BATs Treatment for Pancreatic Cancer, Phase Ib/II
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|ClinicalTrials.gov Identifier: NCT03269526|
Recruitment Status : Recruiting
First Posted : August 31, 2017
Last Update Posted : July 23, 2019
|Condition or disease||Intervention/treatment||Phase|
|Locally Advanced Pancreatic Adenocarcinoma Metastatic Pancreatic Adenocarcinoma||Drug: EGFR BATs after standard of care chemo||Phase 1 Phase 2|
Once subjects are determined eligible, white blood cells (lymphocytes) are collected via leukapheresis procedure at approximately 3 to 4 weeks prior to first EGFR-BATs infusion. The white blood cells, specifically T cells, are then mixed with two proteins - OKT3 and IL-2 which activates the cells to multiply. After approximately 14 days in culture, the activated T cells are coated with the OKT3 and cetuximab to produce bispecific antibody armed T cells (BATs). Cells are then frozen and stored until scheduled to be infused.
Within one to two weeks prior to infusion of the study treatment, subjects will receive one dose of chemotherapy. The choice of chemotherapy agent(s) is at the discretion of the treating physician.
At approximately 4 weeks following leukapheresis procedure, twice weekly or weekly infusions of the BATs cells will take place (twice weekly for participants enrolled before DATE and weekly for participants enrolled after DATE). A total of eight twice weekly infusions or four weekly infusions will be given over a four week period. Please note that the weekly dose for both groups of participants is the same; participants that received twice weekly dosing received half of the weekly dose at each infusion.
Follow-up appointment schedule will include clinic visits at 1 to 2 weeks, 4 to 5 weeks, 2 months, 4 months and 6 months following the last infusion of BATs cells.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||22 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Standard of care chemotherapy followed by Anti-CD3 x anti-EGFR-Bispecific Antibody Armed Activated T-cells|
|Masking:||None (Open Label)|
|Official Title:||Phase Ib/II Treatment of Advanced Pancreatic Cancer With Anti-CD3 x Anti-EGFR-Bispecific Antibody Armed Activated T-Cells (BATs)|
|Actual Study Start Date :||July 28, 2017|
|Estimated Primary Completion Date :||June 1, 2020|
|Estimated Study Completion Date :||June 1, 2022|
Experimental: EGFR BATs after standard of care chemo
Subjects will undergo apheresis to collect peripheral blood mononuclear cells. Cells will be cultured for up to 2 weeks before activated T-cells will be harvested, armed with EGFR Biarmed activated T-cells, washed to remove unbound EGFRBi, and cryopreserved. Subjects will then receive one dose of standard of care chemotherapy prior to receiving EGFR BATs.
Drug: EGFR BATs after standard of care chemo
Subjects will receive one dose of standard of care chemotherapy prior to twice weekly or weekly infusions of EGFR BATs for 4 weeks.
- Incidence of adverse events [ Time Frame: From the beginning of treatment (bridging chemotherapy) until no sooner than 30 days following the last study treatment ]Safety will be assessed by incidence and severity of adverse events, changes in laboratory findings, physical examinations, vital signs, and the number of dose limiting toxicities and other discontinuations due to adverse events.
- Overall survival [ Time Frame: Until subject's death or study closure (whichever occurs first) for an average of 36 months from study treatment completion ]An improvement in median overall survival (OS), defined as an increase from historical data of 8.7 months to 18.0 months.
- Cellular or humoral anti-pancreatic cancer responses [ Time Frame: Every 2-6 months after the last EGFR BATs infusion for as long as the response lasts -- an average of 4 months ]These will be measured in peripheral blood mononuclear cells
- Clinical Efficacy [ Time Frame: Imaging will be performed prior to treatment, 2 months after the last BATs infusion, then according to standard of care for an average of 12 months ]Progression-free survival, measured by immune-related response criteria (irRC)
- Examine tumor tissue for immune system cells, cytokines and proteins to estimate whether the type and number of immune cells correlates with clinical responses [ Time Frame: Tumor paraffin blocks from tissue collected prior to treatment will be batched and analyzed within 1 year of completion of study accrual ]These immune system cells, cytokines and proteins include CD3, CD4, CD8, PD1/PDL1, monocytes subpopulations, MDSCs, and cytoplasmic IFN-y, tumor infiltrating lymphocytes, and IL-10. This will be measured using immunohistochemical staining to quantitate type and number of immune system cells, cytokines, and proteins to estimate whether the type and number correlate with clinical responses.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03269526
|Contact: Ioannis Vassalos, MDfirstname.lastname@example.org|
|Contact: Lawrence Lum, MD, DScemail@example.com|
|United States, Virginia|
|University of Virginia||Recruiting|
|Charlottesville, Virginia, United States, 22908|
|Contact: Melissa Otoya, RN, MSN-CNL 434-982-3365 firstname.lastname@example.org|
|Principal Investigator: Tri Le, MD|
|Principal Investigator:||Tri Le, MD||University of Virginia|