CD30 CAR for Relapsed/Refractory CD30+ T Cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT04083495|
Recruitment Status : Recruiting
First Posted : September 10, 2019
Last Update Posted : August 24, 2021
This is a research study to determine the safety and tolerability of ATLCAR.CD30 for treating relapsed/refractory Peripheral T Cell Lymphoma. Blood samples will be collected from study participants and the immune T cells will be separated. T cells will be genetically modified in a laboratory at UNC-Chapel Hill to enable them to produce CD30 antibody. The modified T cells, called ATLCAR.CD30, will be able to target and attach to lymphoma cancer cells that carry the CD30 antigen. Once they are attached, the T cells will attack and destroy the lymphoma cancer cells. To prepare the body for the ATLCAR.CD30 cells, participants will complete lymphodepletion with two chemotherapy agents. Lymphodepletion will happen over three days prior to ATLCAR.CD30 infusion. If participants respond to this treatment, and there are sufficient unused ATLCAR.CD 30 cells, they may be eligible to receive a second infusion. The second infusion will be given after a second lymphodepletion chemotherapy. Most of the clinic visits in this research will last between 1-8 hours.
Participants will be followed closely for 4 consecutive weeks after ATLCAR.CD30 infusion(s). Other follow-up visits will happen on Weeks 6 and 8, and continue every 3 months for the first year after infusion. Long-term follow up will continue annually for up to 15 years after the last ATLCAR.CD30 infusion.
There are risks associated in participating in this research study. Risks of treatment include pain, fever, nausea, vomiting, and neurotoxicity. Other risks are associated with study procedures, such as biopsies, imaging, infusion, and breach of confidentiality.
|Condition or disease||Intervention/treatment||Phase|
|Peripheral T Cell Lymphoma||Biological: ATLCAR.CD30 T cells Drug: Bendamustine Drug: Fludarabine Drug: Cyclophosphamide||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Study of the Administration of T Lymphocytes Expressing the CD30 Chimeric Antigen Receptor (CAR) for Relapsed/Refractory CD30+ Peripheral T Cell Lymphoma|
|Actual Study Start Date :||September 17, 2019|
|Estimated Primary Completion Date :||August 2022|
|Estimated Study Completion Date :||August 2037|
Experimental: ATLCAR.CD30 cells
The cellular product consisting of ATLCAR.CD30 cells will be administered via intravenous injection over 5 - 10 minutes through either a peripheral or a central line. The volume of infusion will depend upon the concentration of the cells when frozen and the size of the subject. Administration to eligible subjects will occur within 2 - 14 days after completing the lymphodepleting chemotherapy regimen
Biological: ATLCAR.CD30 T cells
Autologous T Lymphocyte Chimeric Antigen Receptor cells targeted against the CD30 antigen at dose of 2 × 10^8 CAR-T/m^2 with a maximum dose of 5 × 10^8 CAR-T cells
70 mg/m^2 administered IV for 3 days for lymphodepletion 2-14 days prior to first cell infusion
Other Name: Bendeka
30 mg/m^2 administered IV for 3 days for lymphodepletion 2-14 days prior to first and second cell infusion
300 mg/m^2 administered IV for 3 days for lymphodepletion 2-14 days prior to second cell infusion and 2-14 days prior to the first cell infusion for subjects who have previously had hypersensitivity to bendamustine
- Progression free survival (PFS) after administration of the ATLCAR.CD30 in subjects with relapsed/refractory CD30+ peripheral T cell lymphoma [ Time Frame: 8 weeks ]PFS is defined from day of initial lymphodepletion administration of the first ATLCAR.CD30 product infusion to the date of disease progression per the Revised Lugano Criteria or death as a result of any cause. Subjects who do not meet criteria for progression by the analysis data cut-off date will be censored at their last evaluable disease assessment date.
- Best overall response rate (BOR) mediated by the ATLCAR.CD30 product administered in subjects with relapsed/refractory CD30+ peripheral T cell lymphoma [ Time Frame: 2 years ]The best overall response rate (BOR) will be defined as the best response recorded from the first administration of the ATLCAR.CD30 product to the date of disease progression per the Revised Lugano Criteria or death as a result of any cause.
- Objective response rate (ORR) mediated by the first infusion of the ATLCAR.CD30 product administered in patients with relapsed/refractory CD30+ peripheral T cell lymphoma. [ Time Frame: 8 weeks ]The objective response rate (ORR) will be defined as the rate of complete responses (CR) + partial responses (PR) by 8 weeks from the date of first lymphodepletion prior to the first administration of the ATLCAR.CD30 product per the Revised Lugano Criteria.
- Responses improved by the second infusion of the ATLCAR.CD30 product administered in subjects with either partial response or stable disease following the first infusion of ATLCAR.CD30 [ Time Frame: 8 weeks ]The percentage of subjects who have an improvement in their response after the second administration of ATLCAR.CD30 product will be defined at 8 weeks after the second administration of the ATLCAR.CD30 product per the Revised Lugano Criteria. Subjects entering the second infusion in a complete response will be reported as continued CR (CCR) but will not be included in percentage of improved responses after the second infusion.
- Incidence of Dose Limiting Toxicity (DLT) (safety and tolerability) when administering two sequential infusions of the ATLCAR.CD30 product in subjects with relapsed/refractory CD30+ peripheral T cell lymphoma [ Time Frame: 8 weeks ]DLT defined as ≥ Grade 3 cytokine release syndrome (CRS), Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), or any other ≥ Grade 3 non-hematologic toxicity, including allergic reactions to T cell infusions. Toxicity will be classified and graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE), version 5.0. CRS toxicity will be graded according to CRS Grading Criteria and Management Guidelines Version 3.0 (March 14, 2019). ICANS toxicity will be graded according to the ICANS Grading Criteria for Management of Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) for CAR T-Cell Therapy.
- Overall survival (OS) after administration of the ATLCAR.CD30 administered to subjects with relapsed/refractory CD30+ peripheral T cell lymphoma [ Time Frame: 15 years ]Overall survival is defined from day of initial lymphodepletion for the first administration ATLCAR.CD30 product to date of death.
- Comparison of the expansion and persistence of ATLCAR.CD30 in peripheral blood when infused after a single infusion of ATLCAR.CD30 cells and after two infusions with ATLCAR.CD30 cells [ Time Frame: 1 year ]Persistence and expansion of ATLCAR.CD30 in peripheral blood after a single infusion and after two infusions will be determined by quantitative polymerase chain reaction (PCR) and flow cytometry in sample of peripheral blood. Feasibility is defined as ability of subjects to receive 2 sequential infusions taking into account manufacturing and any other limiting factors to receiving a second infusion of ATLCAR.CD30
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04083495
|Contact: Catherine Chengfirstname.lastname@example.org|
|Contact: Spencer Laingemail@example.com|
|United States, North Carolina|
|Lineberger Comprehensive Cancer Center at University of North Carolina||Recruiting|
|Chapel Hill, North Carolina, United States, 27599|
|Contact: Catherine Cheng 919-445-4208 firstname.lastname@example.org|
|Contact: Spencer Laing 919-962-8618 email@example.com|
|Sub-Investigator: Natalie Grover, MD|
|Sub-Investigator: Paul Armistead, MD|
|Sub-Investigator: Jonathan Serody, MD|
|Sub-Investigator: Maurice Alexander, PharmD|
|Sub-Investigator: Tatjana Grgic, PharmD|
|Sub-Investigator: Jonathan Ptachcinski, PharmD|
|Sub-Investigator: James Shaw, PharmD|
|Sub-Investigator: Edith Bowers|
|Sub-Investigator: Faith Buchanan|
|Sub-Investigator: James Coghill|
|Sub-Investigator: Catherine Coombs|
|Sub-Investigator: Christopher Dittus, MD|
|Sub-Investigator: Katarzyna Jamieson|
|Sub-Investigator: Emily Kassam|
|Sub-Investigator: Winnie Lau|
|Sub-Investigator: Yara Park|
|Sub-Investigator: Alicia Pinto|
|Sub-Investigator: Raghuveer Ranganathan|
|Sub-Investigator: Marcie Riches, MD|
|Sub-Investigator: Angela Spruill|
|Sub-Investigator: Megan Sterlina|
|Sub-Investigator: Hendrik VanDeventer, MD|
|Sub-Investigator: Benjamin Vincent|
|Sub-Investigator: Timothy Voorhees, MD|
|Sub-Investigator: Kimberly Wehner|
|Sub-Investigator: Michael Winstead|
|Sub-Investigator: William Wood|
|Sub-Investigator: Ashley Zanter|
|Sub-Investigator: Megan McElfresh|
|Wake Forest Baptist Medical Center||Recruiting|
|Winston-Salem, North Carolina, United States, 27157|
|Contact: Jana Hall Project Manager 919-966-4432 firstname.lastname@example.org|
|Contact: Caroline Jones Dinkins 919-966-4432 email@example.com|
|Principal Investigator: Rakhee Vaidya, MD|
|Principal Investigator:||Anne Beaven, MD||UNC Chapel Hill|