Non-Hodgkin's LymphomaPhase 1NCT01316146
Administration of T Lymphocytes for Hodgkin's Lymphoma and Non-Hodgkin's Lymphoma (CART CD30)
A Phase 1 study testing CAR.CD30 T cells in people with Non-Hodgkin's Lymphoma and Hodgkin's Lymphoma, run by UNC Lineberger Comprehensive Cancer Center at 3 sites in United States.
Trial summary
The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from diseases caused by germs or toxic substances. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma
- What is being tested?
- CAR.CD30 T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 3 sitesUnited States
- Study dates
- 3 Oct 2011to 4 May 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Procurement Inclusion Criteria:
- Referred patients will initially be consented for procurement of blood for generation of the transduced ATL. Eligibility criteria at this stage include:
- Diagnosis of recurrent CD30+ HL or CD30+ NHL, or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of relapsed/refractory CD30+ HL or CD30+ NHL with a treatment plan that will include high dose therapy and stem cell transplantation
- CD30 positive tumor (result can be pending at this time)
- Hgb > 8.0
- Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
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- Karnofsky or Lansky score greater than 60%
- Procurement Exclusion Criteria
- Active infection with HIV, HTLV, HBV, HCV (can be pending at this time).
- Treatment Inclusion Criteria:
- Diagnosis - CD30+ HL or CD30+ NHL:
- During the Dose Escalation Phase: only adult patients with active disease failing standard therapy
- After Dose Escalation: any patient (children or adults) newly diagnosed, unable to receive or complete standard therapy OR diagnosis of relapsed/refractory CD30+ HL or CD30+ NHL with a treatment plan that will include high dose therapy and autologous stem cell transplantation. (During dose escalation: only adult patients (age 18 and older; After Dose Escalation: any patient (children ages 0-17 or adults)
- CD30 positive tumor
- Bilirubin 1.5 times or less than upper limit of normal.
- AST 3 times or less than upper limit of normal.
- Serum creatinine 1.5 times or less than upper limit of normal.
- Pulse oximetry of > 90% on room air
- Karnofsky or Lansky score of > 60%.
- Available autologous T cells with 15% or more expression of CD30CAR determined by flow-cytometry.
- Recovered from acute toxic effects of all prior chemotherapy at least one week and 30 days from prior chemotherapy before entering this study
- Adequate pulmonary function with FEV1, FVC and DLCO greater than or equal to 50% of expected corrected for hemoglobin.
- Sexually active patients must be willing to utilize one of the more effective birth control methods during the study and for 6 months after the study is concluded. The male partner should use a condom.
- 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.
Who cannot join
- Procurement Exclusion Criteria:
- Active infection with HIV, HTLV, HBV, HCV (can be pending at this time).
- Treatment Exclusion Criteria:
- Currently receiving any investigational agents or received any tumor vaccines within the previous six weeks.
- Received anti-CD30 antibody-based therapy within the previous 4 weeks.
- History of hypersensitivity reactions to murine protein-containing products.
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- Pregnant or lactating.
- Tumor in a location where enlargement could cause airway obstruction.
- Current use of systemic corticosteroids.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of North Carolina Chapel Hill
Chapel Hill, North Carolina, 27599
Houston Methodist Hospital
Houston, Texas, 77030
Texas Children's Hospital
Houston, Texas, 77030
About this study
Official title: Phase I Study of the Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor for Relapsed CD30+ Hodgkin's Lymphoma and CD30+ Non-Hodgkin's Lymphoma (CART CD30)
The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from diseases caused by germs or toxic substances. They work by binding those germs or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected with germs. Both antibodies and T cells have been used to treat patients with cancers: they both have shown promise, but have not been strong enough to cure most patients. Investigators hope that both will work better together.
Investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. Investigators now want to see if they can attach a gene to T cells that will help them do a better job at recognizing and killing lymphoma cells.
Read more
The new gene that investigators will put in T cells makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma, but have not been strong enough to cure most patients.
For this study, the anti-CD30 antibody 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. These CD30 chimeric receptor-activated T cells seem to kill some of the tumor, but they don't last very long and so their chances of fighting the cancer are unknown.
Read the detailed description
When the patient enrolls on this study, they will be assigned a dose of CD30 chimeric receptor-activated T cells. The dose level of cells that they will receive will not be based on a medical determination of what is best for the patient, instead the dose is based on the order in which the patient enrolled on the study relative to other participants. Subjects enrolled earlier in the study will receive a lower dose of cells than those enrolled later in the study. The risks of harm and discomfort from the study treatment may bear some relationship to the dose level. The potential for direct benefit, if any, may also vary with the dose level.
The patient will be given an injection of CD30 chimeric receptor-activated T cells into the vein through an IV line at the assigned dose. The injection will take 1-10 minutes. Investigators will follow the subject in the clinic after the injection for up to 4 hours.
To learn more about the way the CD30 chimeric receptor-activated T cells are working and how long they last in the body, extra blood will be drawn.
If the patient has stable disease (the lymphoma did not grow) or there is a reduction in the size of the lymphoma on imaging studies after the T-cell infusion, s/he can receive up to six additional doses of the T cells at 8 to 12 weeks intervals if s/he wishes. After each T-cell infusion, s/he will be monitored as described above.
- Conditions
- Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma
- Being tested
- CAR.CD30 T cells
- Keywords
- Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Lymphoma, T lymphocytes
- Medical subject headings
- Lymphoma, Non-Hodgkin, Hodgkin Disease, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CAR.CD30 T cellsDrug
Three dose levels will be evaluated:
Group One, 2x10^7 cells/m^2
Group Two, 1x10^8 cells/m^2
Group Three, 2x10^8 cells/m^2;
Cell Administration: CAR+ ATL will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line. The expected volume will be 1-50cc.
| Study group | Role | What they receive |
|---|---|---|
| CAR.CD30 T cells | Experimental | Three dose levels will be evaluated. Using the modified continual reassessment method, cohorts of size two will be enrolled at each dose level. Each patient will receive one injection (IV) according to the dosing schedules: starting with the lowest cell dose (2×10^7 cells/m2) and then escalate the cell dose to the highest cell dose (2×10^8/m2) as per study design. Receives: Drug: CAR.CD30 T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with adverse events as a measure of safety and tolerability of escalating doses of autologous activated T lymphocytes
To evaluate the safety of escalating doses of autologous activated T lymphocytes (ATL), genetically modified to express an artificial chimeric antigen receptor (CAR) that targets the CD30 molecule (CAR.CD30) and also contains the CD28 endodomain, in patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL).
Measured: 6 weeks
Secondary outcomes (2)
Measure the survival of CAR.CD30 in vivo
To measure the survival of CAR.CD30 transduced ATL in vivo.
Measured: 15 years
Measure the response of the subjects tumor to the CAR.CD30 transduced ATL
To measure the anti-tumor effects of CAR.CD30 transduced ATL in patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL).
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 posted16 Mar 2011 (estimated)
- Study start3 Oct 2011
- Primary completion28 Jan 2016
- Study completion4 May 2022
Why it stopped: Study never truly opened to accrual at UNC. Study and data were transfered to UNC as the IND for the study was transfered to UNC. IRB closed the study.
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 Non-Hodgkin's LymphomaStudies of the same condition, open and under way.
- More trials run by UNC Lineberger Comprehensive Cancer CenterThe 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
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Baylor College of Medicine, Center for Cell and Gene Therapy, Baylor College of Medicine
- Responsible party
- Sponsor
- Investigators
- Barbara Savoldo, MD, PhD, Principal investigator, University of North Carolina, Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01316146
- Sponsor's protocol ID
- LCCC 1544-ATL
- Other IDs
- H-27721-CART CD30
- Status last verified
- Mar 2023
- First submitted
- 4 Mar 2011
- Last updated
- 22 Mar 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ramos CA, Ballard B, Zhang H, Dakhova O, Gee AP, Mei Z, Bilgi M, Wu MF, Liu H, Grilley B, Bollard CM, Chang BH, Rooney CM, Brenner MK, Heslop HE, Dotti G, Savoldo B. Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes. J Clin Invest. 2017 Sep 1;127(9):3462-3471. doi: 10.1172/JCI94306. Epub 2017 Aug 14.
PubMed 28805662
Study at a glance
From the registry record, last updated by the sponsor on 22 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of the Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor for Relapsed CD30+ Hodgkin's Lymphoma and CD30+ Non-Hodgkin's Lymphoma (CART CD30)
- ClinicalTrials.gov ID
- NCT01316146
- Acronym / sponsor ID
- LCCC 1544-ATL
- Conditions
- Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma
- Keywords
- Hodgkin's Lymphoma, Non-Hodgkin's Lymphoma, Lymphoma, T lymphocytes
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Study never truly opened to accrual at UNC. Study and data were transfered to UNC as the IND for the study was transfered to UNC. IRB closed the study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Baylor College of Medicine, Center for Cell and Gene Therapy, Baylor College of Medicine
- Study start
- 3 Oct 2011 (actual)
- Primary completion
- 28 Jan 2016 (actual)
- Study completion
- 4 May 2022 (actual)
- First posted
- 16 Mar 2011 (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.
The body has different ways of fighting infection and disease. No single way seems perfect for fighting cancer. This research study combines two different ways of fighting disease: antibodies and T cells. Antibodies are proteins that protect the body from diseases caused by germs or toxic substances. They work by binding those germs or substances, which stops them from growing and causing bad effects. T cells, also called T lymphocytes, are special infection-fighting blood cells that can kill other cells, including tumor cells or cells that are infected with germs. Both antibodies and T cells have been used to treat patients with cancers: they both have shown promise, but have not been strong enough to cure most patients. Investigators hope that both will work better together.
Investigators have found from previous research that they can put a new gene into T cells that will make them recognize cancer cells and kill them. Investigators now want to see if they can attach a gene to T cells that will help them do a better job at recognizing and killing lymphoma cells.
The new gene that investigators will put in T cells makes an antibody called anti-CD30. This antibody sticks to lymphoma cells because of a substance on the outside of the cells called CD30. Anti-CD30 antibodies have been used to treat people with lymphoma, but have not been strong enough to cure most patients.
For this study, the anti-CD30 antibody 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. These CD30 chimeric receptor-activated T cells seem to kill some of the tumor, but they don't last very long and so their chances of fighting the cancer are unknown.
Detailed description
When the patient enrolls on this study, they will be assigned a dose of CD30 chimeric receptor-activated T cells. The dose level of cells that they will receive will not be based on a medical determination of what is best for the patient, instead the dose is based on the order in which the patient enrolled on the study relative to other participants. Subjects enrolled earlier in the study will receive a lower dose of cells than those enrolled later in the study. The risks of harm and discomfort from the study treatment may bear some relationship to the dose level. The potential for direct benefit, if any, may also vary with the dose level.
The patient will be given an injection of CD30 chimeric receptor-activated T cells into the vein through an IV line at the assigned dose. The injection will take 1-10 minutes. Investigators will follow the subject in the clinic after the injection for up to 4 hours.
To learn more about the way the CD30 chimeric receptor-activated T cells are working and how long they last in the body, extra blood will be drawn.
If the patient has stable disease (the lymphoma did not grow) or there is a reduction in the size of the lymphoma on imaging studies after the T-cell infusion, s/he can receive up to six additional doses of the T cells at 8 to 12 weeks intervals if s/he wishes. After each T-cell infusion, s/he will be monitored as described above.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR.CD30 T cells | Experimental | Drug: CAR.CD30 T cellsThree dose levels will be evaluated. Using the modified continual reassessment method, cohorts of size two will be enrolled at each dose level. Each patient will receive one injection (IV) according to the dosing schedules: starting with the lowest cell dose (2×10^7 cells/m2) and then escalate the cell dose to the highest cell dose (2×10^8/m2) as per study design. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (24 listed)
- Referred patients will initially be consented for procurement of blood for generation of the transduced ATL. Eligibility criteria at this stage include:
- Diagnosis of recurrent CD30+ HL or CD30+ NHL, or newly diagnosed patients unable to receive or complete standard therapy OR diagnosis of relapsed/refractory CD30+ HL or CD30+ NHL with a treatment plan that will include high dose therapy and stem cell transplantation
- CD30 positive tumor (result can be pending at this time)
- Hgb > 8.0
- Informed consent explained to, understood by and signed by patient/guardian. Patient/guardian given copy of informed consent.
Key exclusion criteria (9 listed)
- Active infection with HIV, HTLV, HBV, HCV (can be pending at this time).
- Currently receiving any investigational agents or received any tumor vaccines within the previous six weeks.
- Received anti-CD30 antibody-based therapy within the previous 4 weeks.
- History of hypersensitivity reactions to murine protein-containing products.
- Pregnant or lactating.
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 |
|---|---|---|
| CAR.CD30 T cellsThree dose levels will be evaluated: Group One, 2x10^7 cells/m^2 Group Two, 1x10^8 cells/m^2 Group Three, 2x10^8 cells/m^2; Cell Administration: CAR+ ATL will be given by intravenous injection over 1-10 minutes through either a peripheral or a central line. The expected volume will be 1-50cc. | Drug | CAR.CD30 T cells |
Primary outcome
Number of participants with adverse events as a measure of safety and tolerability of escalating doses of autologous activated T lymphocytes
Time frame: 6 weeks
To evaluate the safety of escalating doses of autologous activated T lymphocytes (ATL), genetically modified to express an artificial chimeric antigen receptor (CAR) that targets the CD30 molecule (CAR.CD30) and also contains the CD28 endodomain, in patients with CD30+ refractory/relapsed Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL).
2 secondary outcomes
Measure the survival of CAR.CD30 in vivo
Time frame: 15 years
Measure the response of the subjects tumor to the CAR.CD30 transduced ATL
Time frame: 15 years
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Mar 2023.
- Derived from this study: PubMed 28805662Ramos CA, Ballard B, Zhang H, Dakhova O, Gee AP, Mei Z, Bilgi M, Wu MF, Liu H, Grilley B, Bollard CM, Chang BH, Rooney CM, Brenner MK, Heslop HE, Dotti G, Savoldo B. Clinical and immunological responses after CD30-specific chimeric antigen receptor-redirected lymphocytes. J Clin Invest. 2017 Sep 1;127(9):3462-3471. doi: 10.1172/JCI94306. Epub 2017 Aug 14.
- Individual participant dataSharing planned: No
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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.
Barbara Savoldo, MD, PhD principal investigator
University of North Carolina, Chapel Hill
3 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 CAR.CD30 T cells in people with Non-Hodgkin's Lymphoma and Hodgkin's Lymphoma, run by UNC Lineberger Comprehensive Cancer Center at 3 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 24 inclusion and 9 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: withdrawn, as of the sponsor's last update on 22 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Number of participants with adverse events as a measure of safety and tolerability of escalating doses of autologous activated T lymphocytes (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 NCT01316146, 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 22 Mar 2023.