Phase 2
N=42
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
Bottom Line
View on ClinicalTrials.gov: NCT01700946 ↗Enrolled (actual)
42
Serious AEs
2.4%
Results posted
Sep 2022
Primary outcome: Primary: 3-year Overall Survival Rate of Patients With Relapsed ALL — 94.4; 55.5; 72.63 percentage of participants — p=0.035
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- dexamethasone (Drug); vincristine sulfate (Drug); rituximab (Biological); clofarabine (Drug); cyclophosphamide (Drug); etoposide (Drug); aldesleukin (Biological); pegaspargase (Drug); methotrexate (Drug); mercaptopurine (Drug); cytarabine (Drug); mitoxantrone (Drug); teniposide (Drug); vinblastine (Drug); natural killer cell infusion (Biological); laboratory biomarker analysis (Other); therapeutic hydrocortisone (Drug); allogeneic hematopoietic stem cell transplantation (Procedure); CliniMACS (Device)
- Age
- Pediatric, Adult
- Sex
- All
- Sponsor
- St. Jude Children's Research Hospital
- Primary completion
- Jul 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY 3-year Overall Survival Rate of Patients With Relapsed ALL |
94.4; 55.5; 72.63 | 0.035 sig |
| PRIMARY 3-year Event-free Survival Rates in Patients With Relapsed ALL |
83.3; 55.7; 67.83 | 0.105 |
| SECONDARY Proportion of Participants With Positive Minimal Residual Disease |
14; 6; 20; 22; 0; 4 | 0.1181 |
| SECONDARY Mean of CD20 Expression Levels |
31.10; 39.82; 36.23; 18.54; 20.10; 19.43 | — |
| SECONDARY Median CD20 Expression Levels |
16.40; 23.13; 22.0; 11.83; 19.58; 15.58 | — |
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:
- 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 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 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.
Data sourced from ClinicalTrials.gov (NCT01700946). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.