CD19 Chimeric Receptor Expressing T Lymphocytes In B-Cell Non Hodgkin's Lymphoma, ALL & CLL
CRETI-NH
Phase I Study Of CD19 Chimeric Receptor Expressing T Lymphocytes In B-Cell Non Hodgkin's Lymphoma, Acute Lymphocytic Leukemia, and Chronic Lymphocytic Leukemia
1 other identifier
interventional
14
1 country
2
Brief Summary
Patients on this study have a type of lymph gland cancer called non-Hodgkin Lymphoma, Acute Lymphocytic Leukemia, or chronic Lymphocytic Leukemia (these diseases will be referred to as "Lymphoma" or "Leukemia"). Their Lymphoma or Leukemia has come back or has not gone away after treatment (including the best treatment known for these cancers). This research study is a gene transfer study using special immune cells. The body has different ways of fighting infection and disease. No one way seems perfect for fighting cancers. This research study combines two different ways of fighting disease, antibodies and T cells, hoping that they will work together. Antibodies are types of proteins that protect the body from bacterial and other diseases. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells including tumor cells. Both antibodies and T cells have been used to treat patients with cancers; they have shown promise, but have not been strong enough to cure most patients. T lymphocytes can kill tumor cells but there normally are not enough of them to kill all the tumor cells. Some researchers have taken T cells from a person's blood, grown more of them in the laboratory and then given them back to the person. The antibody used in this study is called anti-CD19. It first came from mice that have developed immunity to human lymphoma. This antibody sticks to cancer cells because of a substance on the outside of these cells called CD19. CD19 antibodies have been used to treat people with lymphoma and Leukemia. For this study anti-CD19 has been changed so that instead of floating free in the blood it is now joined to the T cells. When an antibody is joined to a T cell in this way it is called a chimeric receptor. In the laboratory, investigators have also found that T cells work better if they also put a protein that stimulates T cells called CD28. Investigators hope that adding the CD28 might also make the cells last for a longer time in the body. These CD19 chimeric receptor T cells with C28 T cells are investigational products not approved by the Food and Drug Administration. The purpose of this study is to find the biggest dose of chimeric T cells that is safe, to see how the T cell with this sort of chimeric receptor lasts, to learn what the side effects are and to see whether this therapy might help people with lymphoma or leukemia.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Feb 2009
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 21, 2007
CompletedFirst Posted
Study publicly available on registry
January 4, 2008
CompletedStudy Start
First participant enrolled
February 1, 2009
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2029
ExpectedFebruary 6, 2026
February 1, 2026
5.4 years
December 21, 2007
February 4, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Adverse Event Data per Patient
Evaluate the safety of autologous T-lymphocytes genetically modified to express CAR targeting CD19CAR in patients with NHL, ALL or B-CLL.
6 weeks
Secondary Outcomes (3)
Survival and function of CD19CAR T cells
15 years
Number of patients with tumor response
6 weeks
Correlation of additional doses and cumulative rise in the percentage of circulating gene modified cells
15 years
Study Arms (1)
CD19CAR-28-zeta T cells
EXPERIMENTALThree dose levels of CTLs will be evaluated. Each patient will receive one injection according to their assigned dose over 1-10 minutes IV. \*At the discretion of the attending physician, if after a 4 to 6-week evaluation period the patient has had apparent clinical benefit (as determined by symptoms, physical exam or radiological studies); repeat infusions separated by 4 to 6 weeks (up to a maximum of 3 extra doses) of modified T cells at the same dose level or below the patient's original dose can be administered.
Interventions
Intravenous injection Dose Level 1: CD19CAR-28zeta - 2x10\^7 cells/m\^2 Dose Level 2: CD19CAR-28zeta - 1 x10\^8 cells/m\^2 Dose Level 3: CD19CAR-28zeta - 2x10\^8 cells/m\^2
For patients with intermediate or low grade leukemia/lymphoma, patients may receive ipilimumab once during the week 2 visit after the T cell infusion.
Eligibility Criteria
You may qualify if:
- Patients must meet the following eligibility criteria to be included:
- Recurrent B cell lymphoma or leukemia (ALL or CLL), or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of intermediate B cell lymphoma with a treatment plan that will include high dose therapy and autologous stem cell transplantation. If a patient is less than 18, the lymphoma/leukemia is highly aggressive (i.e. lymphoblastic, Burkitt, ALL).
- Life expectancy of at least 12 weeks
- Recovered from the toxic effects of all prior chemotherapy before entering this study
- ANC greater than 500, HgB greater than 8.0
- Bilirubin less than 3 times the upper limit of normal
- AST less than 5 times the upper limit of normal
- Serum creatinine less than 3 times upper limit of normal
- Pulse oximetry of greater than 90% on room air
- Karnofsky/Lansky score of greater than 60%
- Available autologous transduced peripheral blood T-cells with greater than/=15% expression of CD19CAR determined by flow-cytometry
- Patients or legal guardians must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects. Patients or their guardians will be given a copy of the consent form
- Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 3 months after the study is concluded. The male partner should use a condom
You may not qualify if:
- History of hypersensitivity reactions to murine protein-containing products
- Pregnant or lactating
- Tumor in a location where enlargement could cause airway obstruction
- Currently receiving any investigational agents or have not received any tumor vaccines within the previous six weeks
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Houston Methodist Hospital
Houston, Texas, 77030, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
Related Publications (1)
Xu Y, Zhang M, Ramos CA, Durett A, Liu E, Dakhova O, Liu H, Creighton CJ, Gee AP, Heslop HE, Rooney CM, Savoldo B, Dotti G. Closely related T-memory stem cells correlate with in vivo expansion of CAR.CD19-T cells and are preserved by IL-7 and IL-15. Blood. 2014 Jun 12;123(24):3750-9. doi: 10.1182/blood-2014-01-552174. Epub 2014 Apr 29.
PMID: 24782509DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Carlos Ramos, MD
Baylor College of Medicine
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor
Study Record Dates
First Submitted
December 21, 2007
First Posted
January 4, 2008
Study Start
February 1, 2009
Primary Completion
July 1, 2014
Study Completion (Estimated)
July 1, 2029
Last Updated
February 6, 2026
Record last verified: 2026-02