Allogeneic CD30 Chimeric Antigen Receptor Epstein-Barr Virus-Specific T Lymphocytes in Patients With Relapsed or Refractory CD30-Positive Lymphomas
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|ClinicalTrials.gov Identifier: NCT04952584|
Recruitment Status : Not yet recruiting
First Posted : July 7, 2021
Last Update Posted : July 7, 2021
This study involved patients that have a cancer called diffuse large B cell lymphoma (DLBCL), NK and T cell lymphomas (NK/TL) or classical Hodgkin lymphoma (cHL) (hereafter these 3 diseases will be referred to as lymphoma). Patients lymphoma has come back or not gone away after treatment. Because there is no standard treatment for the patients cancer at this time or because the currently used treatments do not work fully in all cases, the patients are being asked to volunteer in this research study.
In this study the investigators want to test a type of T cell made from a normal donor. The T cells the investigators will use are called Epstein Barr virus (EBV) specific T cells (EBVSTs) and are cells that the investigators have trained in the laboratory to recognize a EBV which is the virus that causes mono or kissing disease. Some patients with lymphoma have EBV in their cancer cells. Researchers have given T cell lines from normal donor EBVSTs to lymphoma patients who have EBV in their lymphoma cells and have seen responses in about half the patients. The cells have have been generated and are frozen in a bank. The cells are called "allogeneic" (meaning the donor is not related to the patient). CD30.CAR in EBV-specific T cells (called allogeneic CD30.CAR-EBVST) from the blood of healthy donors. The investigators are giving the cells to patients with lymphoma cells that express CD30. If the lymphoma cells also express EBV there may be some benefit from targeting both proteins.
The purpose of this study is to find out the highest safe dose of allogeneic CD30.CAR-EBVST cells given following chemotherapy and used to treat lymphoma. The investigators will learn the side effects of CD30.CAR-EBVST cells in patients and see whether this therapy may help lymphoma patients.
|Condition or disease||Intervention/treatment||Phase|
|Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type Classical Hodgkin Lymphoma||Biological: CD30.CAR-EBVST cells||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study Evaluating the Safety and Activity of Allogeneic CD30 Chimeric Antigen Receptor Epstein-Barr Virus-Specific T Lymphocytes (CD30.CAR-EBVSTs) in Patients With Relapsed or Refractory CD30-Positive Lymphomas|
|Estimated Study Start Date :||September 2021|
|Estimated Primary Completion Date :||June 2023|
|Estimated Study Completion Date :||June 2038|
Experimental: Treatment Phase
Three dose levels will be evaluated based on safety data from our current study of CD30 CAR T cells. Cohorts of three to six patients will be enrolled at each dose level The dose is based on the number of CD.30 CAR-EBVT-expressing cells administered. The total number of dose levels evaluated will depend upon toxicities experienced. Dose level cohorts will be numbered sequentially.
Dose Level 1: 1 × 10^8 CD30.CAR-EBVST cells
Dose Level 2: 4 × 10^8 CD30.CAR-EBVST cells
Dose Level 3: 1 × 10^9 CD30.CAR-EBVST cells
Biological: CD30.CAR-EBVST cells
The dose is based on the number of CD30.CAR-expressing cells. In our previous study the highest dose was 2 × 10^8 cells/m2 and we did not reach a MTD.
There will be a gap of 4 weeks between the first and second patient on each dose level.
On Day 0 of study, patients will receive their planned single dose of investigational T cell product by IV infusion over approximately 1 to 10 minutes in an expected volume of 1 to 50 mL.
Other Name: Allogeneic CD30 Chimeric Antigen Receptor Epstein-Barr Virus-Specific T Lymphocytes
- Dose limiting toxicity rate (DLT) by CTCAE 5.0 [ Time Frame: 28 Days ]Any Grade 5 event, / Non-hematologic dose-limiting toxicity is any Grade 3 or Grade 4 non-hematologic toxicity that fails to return to Grade 2 within 72 hours, / Grade 2-4 allergic reaction to T-Cells, / Grade 3-4 GVHD, / Grade 3-4 CRS. Toxicity will be evaluated according to the CTCAE Version 5.0. GVHD will be graded by the method of Przepiorka et al.
- Rate of Anti-Tumor effect Objective Response (OR) [ Time Frame: 4 to 12 weeks post CTL infusion ]Objective response rate is defined as complete response and partial response
- Duration of Response [ Time Frame: Up to 5 years ]Response duration will be measured from the time of initial response until documented tumor progression.
- Stable disease (SD) rate [ Time Frame: 4 to 12 weeks post CTL infusion ]SD will be defined as the proportion of patients that have stable disease
- Duration of SD [ Time Frame: Up to 5 years ]Stable disease is measured from the start of the treatment until the criteria for progression are met.
- Progression free survival (PFS) [ Time Frame: Up to 5 years ]PFS is defined as the time from treatment until objective tumor progression or death, whichever occurs first.
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): NCT04952584
|Contact: Premal Lulla||(713) email@example.com|
|Contact: Anaid Reyes||(832) 824-3855||Anaid.Reyes@bcm.edu|
|Principal Investigator:||Premal Lulla, MD||Baylor College of Medicine|