Title
A Phase III Trial to Evaluate the Efficacy of the Addition of Inotuzumab Ozogamicin (a Conjugated Anti-CD22 Monoclonal Antibody) to Frontline Therapy in Young Adults (Ages 18-39 Years) With Newly Diagnosed Precursor B-Cell ALL

Description
A Phase III Trial to Evaluate the Efficacy of the Addition of Inotuzumab Ozogamicin (a Conjugated Anti-CD22 Monoclonal Antibody) to Frontline Therapy in Young Adults (Ages 18-39 Years) With Newly Diagnosed Precursor B-Cell ALL

Objective
EFS [ Time Frame: Time from induction response to the time of progressive-disease, secondary malignancy, or death, assessed up to 3 years ] Will be compared using log-rank tests. EFS curves will be constructed using the Kaplan-Meier product limit method, and additional analyses will be done using the Cox proportional hazards model. The corresponding hazard ratio, 2- and 3-year EFS estimates will be assessed, and EFS medians along with their 95% confidence intervals for the two treatment arms.

Treatment

Drug: Allopurino

Drug: Cytarabine

Drug: Daunorubicin Hydrochloride

Drug: Vincristine Sulfate

Drug: Dexamethasone

Drug: Pegylated L-Asparaginase

Drug: Methotrexate

Procedure: Bone Marrow Aspiration and Biopsy

Drug: Cyclophosphamide

Drug: Mercaptopurine

Biological: Rituximab

Drug: Doxorubicin

Drug: Thioguanine

Biological: Inotuzumab Ozogamicin

Other: Laboratory Biomarker Analysis

Key Eligibility 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

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)

Applicable Disease Sites
Leukemia

Participating Institutions
UW Health Eastpark Medical Center; UW Health University Hospital