CD19 Chimeric Receptor Expressing T Lymphocytes In B-Cell Non Hodgkin's Lymphoma And Chronic Lymphocytic Leukemia (CRETI-NH)
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Purpose
Patients on this study have a type of lymph gland cancer called non-Hodgkin Lymphoma or chronic Lymphocytic Leukemia (these 2 diseases will be referred to as "Lymphoma" or "CLL"). Their lymphoma or CLL has come back or has not gone away after treatment (including the best treatment we know for these cancers). Because there is no standard treatment for the cancer at this time, patients are being asked to volunteer to be in a gene transfer research study using special immune cells. Patients may have already thought a lot about being in this study. They may even have already made a decision about whether to be in the study. Even if this is true for the patient, it is important that we give the patients this information and talk about it before we start in the study.
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 lymphoma cells because of a substance on the outside of these cells called CD19. CD19 antibodies have been used to treat people with lymphoma and CLL. 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, we have also found that T cells work better if we also put a protein that stimulates T cells called CD28. We hope that adding the CD28 might also make the cells last for a longer time in the body.
In this study we are going to see if this is true by putting the CD19 chimeric receptor alone into half the cells and the CD19 chimeric receptor with CD28 into the other half. We will then be able to see if there is a difference in how long they last. These CD19 chimeric receptor T cells and CD19 chimeric receptor with C28 T cells are investigational products not approved by the Food and Drug Administration.
| Condition | Intervention | Phase |
|---|---|---|
|
B Cell Lymphoma Chronic Lymphocytic Leukemia |
Genetic: CD19CAR-zeta and CD19CAR-28-zeta T cells Drug: Ipilimumab |
Phase 1 |
| Study Type: | Interventional |
| Study Design: | Endpoint Classification: Safety Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Phase I Study Of CD19 Chimeric Receptor Expressing T Lymphocytes In B-Cell Non Hodgkin's Lymphoma And Chronic Lymphocytic Leukemia |
- Evaluate the safety of autologous T-lymphocytes genetically modified to express CAR targeting CD19CAR in patients with refractory/relapsed NHL or B-CLL. [ Time Frame: 6 weeks ] [ Designated as safety issue: Yes ]
- Measure the survival and function of CD19CAR T cells in vivo [ Time Frame: 15 years ] [ Designated as safety issue: No ]
- To compare two different T-cell products in the same patient in which the CD19CAR will differ only by the inclusion of the CD28 co-stimulatory endodomain. [ Time Frame: 15 years ] [ Designated as safety issue: No ]
- To measure the anti-tumor effects of chimeric CD19 receptor transduced autologous T- lymphocytes in patients with Low-grade non-Hodgkin's Lymphoma (NHL) or Chronic Lymphocytic leukemia (B-CLL). [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 18 |
| Study Start Date: | February 2009 |
| Estimated Study Completion Date: | February 2033 |
| Estimated Primary Completion Date: | February 2018 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: CD19CAR-zeta and CD19CAR-28-zeta T cells
Intravenous injection* over 1 to 10 minutes Dose Level 1: CD19CAR - 2x10^7 cells/m^2 CD19CAR-28 - 2x10^7 cells/m^2 Dose Level 2: CD19CAR - 1x10^8 cells/m^2 CD19CAR-28 - 1 x10^8 cells/m^2 Dose Level 3: CD19CAR - 2x10^8 cells/m^2 CD19CAR-28 - 2x10^8 cells/m^2 *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. |
Genetic: CD19CAR-zeta and CD19CAR-28-zeta T cells
Intravenous injection over 1 to 10 minutes Dose Level 1: CD19CAR - 2x10^7 cells/m^2 CD19CAR-28 - 2x10^7 cells/m^2 Dose Level 2: CD19CAR - 1x10^8 cells/m^2 CD19CAR-28 - 1 x10^8 cells/m^2 Dose Level 3: CD19CAR - 2x10^8 cells/m^2 CD19CAR-28 - 2x10^8 cells/m^2 Other Names:
Drug: Ipilimumab
Patients will receive ipilimumab once during the week 2 visit after the T cell infusion.
Other Name: Yervoy
|
Show Detailed Description Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
INCLUSION CRITERIA:
Patients must meet the following eligibility criteria to be included:
- Recurrent low grade or intermediate grade B cell lymphoma or CLL, or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of relapsed refractory intermediate B cell lymphoma with a treatment plan that will include high dose therapy and autologous stem cell transplantation
- 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
EXCLUSION CRITERIA:
- 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
Contacts and Locations| Contact: Carlos Ramos, MD | 832-824-4817 | caramos@txch.org |
| Contact: Vicky Torrano | 832-824-7821 | vxtorran@txch.org |
| United States, Texas | |
| Texas Children's Hospital | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Carlos Ramos, MD 832-824-4817 caramos@txch.org | |
| Methodist Hospital | Recruiting |
| Houston, Texas, United States, 77030 | |
| Contact: Carlos Ramos, MD 832-824-4817 caramos@txch.org | |
| Principal Investigator: | Carlos Ramos, MD | Baylor College of Medicine |
More Information
No publications provided
| Responsible Party: | Carlos Ramos, Assistant Professor, Baylor College of Medicine |
| ClinicalTrials.gov Identifier: | NCT00586391 History of Changes |
| Obsolete Identifiers: | NCT00608270 |
| Other Study ID Numbers: | 19384-CRETI-NH |
| Study First Received: | December 21, 2007 |
| Last Updated: | January 8, 2013 |
| Health Authority: | United States: Food and Drug Administration United States: Institutional Review Board |
Keywords provided by Baylor College of Medicine:
|
B cell Lymphoma Cancer Chronic Lymphocytic Leukemia CD19 CHIMERIC RECEPTOR EXPRESSING T LYMPHOCYTES |
Additional relevant MeSH terms:
|
Leukemia Leukemia, Lymphocytic, Chronic, B-Cell Leukemia, Lymphoid Lymphoma Lymphoma, Non-Hodgkin Lymphoma, B-Cell Neoplasms by Histologic Type |
Neoplasms Leukemia, B-Cell Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases |
ClinicalTrials.gov processed this record on May 16, 2013