Ignite Creation Date:
2025-12-24 @ 6:30 PM
Ignite Modification Date:
2025-12-30 @ 1:44 AM
Study NCT ID:
NCT03602157
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-12-08
First Post:
2018-07-17
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Study of CAR-T Cells Expressing CD30 and CCR4 for r/r CD30+ HL and CTCL
Sponsor:
UNC Lineberger Comprehensive Cancer Center
Organization:
Study Overview
Official Title:
Phase I Study of the Administration of T Lymphocytes Co-Expressing the CD30 Chimeric Antigen Receptor (CAR) and CCR4 for Relapsed/Refractory CD30+ Hodgkin Lymphoma and Cutaneous T-Cell Lymphoma
Status:
ACTIVE_NOT_RECRUITING
Status Verified Date:
2025-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The body has different ways of fighting infection and disease. No single way is 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 disease caused by bacteria or toxic substances. Antibodies work by binding bacteria 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 bacteria or viruses. Both antibodies and T cells have been used to treat patients with cancers. They both have shown promise, but neither alone has been sufficient to treat cancer. This study will combine both T cells and antibodies in order to create a more effective treatment called Autologous T Lymphocyte Chimeric Antigen Receptor cells targeted against the CD30 antigen (ATLCAR.CD30). Another treatment being tested includes the Autologous T Lymphocyte Chimeric Antigen Receptor cells targeted against the CD30 antigen with CCR4 (ATLCAR.CD30.CCR4) to help the cells move to regions in the patient's body where the cancer is present. Participants in this study will receive either ATLCAR.CD30.CCR4 cells alone or will receive ATLCAR.CD30.CCR4 cells combined with ATLCAR.CD30 cells.
Previous studies have shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. The new gene that is put in the T cells in this study 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 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 (combination) receptor-activated T cells (ATLCAR.CD30) can kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown.
Researchers are working to identify ways to improve the ability of ATLCAR.CD30 to destroy tumor cells. T cells naturally produce a protein called CCR4 which functions as a navigation system directing T cells toward tumor cells specifically. In this study, researchers will also genetically modify ATLCAR.CD30 cells to produce more CCR4 proteins and they will be called ATLCAR.CD30.CCR4. The study team believes that the ATLCAR.CD30.CCR4 cells will be guided directly toward the tumor cells based on their navigation system. In addition, the study team believes the majority of ATLCAR.CD30 cells will also be guided directly toward tumor cells when given together with ATLCAR.CD30.CCR4, increasing their anti-cancer fighting ability.
This is the first time ATLCAR\>CD30.CCR4 cells or combination of ATLCAR.CD30.CCR4 and ATLCAR.CD30 cells are used to treat lymphoma. The purpose of this study to determine the following:
* What is the safe dose of ATLCAR.CD30.CCR4 cells to give to patients
* What is the safe dose of the combination of ATLCAR.CD30 and ATLCAR.CD30.CCR4 cells to give to patients
Previous studies have shown that a new gene can be put into T cells that will increase their ability to recognize and kill cancer cells. The new gene that is put in the T cells in this study 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 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 (combination) receptor-activated T cells (ATLCAR.CD30) can kill some of the tumor, but they do not last very long in the body and so their chances of fighting the cancer are unknown.
Researchers are working to identify ways to improve the ability of ATLCAR.CD30 to destroy tumor cells. T cells naturally produce a protein called CCR4 which functions as a navigation system directing T cells toward tumor cells specifically. In this study, researchers will also genetically modify ATLCAR.CD30 cells to produce more CCR4 proteins and they will be called ATLCAR.CD30.CCR4. The study team believes that the ATLCAR.CD30.CCR4 cells will be guided directly toward the tumor cells based on their navigation system. In addition, the study team believes the majority of ATLCAR.CD30 cells will also be guided directly toward tumor cells when given together with ATLCAR.CD30.CCR4, increasing their anti-cancer fighting ability.
This is the first time ATLCAR\>CD30.CCR4 cells or combination of ATLCAR.CD30.CCR4 and ATLCAR.CD30 cells are used to treat lymphoma. The purpose of this study to determine the following:
* What is the safe dose of ATLCAR.CD30.CCR4 cells to give to patients
* What is the safe dose of the combination of ATLCAR.CD30 and ATLCAR.CD30.CCR4 cells to give to patients
Detailed Description:
This study is a single center, open-label Phase I clinical trial designed to determine the safety of escalating doses of autologous activated T lymphocytes (ATLs) co-expressing the chimeric antigen receptor specific for the CD30 antigen and the CCR4 chemokine receptor (ATLCAR.CD30.CCR4) in subjects with relapsed/refractory CD30+ Hodgkin (HL) and cutaneous T Cell Lymphoma (CTCL). Subjects with grey zone lymphoma will also be eligible to enroll on this protocol; the characteristics of grey zone lymphoma are very similar to HL and therefore will be referred to collectively throughout the protocol under the general term of HL. Subjects will receive either ATLCAR.CD30.CCR4 or the ATLCAR.CD30.CCR4 product in combination with an ATL product encoding only the CAR.CD30 (ATLCAR.CD30). The dose for ATLCAR.CD30 will be fixed at the highest dose level as this product has been shown to be safe in phase I trials with and without lymphodepletion. Six total dose levels of ATLCAR.CD30.CCR4 with or without ATLCAR.CD30 will be tested. Prior to receiving the infusions, subjects will undergo lymphodepletion with bendamustine and fludarabine, The 3+3 design will be used for estimating the maximum tolerated dose (MTD) of ATLCAR.CD30.CCR4 in combination with ATLCAR.CD30. Any dose level may be expanded to 4-9 subjects to explore adverse events (AEs) of special interest prior to moving to the next dose level. If due to the expansion ≥1/3 of the total number of subject on that dose level experiences a DLT, the study would not escalate to the next highest dose level and the maximum tolerated dose would be exceeded. The final MTD will be the highest dose of ATLCAR.CD30.CCR4 and ATLCAR.CD30 with observed DLT rate of less than 1/3. An expansion cohort will enroll up to 8 subjects at the MTD of ATLCAR.CD30.CCR4 and ATLCAR.CD30 to further assess safety and efficacy of these cellular products. Secondary endpoints include evaluation of persistence of ATLCAR.CD30.CCR4 vs. ATLCAR.CD30 in the peripheral blood, accumulation of ATLCAR.CD30.CCR4 vs. ATLCAR.CD30 in tumor biopsies, and progression free survival (PFS).
LCCC1606-ATL builds on LCCC1532-ATL, a phase Ib/II trial investigating the safety and efficacy of ATLCAR.CD30 in subjects with CD30+ lymphoma.
OUTLINE
Cell Procurement
Up to 300 mL total of peripheral blood will be obtained (in up to 3 collections) from subjects for cell procurement. Up to 300 mL total of peripheral blood will be obtained (in up to 3 collections) from subjects for cell procurement. Additionally, leukapheresis may be performed to isolate sufficient cells in subjects with a low absolute lymphocyte count or who had inadequate peripheral blood collection. The parameters for apheresis will be up to 2 blood volumes. Collected peripheral blood may be used for generation of CAR-T cells if the cells were collected on another CAR-T cell trial for which Lineberger Comprehensive Cancer Center is the sponsor and if the subject is eligible for procurement/screening on the LCCC 1606-ATL protocol. ATLCAR.CD30 cells manufactured for a different protocol may be used for LCCC 1606-ATL, if they fit specifications for the protocol and the patient qualifies for the protocol.
Lymphodepletion Regimen
In order to receive lymphodepletion and CAR-T cells, subjects must still have evidence of active disease.
All subjects will receive lymphodepletion with bendamustine 70 mg/m2 and fludarabine 30 mg/m2 for 3 days to reduce possible toxicity associated with the agent prior to administration of CAR-T cells.
NOTE: Any subject who tests positive for Hepatitis B core antibody and negative for Hepatitis B viral load during screening must initiate an anti-Hepatitis B prophylaxis regimen prior to lymphodepletion.
Bendamustine and fludarabine will be administered concomitantly for lymphodepletion (i.e., intravenous (IV) administration of bendamustine 70 mg/m2/day over 3 consecutive days and IV fludarabine 30 mg/m2/day over 3 consecutive days) prior to the first CAR-T cell infusion. Bendamustine should be administered first followed by IV administration of fludarabine.
Cell Administration
ATLCAR.CD30.CCR4 with or without ATLCAR.CD30 cells will be given to eligible subjects 2-14 days (preferably 2-4 days) after lymphodepletion with fludarabine and bendamustine. The dose of cells will vary, depending on the cohort enrolled. The cells will be administered by a licensed provider (oncology nurse or physician) via intravenous injection over 1-10 minutes through either a peripheral or a central line. The expected volume will be 1-50cc. Subjects in the dose expansion part of the study who received the highest safe dose level of ATLCAR.CD30 and ATLCAR.CD30.CCR4 may receive a second infusion of ATLCAR.CD30 and ATLCAR.CD30.CCR4 if cells are available equal to the dose administered for the first cell infusion (or a lower dose).
Duration of Therapy
Therapy in LCCC1606-ATL involves one to two infusion(s) of ATLCAR.CD30.CCR4 with or without ATLCAR.CD30 cells. Treatment with one infusion will be administered unless:
* Subject decides to withdraw from study treatment, OR
* General or specific changes in the subject's condition render the subject unacceptable for further treatment in the judgment of the investigator.
Duration of Follow-up
Subjects who receive a cell infusion will be followed for up to 15 years for replication competent retrovirus (RCR) evaluation or until death, whichever occurs first. Subjects who are removed from study and do not receive the cellular therapy product due to unacceptable adverse events will be followed until resolution or stabilization of the adverse event. Subjects who have progressive disease or initiate another cancer therapy after receiving a cell infusion(s) will still be required to complete abbreviated follow up procedures.
LCCC1606-ATL builds on LCCC1532-ATL, a phase Ib/II trial investigating the safety and efficacy of ATLCAR.CD30 in subjects with CD30+ lymphoma.
OUTLINE
Cell Procurement
Up to 300 mL total of peripheral blood will be obtained (in up to 3 collections) from subjects for cell procurement. Up to 300 mL total of peripheral blood will be obtained (in up to 3 collections) from subjects for cell procurement. Additionally, leukapheresis may be performed to isolate sufficient cells in subjects with a low absolute lymphocyte count or who had inadequate peripheral blood collection. The parameters for apheresis will be up to 2 blood volumes. Collected peripheral blood may be used for generation of CAR-T cells if the cells were collected on another CAR-T cell trial for which Lineberger Comprehensive Cancer Center is the sponsor and if the subject is eligible for procurement/screening on the LCCC 1606-ATL protocol. ATLCAR.CD30 cells manufactured for a different protocol may be used for LCCC 1606-ATL, if they fit specifications for the protocol and the patient qualifies for the protocol.
Lymphodepletion Regimen
In order to receive lymphodepletion and CAR-T cells, subjects must still have evidence of active disease.
All subjects will receive lymphodepletion with bendamustine 70 mg/m2 and fludarabine 30 mg/m2 for 3 days to reduce possible toxicity associated with the agent prior to administration of CAR-T cells.
NOTE: Any subject who tests positive for Hepatitis B core antibody and negative for Hepatitis B viral load during screening must initiate an anti-Hepatitis B prophylaxis regimen prior to lymphodepletion.
Bendamustine and fludarabine will be administered concomitantly for lymphodepletion (i.e., intravenous (IV) administration of bendamustine 70 mg/m2/day over 3 consecutive days and IV fludarabine 30 mg/m2/day over 3 consecutive days) prior to the first CAR-T cell infusion. Bendamustine should be administered first followed by IV administration of fludarabine.
Cell Administration
ATLCAR.CD30.CCR4 with or without ATLCAR.CD30 cells will be given to eligible subjects 2-14 days (preferably 2-4 days) after lymphodepletion with fludarabine and bendamustine. The dose of cells will vary, depending on the cohort enrolled. The cells will be administered by a licensed provider (oncology nurse or physician) via intravenous injection over 1-10 minutes through either a peripheral or a central line. The expected volume will be 1-50cc. Subjects in the dose expansion part of the study who received the highest safe dose level of ATLCAR.CD30 and ATLCAR.CD30.CCR4 may receive a second infusion of ATLCAR.CD30 and ATLCAR.CD30.CCR4 if cells are available equal to the dose administered for the first cell infusion (or a lower dose).
Duration of Therapy
Therapy in LCCC1606-ATL involves one to two infusion(s) of ATLCAR.CD30.CCR4 with or without ATLCAR.CD30 cells. Treatment with one infusion will be administered unless:
* Subject decides to withdraw from study treatment, OR
* General or specific changes in the subject's condition render the subject unacceptable for further treatment in the judgment of the investigator.
Duration of Follow-up
Subjects who receive a cell infusion will be followed for up to 15 years for replication competent retrovirus (RCR) evaluation or until death, whichever occurs first. Subjects who are removed from study and do not receive the cellular therapy product due to unacceptable adverse events will be followed until resolution or stabilization of the adverse event. Subjects who have progressive disease or initiate another cancer therapy after receiving a cell infusion(s) will still be required to complete abbreviated follow up procedures.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| R01CA247497 | NIH | None | https://reporter.nih.gov/quic… | View |