Phase I Study of B Cell Malignancies Using T Cells Expressing an Anti-CD19 Chimeric Receptor: Assessment of the Impact of Lymphocyte Depletion Prior to T Cell Transfer
This study is currently recruiting participants.
Verified October 2013 by National Institutes of Health Clinical Center (CC)
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
First received: June 17, 2009
Last updated: November 27, 2013
Last verified: October 2013
- CD19 is an antigen (protein) found on the surface of B cells, a type of white blood cell that helps the immune system by making antibodies. Cancerous B cells also express CD19.
- An experimental cancer treatment under development at the National Institutes of Health involves taking a sample of a patient s blood, using that sample to produce anti-CD19 cells, and then using the created cells to treat the cancer. This kind of treatment is known as gene therapy, and is very closely monitored by various government agencies.
- To determine the safety and usefulness of anti-CD19 cells created through gene therapy, including the maximum tolerated dose (the highest dose that does not cause unacceptable side effects).
- To see if anti-CD19 cells given in conjunction with chemotherapy drugs, fludarabine, and cyclophosphamide has any effect on the treatment of the cancer.
- Patients greater than or equal to 18 and less than or equal to 68 years of age who have been diagnosed with cancer that involves B cells, in which more than 50 percent of the cancerous cells are CD19-expressing B cells.
- Women who are pregnant or breastfeeding are not eligible.
- Pretreatment period (3 weeks before the start of the treatment):
- Physical examination and full medical history to determine eligibility.
- Heart and lung function tests and blood and bone marrow samples, including leukapheresis (blood sampling procedure that removes white blood cells for use in the lab).
- Insertion of an IV catheter for the treatment.
- For patients in the chemotherapy group, treatment with fludarabine and cyclophosphamide for 1 week before start of anti-CD19 study.
- Days 0 4: Infusion with anti-CD19 cells, followed by treatment with chemotherapy (15-minute infusion every 8 hours over 5 days) on an inpatient basis.
- Evaluations during the treatment and inpatient recovery period:
- Physical examination, including vital signs and body weight checks.
- Blood and urine tests.
- Possibly biopsy sample of lymph node to evaluate the effects of the treatment on the immune system.
- Blood and biopsy samples may be kept for further research with patient s consent.
Chronic Lymphocytic Leukemia
Small Lymphocytic Lymphoma
Mantle Cell Lymphoma
Large Cell Lymphoma
Genetic: Anti-CD19-CAR Transduced PBL
Drug: PG13-CD19-H3 (anti-CD19-CAR) transduced PBL)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Assessment of the Safety and Feasibility of Administering T Cells Expressing an Anti-CD19 Chimeric Antigen Receptor to Patients With B-cell Lymphoma or Leukemia|
Resource links provided by NLM:
U.S. FDA Resources
Further study details as provided by National Institutes of Health Clinical Center (CC):
Primary Outcome Measures:
- Determine the safety and feasibility of the administration of anti-CD19-CAR engineered peripheral blood lymphocytes and aldesleukin with a nonmyeloablative conditioning regimen in patients with B-cell malignancies.
Secondary Outcome Measures:
- Determine the in vivo survival of the anti-CD19-CAR-transduced T cells. Determine if the treatment regimen cause regression of B-cell malignancies.
|Study Start Date:||February 2009|
|Estimated Study Completion Date:||April 2014|
|Estimated Primary Completion Date:||April 2014 (Final data collection date for primary outcome measure)|
Intervention Details:Detailed Description:
Genetic: Anti-CD19-CAR Transduced PBL
N/ADrug: PG13-CD19-H3 (anti-CD19-CAR) transduced PBL)
- We have constructed a retroviral vector that encodes an anti-CD19 chimeric antigen receptor (CAR) that recognizes the CD19 antigen. This chimeric receptor also contains the signaling domains of CD28 and CD3-zeta. The retroviral vector can be used to mediate genetic transfer of this CAR to T cells with high efficiency (> 50%) without the need to perform any selection.
- In co-cultures with CD19-expressing target cells, anti-CD19-CAR-transduced T cells secreted significant amounts of IFN- >=( and IL-2. Anti-CD19-CAR-transduced T cells could specifically recognize and kill primary chronic lymphocytic leukemia cells.
- Primary objectives
- Determine the safety and feasibility of the administration of anti-CD19-CAR engineered peripheral blood lymphocytes with a nonmyeloablative conditioning regimen in patients with B-cell malignancies.
- Secondary objectives:
- Determine the in vivo survival of the anti-CD19-CAR-transduced T cells.
- Determine if the treatment regimen cause regression of B-cell malignancies.
Patients of 18 years of age or older must:
- have a CD19-expressing B-cell malignancy of any type
- be a non-responder to, or recurred after one or more standard chemotherapy-containing regimens for their malignancy
- currently require treatment due to progressive malignancy
- deemed to be incurable by standard therapy
Patients may not have:
- a history of allogeneic stem cell transplantation
- CNS disease
- PBMC obtained by leukapheresis (approximately 5 X 109 cells) will be cultured in the presence of anti-CD3 (OKT3) and aldesleukin in order to stimulate T-cell proliferation.
- Transduction is initiated by exposure of approximately 108 to 5 X 108 cells to retroviral vector supernatant containing the anti-CD19 CAR.
- Patients will receive fludarabine and cyclophosphamide chemotherapy (NMA) for lymphocyte-depletion, and anti-CD19-CAR-transduced T cells.
- Patients will be followed until disease progression
- Patients who have responded to treatment and then progress may receive one retreatment
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00924326
|Contact: June Kryk, R.N.||(301) firstname.lastname@example.org|
|Contact: Steven A Rosenberg, M.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact NCI/Surgery Branch Recruitment Center 866-820-4505 firstname.lastname@example.org|
Sponsors and Collaborators
|Principal Investigator:||Steven A Rosenberg, M.D.||National Cancer Institute (NCI)|