This phase I trial studies the side effects and best dose of blinatumomab when given with
nivolumab alone or nivolumab and ipilimumab in treating patients with poor-risk CD19+
precursor B-lymphoblastic leukemia that has come back after a period of improvement
(relapsed) or has not responded to treatment (refractory). Immunotherapy with monoclonal
antibodies, such as blinatumomab, nivolumab, and ipilimumab, may help the body's immune
system attack the cancer, and may interfere with the ability of tumor cells to grow and
I. To evaluate the safety and tolerability of the blinatumomab given in combination with
nivolumab alone, or in combination with both nivolumab and ipilimumab in subjects with
poor-risk, relapsed or refractory CD19+ pre-B cell acute lymphoblastic leukemia (ALL) or
CD19+ mixed phenotype acute leukemia (MPAL).
II. To determine the maximum tolerated dose (MTD) of the combination of blinatumomab plus
nivolumab, and blinatumomab plus both nivolumab and ipilimumab and to further confirm the
safety of the combination therapy in subjects with poor-risk, relapsed or refractory CD19+
pre-B cell ALL or CD19+ mixed phenotype acute leukemia (MPAL).
I. To observe and record anti-leukemia activity of blinatumomab and nivolumab, and
blinatumomab plus both nivolumab and ipilimumab, including the effects on minimal residual
II. To assess preliminary anti-leukemia activity in expansion cohorts of patients with
poor-risk, relapsed or refractory CD19+ precursor B-lymphoblastic leukemia, or CD19+ mixed
phenotype acute leukemia (MPAL).
I. To examine changes in absolute lymphocyte count and distribution of T cell subsets (CD4+,
CD8+, regulatory T cells [Tregs], effector T cells [Teffs]) and their differentiation status,
natural killer (NK) cells, and B cells before and post-blinatumomab, and immune checkpoint
inhibitor(s) therapy in both peripheral blood and the bone marrow microenvironment.
II. To explore changes in T cell co-signaling receptors expression in defined T cell
subpopulations and their canonic transcription factor expression in both peripheral blood and
bone marrow before and post-blinatumomab, and immune checkpoint inhibitor(s) therapy.
III. To examine changes in expression of co-signaling molecules on leukemia blasts
(CD10+/CD19+/CD34+) before and after treatment with blinatumomab and checkpoint inhibitors.
IV. To examine the serum levels of cytokines before and after treatment with blinatumomab and
checkpoint inhibitors, including the levels of sCTLA-4.
V. To perform immune profiling of T cell repertoire and characterize T cell transcriptional
signature before and after treatment.
OUTLINE: This is a dose-escalation study of blinatumomab.
Patients receive blinatumomab intravenously (IV) continuously on days 1-28. Treatment repeats
every 42 days for up to 5 cycles in the absence of disease progression or unacceptable
toxicity. Patients also receive nivolumab IV over 30 minutes on day 11 and then every 2 weeks
for up to year. Some patients also receive ipilimumab IV over 90 minutes on day 11 and then
every 6 weeks for up to 1 year.
After completion of study treatment, patients are followed up every 3 months for up to 2
Mixed Phenotype Acute Leukemia, Refractory Mixed Phenotype Acute Leukemia, Mixed Phenotype Acute Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, Refractory B Acute Lymphoblastic Leukemia, Recurrent Mixed Phenotype Acute Leukemia, B Acute Lymphoblastic Leukemia, Recurrent B Acute Lymphoblastic Leukemia, B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1, Allogeneic Hematopoietic Stem Cell Transplant Recipient, CD19-Positive Neoplastic Cells Present, Allogeneic Hematopoietic Stem Cell Transplantation Recipient
If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.
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