Therapy for Pediatric Relapsed or Refractory Precursor B-Cell Acute Lymphoblastic Leukemia and Lymphoma
Recurrent B-Cell Childhood Acute Lymphoblastic Leukemia, Recurrent Childhood B-Lymphoblastic Lymphoma
About this trial
This is an interventional treatment trial for Recurrent B-Cell Childhood Acute Lymphoblastic Leukemia focused on measuring leukemia, lymphoma, Non-Hodgkins
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:
- 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
- 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:
- In first relapse, OR
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:
- There is no waiting period for participants who relapse while receiving frontline therapy and are free from side effects attributable to such therapy.
- 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.
- 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.
Sites / Locations
- Rady Children's Hospital and Health Center
- St. Jude Children's Research Hospital
- Cook Children's Medical Center
Arms of the Study
Arm 1
Arm 2
Active Comparator
Active Comparator
Standard Risk
High Risk
Interventions: dexamethasone, vincristine sulfate, rituximab, clofarabine, cyclophosphamide, etoposide, aldesleukin, pegaspargase, methotrexate, mercaptopurine, cytarabine, mitoxantrone, teniposide, vinblastine, natural killer cell infusion, laboratory biomarker analysis, therapeutic hydrocortisone Cells for infusion are prepared using the CliniMACS System.
Interventions: dexamethasone, vincristine, rituximab, clofarabine, cyclophosphamide, etoposide, aldesleukin, pegaspargase, methotrexate, mercaptopurine, cytarabine, mitoxantrone, natural killer cell infusion, allogeneic hematopoietic stem cell transplantation, laboratory biomarker analysis, therapeutic hydrocortisone Cells for infusion are prepared using the CliniMACS System.