A PHASE III TRIAL TO EVALUATE THE EFFICACY OF THE ADDITION OF INOTUZUMAB OZOGAMICIN (A CONJUGATED ANTI-CD22MONOCLONAL ANTIBODY) TO FRONTLINE THERAPY IN YOUNG ADULTS (AGES 18-39 YEARS) WITH NEWLY DIAGNOSED PRECURSOR B-CELL ALL

This partially randomized phase III trial studies the side effects of inotuzumab ozogamicin
and how well it works when given with frontline chemotherapy in treating patients with newly
diagnosed B acute lymphoblastic leukemia. Monoclonal antibodies, such as inotuzumab
ozogamicin, may block cancer growth in different ways by targeting certain cells. Drugs used
in chemotherapy work in different ways to stop the growth of tumor cells, either by killing
the cells, by stopping them from dividing, or by stopping them from spreading. Giving
inotuzumab ozogamicin with chemotherapy may work better in treating young adults with B acute
lymphoblastic leukemia.

Inclusion Criteria:

REGISTRATION ELIGIBILITY CRITERIA (STEP 1)

- Newly diagnosed patients with CD-22 positive B-cell acute lymphoblastic leukemia (WHO
criteria) are eligible. Patients with Burkitt type ALL are NOT eligible

- Patients who have BCR-ABL fusion transcript determined by fluorescence in situ
hybridization (FISH) or real time-polymerase chain reaction (RT-PCR) or
t(9;22)(q34;q11) by cytogenetics are not eligible and should be considered for
enrollment on studies that incorporate imatinib during induction; please note: flow
cytometry is to be performed at the local reference lab and must include assessment of
CD20 and CD22 positivity, as well as CD29 and CD22 anti-positivity

- No prior therapy except for limited treatment (< 7 days) with corticosteroids or
hydroxyurea and a single dose of intrathecal cytarabine

- No prior therapy for acute leukemia except emergency therapy (corticosteroids or
hydroxyurea) for blast cell crisis, superior vena cava syndrome, or renal failure due
to leukemic infiltration of the kidneys; when indicated, leukapheresis or exchange
transfusion is recommended to reduce the WBC

- Single-dose intrathecal cytarabine is allowed prior to registration or prior to
initiation of systematic therapy for patient convenience; systemic chemotherapy must
begin within 72 hours of this intrathecal therapy

- Patients receiving prior steroid therapy are eligible for study; the dose and duration
of previous steroid therapy should be carefully documented on case report forms

- Not pregnant and not nursing; for women of childbearing potential only, a negative
urine or serum pregnancy test done =< 7 days prior to registration is required

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Patients with down syndrome are excluded from this study

- Aspartate aminotransferase (AST), alanine aminotransferase (ALT) =< 3 x upper limit of
normal (ULN), unless suspected leukemic involvement of the liver

- Direct bilirubin =< 3 x upper limit of normal (ULN), unless suspected leukemic
involvement of the liver

- Calculated (calc.) creatinine clearance >= 50 mL/min by Cockcroft-Gault

RANDOMIZATION ELIGIBILITY CRITERIA (STEP 2)

- Completion of remission induction therapy

- Patients with M2 marrow or better are eligible; patients with M3 or M4 marrow (greater
than 25% lymphoblasts) will not be eligible to be randomized

- Rating: M0, M1; Blast Cells (%): 0-5.0

- Rating: M2; Blast Cells (%): 5.1-25.0

- Rating: M3; Blast Cells (%): > 25-50

- Rating: M4; Blast Cells (%): > 50.0

- The term "blast cell" includes any cell that cannot be classified as a more
mature normal element, and includes "leukemic cells," pathologic lymphocytes, and
stem cells

- No ascites, effusions or significant edema

- Absolute neutrophil count (ANC) >= 1,000/mm^3

- Platelet count >= 100,000/mm^3

- Total bilirubin =< 1.5 x upper limit of normal (ULN), except for patients with known
Gilbert's syndrome

- Aspartate aminotransferase (AST) =< 8 x upper limit of normal (ULN)

- Completion of first 12 weeks (12+ weeks) of maintenance therapy (Course V)

- Patient has at least 24 weeks (24+ weeks) remaining before end of maintenance therapy
(Course V)

- Patient is in complete continuous first remission at entry into A041501-HO1

- Patient is receiving oral anti-metabolite chemotherapy during the maintenance phase of
therapy; treatment plan must call for the following doses of antimetabolites: 6MP 75
mg/m2/day orally; methotrexate (MTX) 20 mg/m2/week orally (modification of 6 MP or MTX
dosing based on laboratory or clinical parameters is acceptable)

- Patient is able and willing to use the Medication Event Monitoring System (MEMS)
TrackCap (e.g. not using a pillbox)