B Cell LymphomaPhase 1CRETI-NHNCT00586391
CD19 Chimeric Receptor Expressing T Lymphocytes In B-Cell Non Hodgkin's Lymphoma, ALL & CLL
A Phase 1 study testing CD19CAR-28-zeta T cells and Ipilimumab in people with B Cell Lymphoma and Chronic Lymphocytic Leukemia, run by Baylor College of Medicine at 2 sites in United States.
Trial 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"). Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- B Cell Lymphoma, Chronic Lymphocytic Leukemia, Acute Lymphocytic Leukemia
- What is being tested?
- CD19CAR-28-zeta T cells and Ipilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 2 sitesUnited States
- Study dates
- Feb 2009to Jul 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Show all 13Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Houston Methodist Hospital
Houston, Texas, 77030
Texas Children's Hospital
Houston, Texas, 77030
About this study
Official title: Phase I Study Of CD19 Chimeric Receptor Expressing T Lymphocytes In B-Cell Non Hodgkin's Lymphoma, Acute Lymphocytic Leukemia, and Chronic Lymphocytic Leukemia
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.
Read more
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.
Read the detailed description
Patients will give us blood to make CD19 CD28 chimeric receptor-T cells in the laboratory. These cells will be grown and frozen for the patient. To make the T cells investigators take the blood and stimulate it with growth factors to make the T cells grow. To get the CD19 antibody (with CD28) to attach to the surface of the T cell, they insert the antibody gene into the T cell. This is done with a virus called a retrovirus that has been made for this study and will carry the antibody gene into the T cell. This virus also helps us find the T cells in the blood after they inject them using a special laboratory test. Because the patients will receive cells with a new gene in them they will be followed for a total of 15 years to see if there are any long term side effects of gene transfer. If the patient cannot visit the clinic, they may be contacted by the research coordinator or physician.
When the patients enroll on this study, they will be assigned a dose of CD19 CD28 chimeric receptor-T cells.
For those with intermediate or low grade lymphoma/leukemia: The investigators' studies so far have shown that the infused T cells may need to receive an extra boost in order to expand efficiently in the body. Therefore, 2 weeks after T cell infusion, the patient may receive one injection of a drug called ipilimumab, which they believe will help the T cells grow. This drug is approved by the FDA to treat certain cancers, such as melanoma, but the dose of drug used for this study will be lower than those used in those other treatments to avoid side effects.
Patients will be given an injection of cells into the vein through an IV at the assigned dose. The injection will take about 10 minutes. Patients will be followed in the clinic after the injection for up to 3 hours. If after a 4-6 week evaluation period after the infusion, the patient seems to be experiencing a benefit (confirmed by radiological studies, physical exam and/or symptoms), they may be able to receive up to three additional doses of the T cells if they wish. These additional infusions would be at least 4-6 weeks apart and at the same dose level they received the first time or a lower dose. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.
To learn more about the way the CD19 CD28 chimeric receptor-T cells are working and how long they last in the body, extra blood will be drawn.
- Being tested
- CD19CAR-28-zeta T cells, Ipilimumab
- Keywords
- B cell Lymphoma, Cancer, Chronic Lymphocytic Leukemia, CD19 CHIMERIC RECEPTOR EXPRESSING T LYMPHOCYTES, Acute Lymphocytic Leukemia
- Medical subject headings
- Lymphoma, B-Cell, Leukemia, Lymphocytic, Chronic, B-Cell, Precursor Cell Lymphoblastic Leukemia-Lymphoma, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD19CAR-28-zeta T cellsGenetic
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
IpilimumabDrug
Also called Yervoy
For patients with intermediate or low grade leukemia/lymphoma, patients may receive ipilimumab once during the week 2 visit after the T cell infusion.
| Study group | Role | What they receive |
|---|---|---|
| CD19CAR-28-zeta T cells | Experimental | Three 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. Receives: Genetic: CD19CAR-28-zeta T cells; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 weeks
Secondary outcomes (3)
Survival and function of CD19CAR T cells
survival will be measured by a real time Q-PCR assay to detect CD19.CAR T cells in peripheral blood from subjects. Plotts will be generated to depict patterns of survival. Function will be assessed by assays.
Measured: 15 years
Number of patients with tumor response
To measure the anti-tumor effects of chimeric CD19 receptor transduced autologous T- lymphocytes in patients with Low-grade non-Hodgkin's Lymphoma (NHL) and Leukemia
Measured: 6 weeks
Correlation of additional doses and cumulative rise in the percentage of circulating gene modified cells
To discover if the clinical and laboratory data collected following the additional doses of cells are consistent with a cumulative rise in the percentage of circulating gene modified cells and if the infusions are associated with sequential reductions in patient disease burden.
Measured: 15 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2008 (estimated)
- Study startFeb 2009
- Primary completionJul 2014
- Study completionJul 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for B Cell LymphomaStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Responsible party
- Principal investigator, Helen Heslop, Baylor College of Medicine
- Investigators
- Helen Heslop, MD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00586391
- Sponsor's protocol ID
- 19384-CRETI-NH
- Acronym
- CRETI-NH
- Status last verified
- Sep 2026
- First submitted
- 21 Dec 2007
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 24782509
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study Of CD19 Chimeric Receptor Expressing T Lymphocytes In B-Cell Non Hodgkin's Lymphoma, Acute Lymphocytic Leukemia, and Chronic Lymphocytic Leukemia
- ClinicalTrials.gov ID
- NCT00586391
- Acronym / sponsor ID
- CRETI-NH / 19384-CRETI-NH
- Keywords
- B cell Lymphoma, Cancer, Chronic Lymphocytic Leukemia, CD19 CHIMERIC RECEPTOR EXPRESSING T LYMPHOCYTES, Acute Lymphocytic Leukemia
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine
- Study start
- Feb 2009
- Primary completion
- Jul 2014 (actual)
- Study completion
- Jul 2029 (estimated)
- First posted
- 4 Jan 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Patients will give us blood to make CD19 CD28 chimeric receptor-T cells in the laboratory. These cells will be grown and frozen for the patient. To make the T cells investigators take the blood and stimulate it with growth factors to make the T cells grow. To get the CD19 antibody (with CD28) to attach to the surface of the T cell, they insert the antibody gene into the T cell. This is done with a virus called a retrovirus that has been made for this study and will carry the antibody gene into the T cell. This virus also helps us find the T cells in the blood after they inject them using a special laboratory test. Because the patients will receive cells with a new gene in them they will be followed for a total of 15 years to see if there are any long term side effects of gene transfer. If the patient cannot visit the clinic, they may be contacted by the research coordinator or physician.
When the patients enroll on this study, they will be assigned a dose of CD19 CD28 chimeric receptor-T cells.
For those with intermediate or low grade lymphoma/leukemia: The investigators' studies so far have shown that the infused T cells may need to receive an extra boost in order to expand efficiently in the body. Therefore, 2 weeks after T cell infusion, the patient may receive one injection of a drug called ipilimumab, which they believe will help the T cells grow. This drug is approved by the FDA to treat certain cancers, such as melanoma, but the dose of drug used for this study will be lower than those used in those other treatments to avoid side effects.
Patients will be given an injection of cells into the vein through an IV at the assigned dose. The injection will take about 10 minutes. Patients will be followed in the clinic after the injection for up to 3 hours. If after a 4-6 week evaluation period after the infusion, the patient seems to be experiencing a benefit (confirmed by radiological studies, physical exam and/or symptoms), they may be able to receive up to three additional doses of the T cells if they wish. These additional infusions would be at least 4-6 weeks apart and at the same dose level they received the first time or a lower dose. The treatment will be given by the Center for Cell and Gene Therapy at Texas Children's Hospital or Houston Methodist Hospital.
To learn more about the way the CD19 CD28 chimeric receptor-T cells are working and how long they last in the body, extra blood will be drawn.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CD19CAR-28-zeta T cells | Experimental | Genetic: CD19CAR-28-zeta T cells, Drug: IpilimumabThree 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. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (13 listed)
- 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
Key exclusion criteria (4 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CD19CAR-28-zeta T cellsIntravenous 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 | Genetic | CD19CAR-28-zeta T cells |
| IpilimumabAlso: YervoyFor patients with intermediate or low grade leukemia/lymphoma, patients may receive ipilimumab once during the week 2 visit after the T cell infusion. | Drug | CD19CAR-28-zeta T cells |
Primary outcome
Adverse Event Data per Patient
Time frame: 6 weeks
Evaluate the safety of autologous T-lymphocytes genetically modified to express CAR targeting CD19CAR in patients with NHL, ALL or B-CLL.
3 secondary outcomes
Survival and function of CD19CAR T cells
Time frame: 15 years
Number of patients with tumor response
Time frame: 6 weeks
Correlation of additional doses and cumulative rise in the percentage of circulating gene modified cells
Time frame: 15 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2026.
- Derived from this study: PubMed 24782509Xu 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.
Related trials for B Cell Lymphoma
Not yet recruitingPhase 1/2
A Study of Sonrotoclax (BGB-11417) in Children With Relapsed or Refractory Acute Myeloid Leukemia and B-cell Acute Lymphoblastic Leukemia
Relapsed Acute Myeloid Leukemia, Refractory Acute Myeloid Leukemia
RecruitingPhase 1
Anti-CRLF2-R/TSLPR Chimeric Antigen Receptor T Cells (TSLPR-CART) in Participants With Recurrent or Refractory CRLF2-R/TSLPR-Overexpressing B-Cell Acute Lymphoblastic Leukemia (B-ALL)
B-All, Acute Lymphoblastic Leukemia
RecruitingPhase 2
CD22 CAR T-cells to Extend Remission Following Commercial CD19 CAR T-cells in Children, Adolescents, and Adults With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia
Acute Lymphoblastic Leukemia, B-All
RecruitingPhase 1
Testing the Combination of Anti-cancer Drugs Mosunetuzumab, Polatuzumab Vedotin, and Lenalidomide for the Treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma
Diffuse Large B-Cell Lymphoma, Not Otherwise Specified, High Grade B-Cell Lymphoma
RecruitingPhase 2
Testing the Combination of Venetoclax and Rituximab, in Comparison to the Usual Treatment (Ibrutinib Plus Rituximab or Zanubrutinib Alone) for Waldenstrom's Macroglobulinemia/Lymphoplasmacytic Lymphoma
Lymphoplasmacytic Lymphoma, Waldenstrom Macroglobulinemia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Helen Heslop, MD principal investigator
Baylor College of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing CD19CAR-28-zeta T cells and Ipilimumab in people with B Cell Lymphoma and Chronic Lymphocytic Leukemia, run by Baylor College of Medicine at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 2 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Event Data per Patient (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00586391, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2026.