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.
In remission after first relapse or greater (≥ CR2)
Very-high risk biology ALL that is proceeding to HCT in first remission (e.g. Induction failure, Severe-hypodiploidy, Ph-like ALL)
First remission with persistent disease identified as end of consolidation (EOC) MRD > 0.01%.
Patients must have an available unrelated or haploidentical donor
Active extramedullary disease or presence of chloromatous disease.
Receiving concomitant chemotherapy, radiation therapy; immunotherapy or other anti-cancer therapy for treatment of disease other than is specified in the protocol.
Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment). Patients with possible fungal infections must have had at least 2 weeks of appropriate anti-fungal antibiotics and be asymptomatic.
Pregnant or lactating. The agents used in this study are known to be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 7 days prior to registration to rule out pregnancy.
Parallel
Alpha/Beta T-cell and B-cell depleted HCT
DeviceDevice: Alpha/Beta T-cell and B-cell depletion
Blinatumomab
Drug28 day continuous infusion given on Day 100 post-HCT if no significant ongoing GVHD
Percentage 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
Cumulative incidence of treatment-related adverse events [Tolerability]
As defined by cumulative incidence of treatment-related adverse events of blinatumomab post-HCT
Overall Survival
Defined as the time interval from the date of transplant to death or last follow up
Disease Free Survival
Defined as the time interval from the date of transplant to death or last follow up or disease relapse
Engraftment
Defined as the number of patients who achieve ANC \> 500/uL for 3 consecutive days
Analysis of immune cell phenotyping
Reconstitution of T, B, and NK cell subsets in the peripheral blood will be analyzed by immune cell phenotyping using flow cytometry.
Functional assessment of lymphocyte subsets
To assess lymphocyte function, peripheral blood mononuclear cells will be co-cultured with stimulator cells in the presence or absence of blinatumomab.
Serum cytokine analysis
Plasma cytokines will be measured to examine pro and anti-inflammatory cytokines, chemokines and growth factors produced by donor cells during immune reconstitution and GVHD. The plasma cytokines Eotaxin, Eotaxin-3, GM-CSF, IFN-γ, IL-10, IL-12p70, IL-12/IL-23p40, IL-13, IL-15, IL-16, IL-17A, IL-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IP-10, MCP-1, MCP-4, MDC, MIP-1α, MIP-1β, TARC, TNF-α, TNF-β, VEGF-A, and IL-8 will be measured using a multiplex cytokine analyzer where 10 antibodies specific for the above cytokines are attached to a single well providing cytokine capture and immune specificity.
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Medical College of Wisconsin
Lead sponsor
Amgen
Collaborator
University of Wisconsin, Madison
Collaborator
