Protocol Summary

Protocol No.: OCR11124

Sponsor Protocol No.: AALL0932

Study Title
Treatment of Patients with Newly Diagnosed Standard Risk B - Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma (B-LLY)

Principal Investigator(s)
Slayton, William

Objective
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), giving the drugs in different doses, and giving the drugs in different combinations may kill more cancer cells.

This study is looking at different combinations of risk-adapted chemotherapy regimens and their side effects and comparing how well they work in treating younger patients with newly diagnosed standard-risk acute lymphoblastic leukemia or B-lineage lymphoblastic lymphoma that is found only in the tissue or organ where it began (localized).

Description
All patients receive induction therapy comprising intrathecal (IT) cytarabine on day 1; vincristine on days 1, 8, 15, and 22; dexamethasone on days 1-28; pegaspargase on day 4; and IT methotrexate on days 8 and 29.

AVERAGE-RISK:
Consolidation therapy (4 weeks): Vincristine on day 1; mercaptopurine PO on days 1-28; and IT methotrexate on days 1, 8, and 15.
Interim maintenance I therapy (8 weeks): Vincristine and methotrexate on days 1, 11, 21, 31, and 41 and IT methotrexate on day 31.
Delayed intensification therapy (8 weeks): Dexamethasone on days 1-7 and 15-21; Vincristine and doxorubicin on days 1, 8, and 15; pegaspargase on day 4; cyclophosphamide on day 29; thioguanine on days 29-42; cytarabine on days 29-32 and 36-39; and IT methotrexate on days 1 and 29.
Interim maintenance II therapy (8 weeks): Vincristine and methotrexate on days 1, 11, 21, 31, and 41 and IT methotrexate on days 1 and 31.
Maintenance therapy: Randomized to 1 of 4 maintenance therapy treatment arms.

Arm A:
Vincristine on days 1, 29, and 57; dexamethasone on days 1-5, 29-33, and 57-61; methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine on days 1-84; and IT methotrexate on day 1.

Arm B:
Vincristine on days 1, 29, and 57; dexamethasone on days 1-5, 29-33, and 57-61; higher-dose methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine on days 1-84; and IT methotrexate on day 1.

Arm C:
Vincristine on day 1; dexamethasone on days 1-5; methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine on days 1-84; and IT methotrexate on day 1.

Arm D:
Vincristine on day 1; dexamethasone on days 1-5; higher-dose methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine on days 1-84; and IT methotrexate on day 1.

In all arms, maintenance therapy courses repeat every 12 weeks for 2 years for girls and for 3 years for boys (timed from the start of interim maintenance I therapy).

LOW-RISK: Patients are randomized to 1 of 2 treatment arms.
Arm I (LR-M):
Consolidation therapy (19 weeks): Vincristine on days 15, 22, 78, and 85; methotrexate and IT methotrexate on days 8, 29, 50, 71, 92, and 113; leucovorin on days 9-10, 30-31, 51-52, 72-73, 93-94, and 114-115; dexamethasone on days 15-21 and 78-84; and mercaptopurine on days 1-133.
Maintenance therapy: Vincristine on days 1 and 8; dexamethasone on days 1-7; methotrexate on days 1, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, 99, and 106; and mercaptopurine on days 1-112. Courses repeat every 16 weeks. IT methotrexate on days 1 and 85 (courses 1 and 4), day 57 (courses 2 and 5), or day 29 (courses 3 and 6). Course 7 - vincristine on days 1 and 8; dexamethasone on days 1-7; methotrexate on days 1, 8, 15, 22, 29, 36, 43, 50, 57, and 64; and mercaptopurine on days 1-70. Treatment continues for 2 and 1/2 years (timed from the date of diagnosis).
Arm II (LR-C):
Consolidation therapy (4 weeks): Vincristine on day 1; mercaptopurine on days 1-28; and IT methotrexate on days 1, 8, and 15.
Interim maintenance I therapy (8 weeks): Vincristine and methotrexate on days 1, 11, 21, 31, and 41 and IT methotrexate on day 31.
Delayed-intensification therapy (8 weeks): Dexamethasone on days 1-7 and 15-21; vincristine and doxorubicin on days 1, 8, and 15; pegaspargase on day 4; cyclophosphamide on day 29; thioguanine on days 29-42; cytarabine on days 29-32 and 36-39; and IT methotrexate on days 1 and 29.
Interim maintenance II therapy (8 weeks): Vincristine and methotrexate on days 1, 11, 21, 31, and 41 and IT methotrexate on days 1 and 31.
Maintenance therapy: Vincristine on day 1; dexamethasone on days 1-5; methotrexate on days 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, and 78; mercaptopurine on days 1-84; and IT methotrexate on day 1. Courses repeat every 12 weeks for 2 years for girls and for 3 years for boys (timed from the start of interim maintenance I therapy).

Phase: Phase III

Age Group: Both

Scope: National

Treatment
Arms A, B, C, and D
- Vincristine, dexamethasone, methotrexate, and mercaptopurine.

Arm LR-C (Low risk
- Consolidation, interim maintenance I, delayed intensification, interim maintenance II, and maintenance therapy

Arm LR-M (Low risk
- Consolidation and maintenance therapy

Detailed Eligibility
Inclusion Criteria:
1. Ages 1 Year to 9 Years
2. B-ALL patients must be enrolled on AALL08B1 prior to treatment and enrollment on AALL0932
3. B-ALL patients must have an initial white blood cell count 4. Patients must have newly diagnosed National Cancer Institute (NCI) Standard Risk B-ALL or B-LLy Murphy stages I or II; patients with Down syndrome are also eligible
5. All patients and/or their parents or legal guardians must sign a written informed consent
6. All institutional, Food and Drug Administration (FDA), and National Cancer Institute (NCI) requirements for human studies must be met

Exclusion Criteria:
1. With the exception of steroid pretreatment (defined below) or the administration of intrathecal cytarabine, patients must not have received any prior cytotoxic chemotherapy for either the current diagnosis of B-ALL or B-LLy or for any cancer diagnosed prior to initiation of protocol therapy on AALL0932
- Patients receiving prior steroid therapy may be eligible for AALL0932
2. Patients with central nervous system 3 (CNS3) leukemia
- CNS status must be known prior to enrollment; (Note: the CNS status must be determined based on a sample obtained prior to administration of any systemic or intrathecal chemotherapy, except for steroid pretreatment); B-LLy patients with CNS3 disease are not eligible for this protocol or the COG HR ALL protocol; it is recommended that intrathecal cytarabine be administered at the time of the diagnostic lumbar puncture; this is usually done at the time of the diagnostic bone marrow or venous line placement to avoid a second lumbar puncture; this is allowed prior to registration; systemic chemotherapy must begin within 72 hours of the first dose of intrathecal therapy
3. B-ALL patients with testicular leukemia are not eligible for AALL0932
4. For B-LLy patients the following additional exclusion criteria apply:
- T-lymphoblastic lymphoma
- Morphologically unclassifiable lymphoma
- Absence of both B-cell and T-cell phenotype markers in a case submitted as lymphoblastic lymphoma
- CNS3-positive disease or testicular involvement
- M2 (5% - 25% blasts) or M3 (> 25% blasts) marrow
- Female patients who are pregnant are ineligible
- Lactating females are not eligible unless they have agreed not to breastfeed their infants
- Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained
- Sexually active patients of reproductive potential are not eligible unless they have agreed to use an effective contraceptive method for the duration of their study participation

Applicable Disease Sites
Leukemia
Pediatric (Childhood) Cancer

Participating Institutions
UF Gainesville

More Information:
View study listing on ClinicialTrials.gov
http://www.clinicaltrials.gov/ct2/show/
NCT01190930