Peripheral T Cell LymphomaPhase 2NCT04083495
CD30 CAR for Relapsed/Refractory CD30+ T Cell Lymphoma
A Phase 2 study testing ATLCAR.CD30 T cells, Bendamustine and Fludarabine in people with Peripheral T Cell Lymphoma, run by UNC Lineberger Comprehensive Cancer Center at 2 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Peripheral T Cell Lymphoma
- What is being tested?
- ATLCAR.CD30 T cells, Bendamustine and Fludarabine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesUnited States
- Study dates
- 17 Sep 2019to Aug 2038
- Phase
- Phase 2
- 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 18 to 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Written informed consent and HIPAA authorization for release of personal health information explained to, understood by and signed by the subject or legally authorized representative.
- Age ≥ 18 years at the time of consent.
- Karnofsky score of >60%
- Histological or cytological evidence/confirmation of CD30+ peripheral T-cell lymphoma per the 2017 World Health Organization Classification of Haematopoietic and Lymphoid Tissues.
- CD30+ disease determined via archival tissue after the subject's most recent anti-CD30 therapy prior to ATLCAR.CD30 (result can be pending at the time of cell procurement but must be confirmed prior to treatment with the first infusion of ATLCAR.CD30 cells). NOTE: CD30+ disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard.
- Any subjects who has received at least two prior lines of therapy for their lymphoma. If transplant is given as a preplanned consolidation in first remission, it will not be counted as a second line of therapy.
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- Any subject who has received one line of therapy who has primary refractory lymphoma or lymphoma that relapsed within 12 months of completing chemotherapy or receiving transplant as long as prior therapy included brentuximab vedotin unless they were not candidates for brentuximab vedotin.
- Subjects relapsed after autologous stem cell transplant are eligible for this study.
- Subjects relapsed after allogeneic stem cell transplantation are eligible provided the patient is ≥180 days from transplant, not on immunosuppresive therapy to treat/prevent graft-versus-host disease and has no evidence of active graft-versus-host disease.
- Subjects with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
- Female subjects of childbearing potential must have a negative serum pregnancy test within 72 hours prior to cell procurement. Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided.
- Female subjects of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception from the time of informed consent until 6 months after study treatment discontinuation. The two contraception methods can be comprised of two barrier methods, or a barrier method plus a hormonal method or an intrauterine device that meets <1% failure rate for protection from pregnancy in the product label. Women of childbearing potential will also be instructed to tell their male partners to use a condom.
- Subject is willing and able to comply with study procedures based on the judgement of the investigator or protocol designee.
Who cannot join
- Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated on study ).
- Current use of systemic corticosteroids at doses ≥10 mg prednisone daily or its equivalent; those receiving <10 mg daily may be enrolled at discretion of investigator. Inhaled steroids are allowed.
- Active infection with HIV, HTLV, HCV (tests can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells). Note: To meet eligibility subjects are required to be negative for HIV antibody, negative for HTLV1 and 2 antibody or PCR negative for HTLV1 and 2, negative for HCV antibody or HCV viral load.
- Subjects who are positive for hepatitis B surface antigen (can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells) are excluded. Subjects who are hepatitis B surface antigen negative but hepatitis B core antibody positive must have their hepatitis B viral load checked. These subjects will be excluded if their viral load is positive at baseline. Subjects who are core antibody positive and viral load negative at baseline will be considered eligible.
- Eligibility Criteria Prior to Cell Procurement
- Informed consent to undergo cell procurement understood by and signed by the subject or legally authorized representative; subject and/or legally authorized representative given a copy of informed consent form for cell procurement.
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- Subject has life expectancy ≥ 6 weeks.
- Subject has evidence of adequate organ function within 7 days of procurement as defined by:
- Hemoglobin ≥8.0 g/dL (transfusion is allowed prior to procurement)
- Total bilirubin ≤ 2 × ULN, unless attributed to Gilbert's Syndrome
- AST ≤ 3 × ULN
- ALT < 3 x ULN
- Creatinine ≤ 2 × ULN
- Pulse oximetry of >90% on room air
- Imaging results from within 90 days prior to procurement to assess presence of active disease.
- Negative serum pregnancy test within 72 hours prior to procurement or documentation that the subject is post-menopausal. Post-menopausal status must be confirmed with documentation of absence of menses for >1 year, or documentation of surgical menopause (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
- Eligibility Criteria Prior to Lymphodepletion #1
- Written informed consent explained to, understood by and signed by the subject or legally authorized representative; subject and/or legally authorized representative given a copy of informed consent form.
- Imaging results from within 10 days prior to lymphodepletion. Imaging must occur at least 3 weeks after most recent therapy (used as baseline measure for documentation of progression before the lymphodepletion) to document measurable or assessable disease.
- Subject must demonstrate adequate organ function prior to lymphodepletion as defined below. All tests must be obtained within 72 hours prior to lymphodepletion:
- Absolute neutrophil count ≥ 1.0 × 10^9/L
- Platelet count ≥ 50 × 10^9/L
- Total bilirubin < 2 x ULN unless attributed to Gilbert's syndrome
- AST ≤ 5 x ULN
- ALT ≤ 5 x ULN
- Creatinine ≤ 3 x ULN
- Pulse Oximetry of >90% on room air
- Subject must have available autologous transduced activated T cells product at a dose of 2x10^8 cells/m^2 and meets the Certificate of Analysis acceptance criteria.
- No major surgery within 28 days prior to lymphodepletion.
- Negative serum pregnancy test within 72 hours prior to lymphodepleting therapy for female participants of childbearing potential. Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
- Subject has not received any investigational agents or any tumor vaccines within the previous six weeks prior to lymphodepletion.
- Subject has not received anti-CD30 antibody-based therapy within the previous 4 weeks prior to lymphodepletion.
- Subject has not received chemotherapy within the previous 3 weeks prior to lymphodepletion.
- Subject does not have rapidly progressive disease, per treating oncologist's discretion.
- Subject is a good candidate for CAR T cell therapy, per treating oncologist's discretion.
- Subjects on strong inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) as these may increase plasma concentrations of bendamustine, and decrease plasma concentrations of its metabolites. See http://medicine.iupui.edu/clinpharm/ddis/ for an updated list of strong inhibitors of CYP1A2. (This applies to subjects who receive bendamustine for lymphodepletion (required) up through 72 hours after the last dose of bendamustine.)
- Subject is not taking a prohibited or contraindicated medication prior to lymphodepletion.
- Current use of systemic corticosteroids at doses ≥10 mg prednisone daily or its equivalent; those receiving <10 mg daily may be enrolled at discretion of investigator. Inhaled steroids are allowed.
- Eligibility Criteria Prior to Cell Product Administration #1
- Subject has no evidence of uncontrolled infection or sepsis.
- Negative serum pregnancy within 7 days of cell product administration for females of childbearing potential (does not need to be repeated if pre-lymphodepletion pregnancy test is within window). Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oopherectomy) or they are naturally postmenopausal for at least 12 consecutive months.
- Evidence of adequate organ function as defined by:
- Total bilirubin ≤ 2 × ULN, unless attributed to Gilbert's syndrome
- AST ≤ 5 × ULN
- ALT ≤ 5 × ULN
- Creatinine ≤ 3 × ULN
- Pulse Oximetry of >90% on room air
- Subject has no clinical indication of rapidly progressing disease in the opinion of the clinical investigator.
- Subject is a good candidate for treatment with ATLCAR.CD30 cell product per the clinical investigator's discretion.
- Eligibility Criteria Prior to Lymphodepletion #2
- Imaging results from within 21 days prior to lymphodepletion to confirm that the subject has derived clinical benefit from the initial infusion as assessed by the investigator. Clinical benefit will be defined as:
- Subject with stable disease or better after the first ATLCAR.CD30 infusion without subsequent progressive disease.
- Subjects that had a PR or CR and progressed after the first ATLCAR 30 infusion and prior to second lymphodepletion. A second infusion will be made available to the subject, if the subject chooses, if the treating investigator suspects the subject would obtain clinical benefit from a second infusion and all other eligibility criteria are met.
- Subjects who experienced Grade 4 CRS or Grade 4 ICANS as a result of the initial ATLCAR.CD30 infusion are only eligible for a second round of lymphodepletion and infusion if they have partial response or better to the initial ATLCAR.CD30 infusion.
- Subject must demonstrate adequate organ function prior to lymphodepletion as defined below. All tests must be obtained within 24 hours prior to lymphodepletion:
- Absolute neutrophil count ≥ 1.0 × 10^9/L
- Platelet count ≥ 50 × 10^9/L
- Total bilirubin ≤ 2 × ULN, unless attributed to Gilbert's syndrome
- AST ≤ 5 × ULN
- ALT ≤ 5 × ULN
- Creatinine ≤ 3 × ULN
- Pulse Oximetry of >90% on room air
- Subject must have available autologous transduced activated T cells product at a dose of 2x10^8 cells/m^2 and meets the Certificate of Analysis acceptance criteria.
- Negative serum pregnancy test within 72 hours prior to lymphodepleting therapy for female participants of childbearing potential. Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
- Subject does not have evidence of uncontrolled infection or sepsis.
- Subject is not receiving a prohibited medication at time of starting lymphodepletion up through 72 hours after the last dose of cyclophosphamide.
- Subject is a good candidate for CAR T cell therapy, per treating oncologist's discretion.
- Current use of systemic corticosteroids at doses ≥10 mg prednisone daily or its equivalent; those receiving <10 mg daily may be enrolled at discretion of investigator. Inhaled steroids are allowed.
- Eligibility Criteria Prior to Cell Product Administration #2
- Subject has no evidence of uncontrolled infection or sepsis.
- Negative serum pregnancy within 7 days of cell product administration for females of childbearing potential (does not need to be repeated if pre-lymphodepletion pregnancy test is within window). Note: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
- Evidence of adequate organ function as defined by:
- Total bilirubin ≤ 2 × ULN, unless attributed to Gilbert's syndrome
- AST ≤ 5 × ULN
- ALT ≤ 5 × ULN
- Creatinine ≤ 3 × ULN
- Pulse Oximetry of >90% on room air
- Subject has no clinical indication of rapidly progressing disease in the opinion of the clinical investigator.
- Subject is a good candidate for treatment with ATLCAR.CD30 cell product per the clinical investigator's discretion.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
Lineberger Comprehensive Cancer Center at University of North Carolina
Chapel Hill, North Carolina, 27599
Catherine Cheng, 919-445-4208, UNCImmunotherapy@med.unc.edu
Caroline Babinec, 919-962-7426, UNCImmunotherapy@med.unc.edu
- Recruiting
Wake Forest Baptist Medical Center
Winston-Salem, North Carolina, 27157
Jana Hall Project Manager, 919-966-4432, UNCImmunotherapy@med.unc.edu
Caroline Jones Dinkins, 919-966-4432, UNCImmunotherapy@med.unc.edu
About this study
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
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 hope is that 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.
There are risks associated in participating in this research study. Risks of treatment include infection, fever, nausea, vomiting, neurotoxicity, and cytokine release syndrome which can include low blood pressure or difficulty breathing. Other risks are associated with study procedures, such as biopsies, imaging, infusion, and breach of confidentiality.
Read the detailed description
This multicenter, open-label phase II study will determine the efficacy and safety of autologous activated T lymphocytes (ATLs) expressing the chimeric antigen receptor specific for CD30 (ATLCAR.CD30) administered in two sequential infusions in subjects with relapsed/refractory CD30+ PTCL. Up to 20 subjects will receive 2 infusions of 2 × 108 cells/m2 of ATL product expressing the CAR.CD30. It can take time to procure the subjects cells and manufacture the ATLCAR.CD30 cells. During the time period required to manufacture the product the subjects will be able to receive standard of care bridging therapy to be determined by their primary local oncologist. Prior to receiving the first cell infusion, subjects will undergo lymphodepletion with fludarabine and bendamustine. Any subject with prior hypersensitivity reaction to bendamustine will be considered for an alternative lymphodepletion regimen. Subjects will have their disease assessed at week 8 by either CT chest, abdomen and pelvis or PET/CT. Subjects who have stable disease (SD), partial response (PR) or complete response (CR) without subsequent progressive disease and meet the eligibility criteria for a second infusion, will receive lymphodepletion followed by a second infusion. The lymphodepletion for the second infusion will consist of cyclophosphamide and fludarabine.
OUTLINE
Cell Procurement Up to 300 mL of peripheral blood (in up to 3 collections) will be obtained 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.
Bridging Chemotherapy while waiting for CAR_T cells to be prepared Subjects will be allowed to receive additional standard of care therapy (e.g., chemotherapy or radiation therapy) to stabilize their disease if the treating physician feels it is in the subject's best interests.
Lymphodepleting Chemotherapy Prior to the initial cellular product administration subjects will receive a lymphodepleting regimen of bendamustine 70 mg/m^2/day administered IV over 1 hour followed by an IV dose over 30 minutes of fludarabine 30 mg/m^2/day administered over 3 consecutive days. These agents will be administered per institutional guidelines. Prophylaxis (e.g., hydration, antiemetics, etc.) needed prior to fludarabine and bendamustine chemotherapy will be provided per institutional guidelines. Lymphodepletion will be given 2-14 days prior to the initial cell product administration. Subjects who have previously had hypersensitivity to bendamustine may receive a lymphodepletion regimen of cyclophosphamide 300 mg/m^2 IV and fludarabine 30 mg/m^2 each as a daily infusion for 3 days 2-14 days prior to the initial cell product administration.
Two to 14 days prior to the second infusion, subjects will receive a lymphodepletion regimen of cyclophosphamide 300 mg/m^2 IV and fludarabine 30 mg/m^2 each as a daily infusion for 3 days per institutional guidelines. Subjects whose absolute neutrophil count and/or platelet count takes >/= 3 months (from the first day of lymphodepletion prior to the initial cellular product administration) to recover to levels required to meet eligibility for lymphodepletion (ANC >/= 1.0 x 10^9/L and platelet count >/= 50 x 10^9/L) prior to the second infusion will receive a 25% dose reduction in cyclophosphamide and fludarabine lymphodepletion for the second round of lymphodepletion.
ATLCAR.CD30 Cell Administration The cellular product consisting of ATLCAR.CD30 cells will be administered by a licensed healthcare provider (oncology nurse or physician) 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. The expected volume will be 1 - 50 mL. Post lymphodepletion, subjects who meet eligibility criteria for cellular therapy will receive ATLCAR.CD30 cells within 2 - 14 days after completing the lymphodepleting chemotherapy regimen. The recommended phase 2 dose (RP2D) determined in the phase 1 study of ATLCAR.CD30 will be administered to subjects (2 × 108 CAR-T/m2).
If a subject only has enough ATLCAR.CD30 cells product for one infusion, they will still be able to receive one infusion of cells and will not have a 2nd lymphodepletion or infusion of cells. These subjects will be replaced for the purposes of efficacy determination.
Duration of Therapy
Therapy in the study involves 2 infusions of ATLCAR.CD30 cells. Treatment with at least 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 will be followed for up to 15 years from final cell product administration or until death, whichever occurs first.
- Subjects removed from study treatment for unacceptable adverse events will be followed until resolution or stabilization of the adverse event.
- Subjects who experience unequivocal disease progression and start alternate therapy after receiving a cell infusion will still be required to complete abbreviated follow up procedures outlined in the protocol.
- Conditions
- Peripheral T Cell Lymphoma
- Being tested
- ATLCAR.CD30 T cells, Bendamustine, Fludarabine, Cyclophosphamide
- Keywords
- lymphoma, CD30, peripheral T cell lymphoma
- Medical subject headings
- Lymphoma, T-Cell, Peripheral, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATLCAR.CD30 T cellsBiological
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
BendamustineDrug
Also called Bendeka
70 mg/m^2 administered IV for 3 days for lymphodepletion 2-14 days prior to first cell infusion
FludarabineDrug
30 mg/m^2 administered IV for 3 days for lymphodepletion 2-14 days prior to first and second cell infusion
CyclophosphamideDrug
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
| Study group | Role | What they receive |
|---|---|---|
| ATLCAR.CD30 cells | Experimental | 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 Receives: Biological: ATLCAR.CD30 T cells; Drug: Bendamustine; Drug: Fludarabine; Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression free survival (PFS) after administration of the ATLCAR.CD30 in subjects with relapsed/refractory CD30+ peripheral T cell lymphoma
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.
Measured: 8 weeks
Secondary outcomes (6)
Best overall response rate (BOR) mediated by the ATLCAR.CD30 product administered in subjects with relapsed/refractory CD30+ peripheral T cell lymphoma
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.
Measured: 2 years
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.
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.
Measured: 8 weeks
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
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.
Measured: 8 weeks
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
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.
Measured: 8 weeks
Overall survival (OS) after administration of the ATLCAR.CD30 administered to subjects with relapsed/refractory CD30+ peripheral T cell lymphoma
Overall survival is defined from day of initial lymphodepletion for the first administration ATLCAR.CD30 product to date of death.
Measured: 15 years
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
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
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2019
- Study start17 Sep 2019
- Primary completion23 Feb 2028 (estimated)
- Study completionAug 2038 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Peripheral T Cell LymphomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UNC Lineberger Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anne Beaven, MD, Principal investigator, UNC Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04083495
- Sponsor's protocol ID
- LCCC1904-ATL
- Status last verified
- Sep 2026
- First submitted
- 5 Sep 2019
- Last updated
- 24 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04083495
- Acronym / sponsor ID
- LCCC1904-ATL
- Conditions
- Peripheral T Cell Lymphoma
- Keywords
- lymphoma, CD30, peripheral T cell lymphoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- UNC Lineberger Comprehensive Cancer CenterUniversity, hospital or other
- Study start
- 17 Sep 2019 (actual)
- Primary completion
- 23 Feb 2028 (estimated)
- Study completion
- Aug 2038 (estimated)
- First posted
- 10 Sep 2019 (actual)
- 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.
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 hope is that 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.
There are risks associated in participating in this research study. Risks of treatment include infection, fever, nausea, vomiting, neurotoxicity, and cytokine release syndrome which can include low blood pressure or difficulty breathing. Other risks are associated with study procedures, such as biopsies, imaging, infusion, and breach of confidentiality.
Detailed description
This multicenter, open-label phase II study will determine the efficacy and safety of autologous activated T lymphocytes (ATLs) expressing the chimeric antigen receptor specific for CD30 (ATLCAR.CD30) administered in two sequential infusions in subjects with relapsed/refractory CD30+ PTCL. Up to 20 subjects will receive 2 infusions of 2 × 108 cells/m2 of ATL product expressing the CAR.CD30. It can take time to procure the subjects cells and manufacture the ATLCAR.CD30 cells. During the time period required to manufacture the product the subjects will be able to receive standard of care bridging therapy to be determined by their primary local oncologist. Prior to receiving the first cell infusion, subjects will undergo lymphodepletion with fludarabine and bendamustine. Any subject with prior hypersensitivity reaction to bendamustine will be considered for an alternative lymphodepletion regimen. Subjects will have their disease assessed at week 8 by either CT chest, abdomen and pelvis or PET/CT. Subjects who have stable disease (SD), partial response (PR) or complete response (CR) without subsequent progressive disease and meet the eligibility criteria for a second infusion, will receive lymphodepletion followed by a second infusion. The lymphodepletion for the second infusion will consist of cyclophosphamide and fludarabine.
OUTLINE
Cell Procurement Up to 300 mL of peripheral blood (in up to 3 collections) will be obtained 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.
Bridging Chemotherapy while waiting for CAR_T cells to be prepared Subjects will be allowed to receive additional standard of care therapy (e.g., chemotherapy or radiation therapy) to stabilize their disease if the treating physician feels it is in the subject's best interests.
Lymphodepleting Chemotherapy Prior to the initial cellular product administration subjects will receive a lymphodepleting regimen of bendamustine 70 mg/m^2/day administered IV over 1 hour followed by an IV dose over 30 minutes of fludarabine 30 mg/m^2/day administered over 3 consecutive days. These agents will be administered per institutional guidelines. Prophylaxis (e.g., hydration, antiemetics, etc.) needed prior to fludarabine and bendamustine chemotherapy will be provided per institutional guidelines. Lymphodepletion will be given 2-14 days prior to the initial cell product administration. Subjects who have previously had hypersensitivity to bendamustine may receive a lymphodepletion regimen of cyclophosphamide 300 mg/m^2 IV and fludarabine 30 mg/m^2 each as a daily infusion for 3 days 2-14 days prior to the initial cell product administration.
Two to 14 days prior to the second infusion, subjects will receive a lymphodepletion regimen of cyclophosphamide 300 mg/m^2 IV and fludarabine 30 mg/m^2 each as a daily infusion for 3 days per institutional guidelines. Subjects whose absolute neutrophil count and/or platelet count takes >/= 3 months (from the first day of lymphodepletion prior to the initial cellular product administration) to recover to levels required to meet eligibility for lymphodepletion (ANC >/= 1.0 x 10^9/L and platelet count >/= 50 x 10^9/L) prior to the second infusion will receive a 25% dose reduction in cyclophosphamide and fludarabine lymphodepletion for the second round of lymphodepletion.
ATLCAR.CD30 Cell Administration The cellular product consisting of ATLCAR.CD30 cells will be administered by a licensed healthcare provider (oncology nurse or physician) 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. The expected volume will be 1 - 50 mL. Post lymphodepletion, subjects who meet eligibility criteria for cellular therapy will receive ATLCAR.CD30 cells within 2 - 14 days after completing the lymphodepleting chemotherapy regimen. The recommended phase 2 dose (RP2D) determined in the phase 1 study of ATLCAR.CD30 will be administered to subjects (2 × 108 CAR-T/m2).
If a subject only has enough ATLCAR.CD30 cells product for one infusion, they will still be able to receive one infusion of cells and will not have a 2nd lymphodepletion or infusion of cells. These subjects will be replaced for the purposes of efficacy determination.
Duration of Therapy
Therapy in the study involves 2 infusions of ATLCAR.CD30 cells. Treatment with at least 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 will be followed for up to 15 years from final cell product administration or until death, whichever occurs first.
- Subjects removed from study treatment for unacceptable adverse events will be followed until resolution or stabilization of the adverse event.
- Subjects who experience unequivocal disease progression and start alternate therapy after receiving a cell infusion will still be required to complete abbreviated follow up procedures outlined in the protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| ATLCAR.CD30 cells | Experimental | Biological: ATLCAR.CD30 T cells, Drug: Bendamustine, Drug: Fludarabine, Drug: CyclophosphamideThe 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 |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Written informed consent and HIPAA authorization for release of personal health information explained to, understood by and signed by the subject or legally authorized representative.
- Age ≥ 18 years at the time of consent.
- Karnofsky score of >60%
- Histological or cytological evidence/confirmation of CD30+ peripheral T-cell lymphoma per the 2017 World Health Organization Classification of Haematopoietic and Lymphoid Tissues.
- CD30+ disease determined via archival tissue after the subject's most recent anti-CD30 therapy prior to ATLCAR.CD30 (result can be pending at the time of cell procurement but must be confirmed prior to treatment with the first infusion of ATLCAR.CD30 cells). NOTE: CD30+ disease requires documented CD30 expression by immunohistochemistry based on the institutional hematopathology standard.
Key exclusion criteria (79 listed)
- Subject is pregnant or lactating (Note: Breast milk cannot be stored for future use while the mother is being treated on study ).
- Current use of systemic corticosteroids at doses ≥10 mg prednisone daily or its equivalent; those receiving <10 mg daily may be enrolled at discretion of investigator. Inhaled steroids are allowed.
- Active infection with HIV, HTLV, HCV (tests can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells). Note: To meet eligibility subjects are required to be negative for HIV antibody, negative for HTLV1 and 2 antibody or PCR negative for HTLV1 and 2, negative for HCV antibody or HCV viral load.
- Subjects who are positive for hepatitis B surface antigen (can be pending at the time of cell procurement; only those samples confirming lack of active infection will be used to generate transduced cells) are excluded. Subjects who are hepatitis B surface antigen negative but hepatitis B core antibody positive must have their hepatitis B viral load checked. These subjects will be excluded if their viral load is positive at baseline. Subjects who are core antibody positive and viral load negative at baseline will be considered eligible.
- Eligibility Criteria Prior to Cell Procurement
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 |
|---|---|---|
| ATLCAR.CD30 T cellsAutologous 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 | Biological | ATLCAR.CD30 cells |
| BendamustineAlso: Bendeka70 mg/m^2 administered IV for 3 days for lymphodepletion 2-14 days prior to first cell infusion | Drug | ATLCAR.CD30 cells |
| Fludarabine30 mg/m^2 administered IV for 3 days for lymphodepletion 2-14 days prior to first and second cell infusion | Drug | ATLCAR.CD30 cells |
| Cyclophosphamide300 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 | Drug | ATLCAR.CD30 cells |
Primary outcome
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.
6 secondary outcomes
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
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
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
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
Overall survival (OS) after administration of the ATLCAR.CD30 administered to subjects with relapsed/refractory CD30+ peripheral T cell lymphoma
Time frame: 15 years
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
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 24 Sep 2026.
- UNC Lineberger Comprehensive Cancer CenterLink provided by the sponsor.
- 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.
Anne Beaven, MD principal investigator
UNC Chapel Hill
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ATLCAR.CD30 T cells, Bendamustine and Fludarabine in people with Peripheral T Cell Lymphoma, run by UNC Lineberger Comprehensive Cancer Center 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 79 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: looking for participants now, as of the sponsor's last update on 24 Sep 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Contact Lori Stravers (919-966-4432, UNCImmunotherapy@med.unc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression free survival (PFS) after administration of the ATLCAR.CD30 in subjects with relapsed/refractory CD30+ peripheral T cell lymphoma (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 24 Sep 2026; AzTrials last refreshed its copy on 31 Oct 2026.