Safety Study of Anti LewisY Chimeric Antigen Receptor in Myeloma, Acute Myeloid Leukemia or Myelodysplastic Syndrome
Recruitment status was: Active, not recruiting
Patients with some forms of acute myeloid leukemia (AML) and multiple myeloma (MM) are not cured with conventional therapy and new approaches are needed. For the last 15 years we have investigated the potential of using a patient's own T cells (a type of white blood cell [WBC]) to eradicate the tumor. We have demonstrated the feasibility of this approach in cell culture and animal models of AML and MM. Over the last 5 years we have been preparing to treat patients as part of a Phase I (first in human) clinical trial.
The trial treatment involves collecting the patient's own WBCs from the blood by a standard well established and safe process called apheresis. The cells are then cultured in a specialized laboratory (under Good Manufacturing Practice conditions, similar to standards under which pharmaceuticals are produced) over 12 days to convert the cells to specialized tumor-attacking T cells. Early in that culture process the cells are exposed to a virus (that is modified so that it cannot infect or replicate outside the special culture conditions) that contains a special gene. Via the virus, this gene inserts into the patient's T cells in culture and gets incorporated into the T cell's genetic machinery. As the T cells replicate, the new gene produces a protein receptor that becomes part of the patient's T cells. This protein receptor on the T cells has the capacity to specifically recognize and bind to a protein on the leukemia or myeloma cells called the "Lewis Y" antigen.
After the modified T cells are infused into the patient, they home into the bone marrow (this tracking is monitored by special radiological techniques) where the new protein receptor on the T cell surface can recognize and bind to the cancer cells (which express Lewis Y). Once bound onto the cancer cells, the T cells get activated and subsequently replicate and kill the cancer cells. The novelty of this approach is that the T-cells will only kill cells that have the Lewis Y on their surface - the cancer cells. Moreover, because there are few normal cells in a person's body that carry Lewis Y, this treatment is likely to only have minor side effects.
This gene therapy trial is unique and although the primary purpose is to test the safety of this approach, patients will be monitored closely for anti-tumor responses. As the trial progresses, the dose of T cells infused will increase, in the hope that this will result in a better and stronger immune response to the leukemia or myeloma.
|Multiple Myeloma Acute Myeloid Leukaemia Myelodysplastic Syndrome||Biological: Anti-LeY- scFv-CD28-ζ vector,.||Phase 1|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase I Study Investigating Safety Immunological Effects of Peripheral Blood T Lymphocytes Transduced With Anti LewisY Chimeric Receptor Gene in LewisY Positive Myeloma, Acute Myeloid Leukemia or High Risk Myelodysplastic Syndrome|
- Number of participants with adverse events. [ Time Frame: Up to 3 years ]
- Percentage of infused labelled cells localizing in bone marrow [ Time Frame: Up to 3 years ]
- Percentage of infused labelled cells localizing in soft tissue or plasmacytoma. [ Time Frame: Up to 3 years ]
- Presence or absence of anti-LeY positive T-cells in peripheral blood and bone marrow. [ Time Frame: Up to 3 years ]
- Percentage of anti LeY positive T-cells in peripheral blood and bone marrow. [ Time Frame: Up to 3 years ]
- Serum IFN-γ and IL-2 levels. [ Time Frame: Up to 3 years ]
- Presence or absence of autoimmune disease. [ Time Frame: Up to 3 years ]
- Overall response. [ Time Frame: Up to 3 years ]
- Time to progression [ Time Frame: Up to 3 years ]
- Time to treatment failure [ Time Frame: Up to 3 years ]
- Duration of response [ Time Frame: Up to 3 years ]
- Overall survival [ Time Frame: Up to 3 years ]
- Location of labelled re-infused T-cells [ Time Frame: Up to 1 month ]
- LewisY expression assessed with Flow Cytometry in Peripheral Blood and Bone Marrow. [ Time Frame: Up to 3 years ]
- LewisY expression assessed with Flow Cytometry in Peripheral Blood and Bone [ Time Frame: Up to 3 years ]
|Study Start Date:||January 2010|
|Estimated Study Completion Date:||December 2013|
|Estimated Primary Completion Date:||December 2013 (Final data collection date for primary outcome measure)|
Experimental: Anti-LeY- scFv-CD28-ζ vector.
Anti-LeY- scFv-CD28-ζ vector, a non-pathogenic, replication-incompetent retroviral vector specifically designed for this study and produced by EUFETS under GMP-conditions.
|Biological: Anti-LeY- scFv-CD28-ζ vector,.|
Please refer to this study by its ClinicalTrials.gov identifier: NCT01716364
|Peter MacCallum Cancer Centre|
|Melbourne, Victoria, Australia, 3002|
|Principal Investigator:||Miles Prince, MD||Peter MacCallum Cancer Centre, Australia|