Clinical trial NCT00866307
Conditions: Acute Lymphoblastic Leukemia Adult B Acute Lymphoblastic Leukemia Childhood B Acute Lymphoblastic Leukemia
Sponsor: Children's Oncology Group
Start date: 2009-02-23; Completion date: 2021-03-31
Enrollment: 104 participants; Allocation: NON_RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This pilot clinical trial studies the side effects of pegaspargase when given together with combination chemotherapy in treating patients with newly diagnosed high-risk acute lymphoblastic leukemia. Pegaspargase may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving more than one drug (combination chemotherapy) together with pegaspargase may kill more cancer cells.

Detailed description:
PRIMARY OBJECTIVES:

I. To demonstrate that biweekly intravenous (IV) pegaspargase beginning with Consolidation and ending with completion of delayed intensification (DI) in combination with hemi-augmented BFM therapy (hABFM) is feasible and safe in children with high risk (HR) acute lymphoblastic leukemia (ALL).

OUTLINE: Patients are stratified according to risk assignment (high-risk \[HR\]-average \[day 29 minimal residual disease (MRD) \< 0.01%\] vs HR-high \[MRD \>= 0.01%, presence of central nervous system \[CNS\]3 leukemia, testicular disease, myeloid/mixed lineage leukemia \[MLL\] rearrangement, hypodiploidy, or steroid therapy within the past month\]). Patients are assigned to 1 of 2 treatment groups.\*

(Note: \*Amendment 2 \[4-22-2011\] requires changes in the regimens. See the changes below, after Maintenance therapy.)

INDUCTION THERAPY: All patients receive cytarabine intrathecally (IT) on day 1; vincristine sulfate IV on days 1, 8, 15, and 22; prednisone IV or orally (PO) twice daily (BID) on days 1-28; daunorubicin hydrochloride IV over 15 minutes on days 1, 8, 15, and 22; methotrexate IT on days 8 and 29\*; and pegaspargase IV over 1-2 hours on day 4.

(Note: \*Patients with CNS3 disease \[white blood cells \[(WBC)\] \>= 5/uL and positive for blasts on cytospin\] also receive methotrexate IT on days 15 and 22.)

CONSOLIDATION THERAPY (begins on day 36 of induction therapy):

GROUP A (HR-AVERAGE): Patients receive cyclophosphamide IV over 1 hour on days 1 and 29; cytarabine IV over 15 minutes or subcutaneously (SC) on days 1-4, 8-11, 29-32, and 36-39; mercaptopurine PO once daily (QD) on days 1-14 and 29-42; vincristine sulfate IV on days 15, 22, 43, and 50; methotrexate IT on days 1, 8, 15\*, and 22\*; and pegaspargase IV over 1-2 hours on days 15 and 43.

GROUP B (HR-HIGH): Patients receive cyclophosphamide, cytarabine, mercaptopurine, vincristine sulfate, and methotrexate as in Group A. Beginning on day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks. Patients with CNS3 disease undergo cranial radiotherapy QD for 10 days and patients with testicular disease undergo testicular radiotherapy QD for 12 days, beginning on day 1 of consolidation.

(Note: \*Patients with CNS3 disease \[WBC \>= 5/uL and positive for blasts on cytospin\] do not receive methotrexate IT on days 15 and 22.)

Interim maintenance (IM) therapy (begins on day 57 of consolidation):

GROUP A: Patients receive vincristine sulfate IV on days 1, 11, 21, 31, and 41; methotrexate IV over 10-15 minutes on days 1, 11, 21, 31, and 41; methotrexate IT on days 1 and 31; and pegaspargase IV over 1-2 hours on days 2 and 22.

GROUP B: Patients receive vincristine sulfate and methotrexate as in Group A. Beginning on day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks.

DI therapy (begins on day 57 of IM):

GROUP A: Patients receive vincristine sulfate IV on days 1, 8, 15, 43, and 50; dexamethasone IV or PO BID on days 1-7 and 15-21; doxorubicin hydrochloride IV over 15 minutes on days 1, 8, and 15; cyclophosphamide IV over 1 hour on day 29; cytarabine IV over 15 minutes or SC on days 29-32 and 36-39; thioguanine PO on days 29-42; methotrexate IT on days 1, 29, and 36; and pegaspargase IV over 1-2 hours on days 4 and 43.

GROUP B: Patients receive vincristine sulfate, dexamethasone, doxorubicin hydrochloride, cyclophosphamide, cytarabine, thioguanine, and methotrexate as in Group A. Beginning on day 1, patients also receive pegaspargase IV over 1-2 hours every 2 weeks.

MAINTENANCE THERAPY (MT; begins on day 57 of DI): All patients receive vincristine sulfate IV on days 1, 29, and 57; prednisone PO BID on days 1-5, 29-33, and 57-61; mercaptopurine PO on days 1-84; methotrexate IT on day 1; and methotrexate PO BID on days 8, 15, 22, 29\*, 36, 43, 50, 57, 64, 71, and 78.

In both groups, MT repeats every 12 weeks until total duration of therapy is 2 years from the start of IM for female patients and 3 years from the start of IM for male patients. Patients in Group B who did not undergo radiotherapy to the brain during consolidation therapy undergo prophylactic cranial radiotherapy (CR) daily for 8 days.

(\[Note: \*Patients in Group A also receive methotrexate IT on day 29 of courses 1-4 \[no oral methotrexate\]).

REVISED MT (RMT): The regimen is the same as standard MT, but 2 of the doses of IT methotrexate are omitted (day 29 of courses 3 and 4).

Arms: arm 1: See Detailed Description. arm 2: See Detailed Description.
Interventions: intervention 1: Cyclophosphamide intervention 2: Cytarabine intervention 3: Daunorubicin Hydrochloride intervention 4: Dexamethasone intervention 5: Doxorubicin Hydrochloride intervention 6: Laboratory Biomarker Analysis intervention 7: Mercaptopurine intervention 8: Methotrexate intervention 9: Pegaspargase intervention 10: Prednisone intervention 11: Prophylactic Cranial Irradiation intervention 12: Thioguanine intervention 13: Vincristine Sulfate
Intervention descriptions: intervention 1: Given IV intervention 2: Given IT and IV or SC intervention 3: Given IV intervention 4: Given IV intervention 5: Given IV intervention 6: Correlative studies intervention 7: Given PO intervention 8: Given IT and PO intervention 9: Given IV intervention 10: Given IV or PO intervention 11: Undergo radiation intervention 12: Given PO intervention 13: Given IV

Protocol documents: