Therapy for Pediatric Relapsed or Refractory Precursor B-Cell Acute Lymphoblastic Leukemia and Lymphoma
Condition: Recurrent B-Cell Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood B-Lymphoblastic Lymphoma
MeSH terms: Lymphoma; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Recurrence
Intervention: dexamethasone; vincristine sulfate; rituximab; clofarabine; cyclophosphamide; etoposide; aldesleukin; pegaspargase; methotrexate; mercaptopurine; cytarabine; mitoxantrone; teniposide; vinblastine; natural killer cell infusion; laboratory biomarker analysis; therapeutic hydrocortisone; allogeneic hematopoietic stem cell transplantation; CliniMACS
Intervention description: given intravenously or orally; given intravenously; given intravenously; given intravenously; given intravenously; given intravenously; given subcutaneously; given intravenously; given intrathecally or intravenously; given orally; given intrathecally or intravenously; given intravenously; given intravenously; given intravenously; undergo allogeneic natural killer cell infusion; correlative studies; given intrathecally; undergo allogeneic HSCT; The mechanism of action of the CliniMACS Cell Selection System is based on magnetic-activated cell sorting (MACS). The CliniMACS device is a powerful tool for the isolation of many cell types from heterogeneous cell mixtures, (e.g. apheresis products). These can then be separated in a magnetic field using an immunomagnetic label specific for the cell type of interest, such as CD3+ human T cells.
Intervention MeSH terms: Cytarabine; Aldesleukin; Dexamethasone; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Cyclophosphamide; Rituximab; Methotrexate; Etoposide; Vincristine; Asparaginase; Interleukin-2; Mitoxantrone; Mercaptopurine; Clofarabine; Vinblastine; Pegaspargase; Teniposide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 80.0
Sex: All
Maximum age: 21 Years
Healthy volunteers: No
Keywords: leukemia; lymphoma; Non-Hodgkins

Summary:

      The overall objective of this protocol is to improve the cure rate of relapsed precursor
      B-cell acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma.

      This phase II trial is studying risk-directed therapy for B-lymphoblastic leukemia or
      lymphoma in first relapse. Standard risk (SR) and high risk (HR) participants will receive
      different therapy. Treatment will consist of chemotherapy for SR participants, and
      chemotherapy followed by hematopoietic stem cell transplant (HSCT) for HR in first relapse.
      Induction therapy consists of three blocks of chemotherapy. The first block is a novel
      immunotherapy regimen that includes chemotherapy, rituximab and infusion of haploidentical
      natural killer (NK) cells. SR participants will continue to receive chemotherapy for a total
      duration of approximately 2 years. HR participants will be candidates for HSCT and will
      proceed to transplant once a suitable donor is found and their minimal residual disease (MRD)
      is negative.
    

Eligibility criteria:

        INCLUSION CRITERIA:

          -  Must have relapsed or refractory precursor B-cell acute lymphoblastic leukemia or
             acute lymphoblastic lymphoma.

          -  Participants with leukemia must meet one of the following:

               1. In first hematologic relapse, defined as the reappearance (in a patient who has
                  previously achieved remission) of leukemia blasts in the bone marrow or
                  peripheral blood, OR

               2. Refractory to one or two courses of frontline induction therapy (≥ 5% blasts in
                  the bone marrow or peripheral blood confirmed by flow cytometric analysis).

          -  Participant with lymphoma must meet one of the following:

               1. In first relapse, OR

               2. Refractory to one or two courses of frontline induction therapy with measurable
                  disease

                    -  Should flow cytometric analyses suggest relapse (by the reappearance of a
                       similar immunophenotype to the original leukemia) in the presence of <5%
                       blasts morphologically, a repeat bone marrow test is recommended to confirm
                       relapse.

                    -  Molecular or genetic relapse is characterized by the reappearance of a
                       cytogenetic or molecular abnormality.

                    -  Early relapse is defined as relapse on therapy or < 6 months after
                       completion of frontline therapy. Late relapse is defined as relapse
                       occurring ≥ 6 months after completion of frontline therapy.

          -  Participant's age is < 22 years at time of enrollment (e.g. participant is eligible
             until 22nd birthday).

          -  Prior therapy:

               1. There is no waiting period for participants who relapse while receiving frontline
                  therapy and are free from side effects attributable to such therapy.

               2. Emergent radiation therapy, one dose of intrathecal chemotherapy, and up to 7
                  days of steroids for treatment of relapse are permitted before start of treatment
                  in participants who relapse after completion of frontline therapy.

               3. At least 90 days have elapsed since bone marrow transplant and participant is off
                  immune suppression for a minimum of 2 weeks, if applicable. Participants with ALL
                  or NHL who were transplanted in first remission are eligible for this study.

        Organ function requirements

          -  Hepatic: Total bilirubin ≤ upper limit of normal (ULN) for age, or if total bilirubin
             is > ULN, direct bilirubin ≤ 1.4 mg/dl

          -  Cardiac: Shortening fraction ≥ 28%

          -  Renal: Glomerular filtration rate >50cc/min/1.73 m^2, OR maximum serum creatinine (SC)
             based on age as follows:

               -  If age is 1 to 2 years, then maximum SC is 0.6 mg/dL

               -  If age is 2 to 6 years, then maximum SC is 0.8 mg/dL

               -  If age is 6 to 10 years, then maximum SC is 1 mg/dL

               -  If age is 10 to <13 years, then maximum SC is 1.2 mg/dL

               -  If age is 13 to 16 years, then maximum SC is 1.5 mg/dL for males and 1.4 mg/dL
                  for females

               -  If age is >16 years, then maximum SC is 1.7 mg/dL for males and 1.4 mg/dL for
                  females

        EXCLUSION CRITERIA:

          -  Leukemia participants ages 1 to 5 years with induction failure AND favorable
             cytogenetics (i.e., hyperdiploidy defined as DNA index ≥1.16 or modal chromosome
             number ≥51, or ETV6-RUNXI).

          -  Hepatitis B or HIV infection.

          -  Pregnant or breast-feeding

          -  Inability or unwillingness or research participant or legal guardian/representative to
             give written informed consent.

        INCLUSION CRITERIA FOR NK CELL DONORS:

          -  Donor is at least 18 years of age.

          -  Donor is a family member.