Blinatumomab in Treating Younger Patients With Relapsed B-cell Acute Lymphoblastic Leukemia
Condition: Recurrent B Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Intervention: Allogeneic Hematopoietic Stem Cell Transplantation; Asparaginase; Blinatumomab; Cyclophosphamide; Cytarabine; Dexamethasone; Etoposide; Leucovorin Calcium; Mercaptopurine; Methotrexate; Mitoxantrone; Mitoxantrone Hydrochloride; Pegaspargase; Pharmacological Study; Radiation Therapy; Therapeutic Hydrocortisone; Thioguanine; Vincristine; Vincristine Sulfate
Intervention description: Undergo allogeneic HSCT; Given IM or IV; Given IV; Given IV; Given IT and IV or SC; Given PO or IV; Given IV; Given IV or PO; Given PO; Given IT, IV, and PO; Given IV; Given IV; Given IV; Correlative studies; Undergo cranial radiation therapy; Given IT; Given PO; Given IV; Given IV
Intervention MeSH terms: Calcium, Dietary; Leucovorin; Folic Acid; Cytarabine; Dexamethasone; Dexamethasone acetate; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Cyclophosphamide; Methotrexate; Etoposide; Vincristine; Etoposide phosphate; Asparaginase; Mitoxantrone; Mercaptopurine; Podophyllotoxin; Pegaspargase; Thioguanine; Blinatumomab; Antineoplastic Agents, Immunological; Muromonab-CD3; Antibodies; Immunoglobulins; Antibodies, Monoclonal; Antibodies, Bispecific; BB 1101; Calcium; 2-Aminopurine; Levoleucovorin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 669.0
Sex: All
Minimum age: 1 Year
Maximum age: 31 Years
Healthy volunteers: No

Summary:

      This randomized phase III trial studies how well blinatumomab works compared with standard
      combination chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that
      has returned after a period of improvement (relapsed). Immunotherapy with blinatumomab may
      allow the body's immune system to attack and destroy some types of leukemia cells. It is not
      yet known whether blinatumomab is more effective than standard combination chemotherapy in
      treating relapsed B-cell acute lymphoblastic leukemia.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patients >= 1 year and < 31 years of age at the time of relapse will be eligible

          -  First relapse of B-ALL, allowable sites of disease include isolated bone marrow,
             combined bone marrow and CNS and/or testicular, and isolated CNS and/or testicular;
             extramedullary sites are limited to the CNS and testicles

          -  No waiting period for patients who relapse while receiving standard maintenance
             therapy

          -  Patients who relapse on frontline therapy in phases other than maintenance must have
             fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy,
             or radiotherapy prior to entering this study

          -  Cytotoxic therapy: at least 14 days since the completion of cytotoxic therapy with the
             exception of hydroxyurea, which is permitted up to 24 hours prior to the start of
             protocol therapy, or maintenance chemotherapy, or intrathecal chemotherapy
             (methotrexate strongly preferred) administered at the time of the required diagnostic
             lumbar puncture to establish baseline CNS status

          -  Biologic (anti-neoplastic) agent: at least 7 days since the completion of therapy with
             a biologic agent; for agents that have known adverse events occurring beyond 7 days
             after administration, this period must be extended beyond the time during which
             adverse events are known to occur

          -  Stem cell transplant or rescue: patient has not had a prior stem cell transplant or
             rescue

          -  Patient has not had prior treatment with blinatumomab

          -  With the exception of intrathecal chemotherapy (methotrexate strongly preferred;
             cytarabine is permissible) administered at the time of the required diagnostic lumbar
             puncture to establish baseline CNS status, patient has not received prior
             relapse-directed therapy (i.e., this protocol is intended as the INITIAL treatment of
             first relapse)

          -  Patients must have a performance status corresponding to Eastern Cooperative Oncology
             Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and
             Lansky for patients =< 16 years of age

          -  Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70
             mL/min/1.73 m^2 or a serum creatinine based on age/gender as follows:

               -  1 to < 2 years: =< 0.6 mg/dL

               -  2 to < 6 years: =< 0.8 mg/dL

               -  6 to < 10 years: =< 1 mg/dL

               -  10 to < 13 years: =< 1.2 mg/dL

               -  13 to < 16 years: =< 1.5 mg/dL (males) and =< 1.4 mg/dL (females)

               -  >= 16 years: =< 1.7 mg/dL (males) and =< 1.4 mg/dL (females)

          -  Direct bilirubin < 3.0 mg/dL

          -  Shortening fraction of >= 27% by echocardiogram, or

          -  Ejection fraction of >= 50% by radionuclide angiogram

          -  All patients and/or their parent or legal guardian must sign a written informed
             consent

          -  All institutional, Food and Drug Administration (FDA), and National Cancer Institute
             (NCI) requirements for human studies must be met

        Exclusion Criteria:

          -  Patients with Philadelphia chromosome positive/breakpoint cluster region protein
             (BCR)-Abelson murine leukemia viral oncogene homolog 1 (ABL1)+ ALL are not eligible

          -  Patients with Burkitt leukemia/lymphoma or mature B-cell leukemia are not eligible

          -  Patients with T-lymphoblastic leukemia (T-ALL)/lymphoblastic lymphoma (T-LL) are not
             eligible

          -  Patients with B-lymphoblastic lymphoma (B-LL) are not eligible

          -  Patients with known optic nerve and/or retinal involvement are not eligible; patients
             who are presenting with visual disturbances should have an ophthalmologic exam and, if
             indicated, a magnetic resonance imaging (MRI) to determine optic nerve or retinal
             involvement

          -  Patients known to have one of the following concomitant genetic syndromes: Down
             syndrome, Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome,
             Shwachman syndrome or any other known bone marrow failure syndrome

          -  Patients with known human immunodeficiency virus (HIV) infection

          -  Patients with known allergy to mitoxantrone, cytarabine, or both etoposide and
             etoposide phosphate (Etopophos)

          -  Lactating females who plan to breastfeed

          -  Patients who are pregnant since fetal toxicities and teratogenic effects have been
             noted for several of the study drugs; a pregnancy test is required for female patients
             of childbearing potential

          -  Sexually active patients of reproductive potential who have not agreed to use an
             effective contraceptive method for the duration of their study participation

          -  Patients with pre-existing significant central nervous system pathology that would
             preclude treatment with blinatumomab, including: history of severe brain injury,
             dementia, cerebellar disease, organic brain syndrome, psychosis, coordination/movement
             disorder, or autoimmune disease with CNS involvement are not eligible; patients with a
             history of cerebrovascular ischemia/hemorrhage with residual deficits are not
             eligible; (patients with a history of cerebrovascular ischemia/hemorrhage remain
             eligible provided all neurologic deficits have resolved)

          -  Patients with uncontrolled seizure disorder are not eligible; (patients with seizure
             disorders that do not require antiepileptic drugs, or are well controlled with stable
             doses of antiepileptic drugs remain eligible)