Therapy for Pediatric Relapsed or Refractory Precursor B-Cell Acute Lymphoblastic Leukemia and Lymphoma

• Status: Completed
• Trial end date: 2021-07-24
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: St. Jude Children's Research Hospital
• Collaborators: Assisi Foundation; Cookies for Kids' Cancer
• Treatments: 6-Mercaptopurine; Aldesleukin; Asparaginase; BB 1101; Clofarabine; Cortisol succinate; Cyclophosphamide; Cytarabine; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Etoposide; Etoposide phosphate; Hydrocortisone; Hydrocortisone 17-butyrate 21-propionate; Hydrocortisone acetate; Hydrocortisone hemisuccinate; Interleukin-2; Mercaptopurine; Methotrexate; Mitoxantrone; Pegaspargase; Rituximab; Teniposide; Vinblastine; Vincristine

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.