Safety Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands
|Acute Myeloid Leukemia Myelodysplastic Syndrome Multiple Myeloma||Biological: CM-CS1 T-cell infusion||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1 Study of Chimeric Antigen Receptor Modified T-cells Targeting NKG2D-Ligands in Patients With Acute Myeloid Leukemia (AML)/Advanced Myelodysplastic Syndrome (MDS-RAEB) and Multiple Myeloma.|
- Safety and feasibility of intravenous administration of CM-CS1 T-cells. [ Time Frame: 24 months ]
Safety will be defined by the occurence of study-related serious and non-serious adverse events.
Feasibility will be defined by the frequency of subjects enrolled who do not receive CM-CS1 T-cells.
- Clinical and biologic responses [ Time Frame: 24 months ]Clinical anti-tumor effect by standard criteria Progression-Free survival Persistence and function of CM-CS1 T-cells
|Study Start Date:||March 2015|
|Estimated Primary Completion Date:||March 2017 (Final data collection date for primary outcome measure)|
Experimental: CM-CS1 T-cell infusion
The treatment will consist of a single infusion of CM-CS1 cells.
The following dose levels will be evaluated:
Cohort 1: 1x 10^6 CM-CS1 T-cells Cohort 2: 3x 10^6 CM-CS1 T-cells Cohort 3: 1x 10^7 CM-CS1 T-cells Cohort 4: 3x 10^7 CM-CS1 T-cells
Biological: CM-CS1 T-cell infusion
Each patient will receive a single dose of CM-CS1 T-cells by intravenous infusion.
This is a study for patients with AML or MDS-RAEB that is not in remission and for which there are no reasonable standard treatment options and for patients with relapsed/refractory multiple myeloma with progressive disease.
In this study, the participant's white blood cells (T-cells) will be collected and modified such that the T-cells are able to recognize specific molecules (called NKG2D-ligands), that are expressed on the surface of cancer cells in these diseases. This modification is a genetic change to the T-cells. The modified T cells, called CM-CS1 T-cells, are then given back to the participant by a single intravenous infusion. In this study, participants will not receive any chemotherapy prior to infusion of the CM-CS1 T-cells.
The study will evaluate whether it is safe and feasible to administer CM-CS1 T-cells to participants with AML/MDS-RAEB and multiple myeloma. It will also evaluate whether the CM-CS1 T-cells have a beneficial effect against the cancer cells. Another goal of the study is to learn more about the persistence and function of the CM-CS1 T-cells in the body.
Participants will be followed very closely during the first month after infusion. They are required to remain within 50 miles of Brigham and Women's Hospital (Boston, MA) for 10 days after the infusion and will be followed three times per week for the first 21 days and at day 28. Subsequently, participants will be followed monthly until 6 months after infusion, every 3 months until 15 months after infusion and at 24 months after infusion. Because this study involves gene transfer, participants will be followed yearly for up to 15 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02203825
|United States, Massachusetts|
|Dana-Farber Cancer Institute|
|Boston, Massachusetts, United States, 02215|
|Principal Investigator:||Sarah Nikiforow, MD; PhD||Dana-Farber Cancer Institute|