Clinical Trial: Leukemia and Lymphoma, Cancer

A041501 Leukemia

Full Name

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

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.

Eligibility

Inclusion Criteria
  • 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)
Doctor(s) Running This Study