Single center Phase 1 dose escalation trial of the combination of standard-of-care blinatumomab plus Haplo-Mismatched Cellular Therapy (HMCT). HMCT refers to the infusion of donor peripheral blood mononuclear cells collected via pheresis from a haploidentical family member - the procedure is analogous to giving a donor lymphocyte infusion outside of the setting of an allogeneic stem cell transplant; also known as 'microtransplantation'. The HMCT is an unselected mix of lymphocytes and leukocytes, but the product dose escalation will be done based on the T cell content. Ten recipients are planned. Each subject will be administered one infusion of HMCT during the first cycle of blinatumomab and two infusions during cycle two of blinatumomab; the CD3+ cell dose of the HMCT infusion is governed by dose escalation / de-escalation following a Bayesian method.
This single center, phase 1 study will examine the safety, side effects, and effectiveness of combining the investigational use of Haplo-Mismatched Cellular Therapy (HMCT) in combination with blinatumomab. Investigators plan to give HMCT starting on day 15, after the initial CRS caused by blinatumomab has resolved. The investigational treatment will start with 1% of the typical HMCT dose (10e6 CD3+ cells/kg) and will employ a modified dose escalation design as an additional safety measure. The primary end points will be DLT of the combination of blinatumomab and HMCT.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
22
Blinatumomab per package insert - via continuous infusion days 1-28 of Cycle 1 and Cycle 2, every 42 days.
HMCT infusion Cycle 1, Day 15 and Cycle 2, Day 8 \& Day 15
Cedars-Sinai Medical Center
Los Angeles, California, United States
Incidence of DLTs
Number of Dose Limiting Toxicities experienced by patients undergoing HLA mismatched cellular therapy (HMCT) of allogenic CD3+ cells in combination with blinatumomab.
Time frame: up to 6 months
Number of participants experiencing complete response (CR) from time of transplant to one day following the second treatment
Bone marrow aspiration and local peripheral blood counts will be used to measure response. CR is defined as the following: * Less than or equal to 5% blasts in the bone marrow * No evidence of disease, AND * Full recovery of peripheral blood counts: platelets \> 100,000/ul, and ANC \> 1000/ul
Time frame: up to 3 months
Number of participants experiencing complete response with partial recovery of peripheral blood counts (CRh) from time of transplant to one day following the second treatment
Bone marrow aspiration and local peripheral blood counts will be used to measure response. CRh is defined as the following: * Less than or equal to 5% blasts in the bone marrow * No evidence of disease, AND * Full recovery of peripheral blood counts: platelets \> 50,000/ul, and ANC \> 500/ul
Time frame: up to 3 months
Number of participants experiencing complete response with incomplete count recovery (CRi) from time of transplant to one day following the second treatment
Bone marrow aspiration and local peripheral blood counts will be used to measure response. CRi is defined as the following: * Less than or equal to 5% blasts in the bone marrow * No evidence of disease, AND * Full recovery of peripheral blood counts: platelets \> 100,000/ul, and ANC \> 1000/ul
Time frame: up to 3 months
Response blast-free hypoplastic or aplastic bone marrow from time of transplant to one day following the second treatment
Bone marrow aspiration and local peripheral blood counts will be used to measure response. Blast-free hypoplastic or aplastic bone marrow response is defined as the following: * Less than or equal to 5% blasts in the bone marrow * No evidence of disease, AND * Full recovery of peripheral blood counts: platelets \> 50,000/ul, and ANC \> 500/ul
Time frame: up to 3 months
Disease burden measured as the minimal residual disease (MRD) response from time of transplant to one day following the second treatment
MRD remission is defined as the occurrence of an MRD level below 10\^-4 measured by quantitative reverse transcription polymerase chain reaction (PCR) or flow cytometry. Complete response defined as: no detectable leukemic cells by PCR or flow cytometry.
Time frame: up to 3 months
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