This trial will assess the feasibility of alpha/beta T-cell and B-cell depleted allogeneic hematopoietic cell transplantation (HCT) followed by blinatumomab therapy for high-risk B cell acute lymphoblastic leukemia (ALL) as a means of reducing rates of subsequent relapse and improving survival, while also minimizing treatment-related morbidity/ mortality and late effects. The conditioning regimens will be dependent on the patient's minimal residual disease (MRD) status prior to HCT using high throughput sequencing.
This trial evaluates the ability of a biologically active therapy in blinatumomab, an anti-CD19/CD3 bispecific T-cell engager, to further reduce the risk of leukemia relapse following HCT to improve post-HCT outcomes. The investigators will also utilize an alpha-beta T-cell and B-cell depleted graft to reduce the risk of GVHD along with a reduced intensity conditioning regimen without the use of TBI in patients who are minimal residual disease (MRD) negative using high throughput sequencing (HTS) prior to HCT. For those patients who remain HTS-MRD positive, a myeloablative conditioning regimen will be utilized, also followed by blinatumomab. This multi-institutional pilot study will be limited to 25 (estimated 10-15 per stratum) evaluable children, adolescents and young adults with B-ALL, that have experienced a relapse or have high-risk disease.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
25
Device: Alpha/Beta T-cell and B-cell depletion
28 day continuous infusion given on Day 100 post-HCT if no significant ongoing GVHD
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
RECRUITINGPercentage of patients who are able to receive the blinatumomab infusion [Feasibility]
Percentage of patients who are able to receive the blinatumomab infusion at day +100 post-HCT and complete a minimum of 14/28 planned days
Time frame: Day +100 post-HCT
Cumulative incidence of treatment-related adverse events [Tolerability]
As defined by cumulative incidence of treatment-related adverse events of blinatumomab post-HCT
Time frame: Day of HCT to Day +180 post-HCT
Overall Survival
Defined as the time interval from the date of transplant to death or last follow up
Time frame: Day of HCT to 1 year post-HCT
Disease Free Survival
Defined as the time interval from the date of transplant to death or last follow up or disease relapse
Time frame: Day of HCT to 1 year post-HCT
Engraftment
Defined as the number of patients who achieve ANC \> 500/uL for 3 consecutive days
Time frame: Day +100 and +1 year post-HCT
Primary Graft Failure
is defined as failure to achieve ANC \> 500/uL by Day +28
Time frame: Day +28 and + 1 year post-HCT
Secondary Graft Failure
Patients who initially achieve neutrophil engraftment followed by a decline in ANC \< 500/uL that is unresponsive to growth factor therapy
Time frame: Day +28 and +1 year post-HCT
Treatment Related Mortality
Defined as death occurring in a patient from causes other than disease relapse or progression
Time frame: Day of HCT to Day +100 and 1 year post-HCT
Acute & Chronic GVHD
Incidences of Grades 2-4 and Grades 3-4 acute GVHD
Time frame: Day +100, +180 and 1 year post-HCT
Patient Reported Outcomes
PROMIS Pediatric/Parent Proxy Profile 25 (either pediatric self-report if age 8-17 or parent proxy if age 5-8, or both if feasible) or PROMIS-29 Profile if age 18 or older
Time frame: Baseline, Day +100, +180, +1 year post-HCT
Length of Stay
Define by the total number of days a patient spends in the hospital
Time frame: Number of days between the day of transplantation, Day 0, and Day +180 post-HCT
Persistence of Minimal Residual Disease (MRD) Negativity
Number of patients remaining MRD negative by flow cytometry and/or high throughput sequencing
Time frame: Days +28, +100, +180 and +1 year post-HCT
Relapse
Cumulative incidence of relapse in all patients
Time frame: Day of HCT to day +180 and 1 year post-HCT
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.