3: dexamethasone intervention 4: doxorubicin hydrochloride intervention 5: imatinib mesylate intervention 6: methotrexate intervention 7: methylprednisolone intervention 8: pegaspargase intervention 9: vincristine sulfate
Intervention descriptions: intervention 1: 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 intervention 2: Day 2 \& 3: 3g/m2 IV over 2 hours q12 X 4 intervention 3: Day 1-4; 11-14: 40 mg daily intervention 4: Day 4: 50 mg/m2 IV over 2 hours intervention 5: 600 mg/day intervention 6: Day 1: 1g/ m2 (200 mg/ m2load IV over 2 hours plus 800 mg/ m2 over 22 hours as an infusion intervention 7: Day 1-3: 50mg IV BID intervention 8: Day 3/Day4: 2,500 IU/ m2 IV intervention 9: Day 4 \& 11: 2 mg IV

Protocol documents: