Low-Intensity Chemotherapy and Blinatumomab in Treating Patients With Philadelphia Chromosome Negative Relapsed or Refractory Acute Lymphoblastic Leukemia
Condition: Philadelphia Chromosome Negative; Recurrent B Acute Lymphoblastic Leukemia; Refractory B Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Philadelphia Chromosome
Intervention: Blinatumomab; Cyclophosphamide; Cytarabine; Dexamethasone; Filgrastim; Laboratory Biomarker Analysis; Leucovorin Calcium; Mercaptopurine; Methotrexate; Pegfilgrastim; Rituximab; Vincristine Sulfate
Intervention description: Given IV; Given IV; Given IT or IV; PO or IV; Given SC; Correlative studies; Given IV; Given PO; Given IT or IV; Given SC; Given IV; Given IV
Intervention MeSH terms: Calcium, Dietary; Leucovorin; Folic Acid; Cytarabine; Dexamethasone; Dexamethasone acetate; Cyclophosphamide; Rituximab; Methotrexate; Vincristine; Mercaptopurine; Blinatumomab; Antineoplastic Agents, Immunological; Muromonab-CD3; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Lenograstim; Antibodies, Bispecific; BB 1101; Calcium; Levoleucovorin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial studies how well low-intensity chemotherapy and blinatumomab work in
      treating patients with Philadelphia chromosome negative acute lymphoblastic leukemia that has
      come back or does not respond to treatment. Drugs used in chemotherapy, such as
      dexamethasone, filgrastim, pegfilgrastim, cyclophosphamide, methotrexate, cytarabine and
      vincristine sulfate, 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.
      Immunotherapy with monoclonal antibodies, such as blinatumomab, may help the body's immune
      system attack the cancer, and may interfere with the ability of tumor cells to grow and
      spread. Giving low-intensity chemotherapy and blinatumomab may work better at treating acute
      lymphoblastic leukemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients with first or second relapsed/refractory B-cell acute lymphoblastic leukemia
             (ALL)

          -  Performance status =< 3 (Eastern Cooperative Oncology Group [ECOG] scale)

          -  Total serum bilirubin =< 2 x upper limit of normal (ULN), unless due to Gilbert's
             syndrome, hemolysis or the underlying leukemia approved by the principal investigator
             (PI)

          -  Alanine aminotransferase (ALT) =< 3 x ULN, unless due to the underlying leukemia
             approved by the PI

          -  Aspartate aminotransferase (AST) =< 3 x ULN unless due to the underlying leukemia
             approved by the PI

          -  Signed informed consent

          -  Women of childbearing potential (WOCBP) or male subjects with a partner who is WOCBP
             must agree to use contraception during the study, if sexually active

        Exclusion Criteria:

          -  Patients with Philadelphia chromosome (Ph)-positive ALL or Burkitt leukemia

          -  Active, uncontrolled central nervous system (CNS) leukemia involvement

          -  Active serious infection not controlled by oral or intravenous antibiotics

          -  Active secondary malignancy other than skin cancer (e.g., basal cell carcinoma or
             squamous cell carcinoma) that in the investigator's opinion will shorten survival to
             less than 1 year

          -  Known hepatitis B or C infection, or known seropositivity for human immunodeficiency
             virus (HIV)

          -  Active grade III-V cardiac failure as defined by the New York Heart Association
             criteria

          -  Patients with a cardiac ejection fraction (as measured by either multi-gated
             acquisition [MUGA] or echocardiogram) < 40%

          -  Prior history of treatment with blinatumomab

          -  Treatment with any investigational antileukemic agents or chemotherapy agents in the
             last two weeks, unless full recovery from side effects has occurred or patient has
             rapidly progressive disease judged to be life-threatening by the investigator

          -  Pregnant and lactating women will not be eligible; women of childbearing potential
             should have a negative pregnancy test prior to entering on the study and be willing to
             practice methods of contraception; women do not have childbearing potential if they
             have had a hysterectomy or are postmenopausal without menses for 12 months; in
             addition, men enrolled on this study should understand the risks to any sexual partner
             of childbearing potential and should practice an effective method of birth control