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. (see Contacts and Locations)
Verified June 2014 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: July 22, 2014
Last verified: June 2014
- 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
Biological: Anti-CD19-CAR PBL
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy 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:
Genetic and Rare Diseases Information Center resources: B-cell Lymphomas Chronic Lymphocytic Leukemia Follicular Lymphoma Leukemia, B-cell, Chronic Lymphoma, Large-cell Lymphosarcoma Mantle Cell LymphomaU.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 with a nonmyeloablative conditioning regimen in patients with B-cell malignancies. [ Time Frame: approximately 4 years ] [ Designated as safety issue: Yes ]
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:||January 2017|
|Estimated Primary Completion Date:||January 2017 (Final data collection date for primary outcome measure)|
Experimental: Single Arm
Patients will receive fludarabine and cyclophosphamide chemotherapy (NMA) for lymphocyte-depletion followed by anti-CD19- CAR-transduced T cells
On days -5 through -3, Fludarabine 30mg/m2 IV will be infused over 30 minutes.Drug: Cyclophosphamide
On days -5 through -3, Cyclophosphamide 300mg/m2 IV will be infused over 60 minutes followed by fludarabine.Biological: Anti-CD19-CAR PBL
On day 0, cells will infused intravenously (IV) on the patient care unit over 20 - 30 minutes (2-4 days after the last dose of fludarabine).
- 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.
- We have developed a process for cryopreserving the cell product which may lead to the ability for this product to be manufactured at a central location and shipped to other institutions for treatment of a broader patient population
- Primary objectives
- With the approval of amendment S, determine the safety and feasibility of the administration of cryopreserved anti-CD19-CAR engineered peripheral blood lymphocytes with a nonmyeloablative conditioning regimen in patients with B-cell malignancies.
- Secondary objectives:
- With the approval of amendment S, determine the in vivo survival of the cryopreserved anti-CD19-CAR-transduced T cells.
- Determine if the treatment regimen can 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.
- With the approval of amendment S, patients will receive fludarabine and cyclophosphamide chemotherapy (NMA) for lymphocyte-depletion, followed by cryopreserved 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00924326
Please refer to this study by its ClinicalTrials.gov identifier: NCT00924326
|Contact: Linda Williams, R.N.||(866) email@example.com|
|Contact: Steven A Rosenberg, M.D.||(301) firstname.lastname@example.org|
|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 email@example.com|
Sponsors and Collaborators
|Principal Investigator:||Steven A Rosenberg, M.D.||National Cancer Institute (NCI)|