ClinicalTrials.gov record NCT05281809
Local Manufacture of CAR T-Cell Products for the Treatment of B-Cell Lymphoma and B-Acute Lymphoblastic Leukemia
A Feasibility Study Following a Phase 2a Design to Demonstrate Successful Local Manufacture of Chimeric Antigen Receptor (CAR) T-Cell Products for the Treatment of B-Cell Lymphoma and B-Acute Lymphoblastic Leukemia
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
This Phase 2 interventional study tests whether a site can consistently make CD19-directed CAR T-cells using an automated device and safely give them to people with CD19+ B-cell lymphomas or B‑ALL. Participants have their T-cells collected (apheresis), receive lymphodepleting chemotherapy, then an infusion of their own locally manufactured CAR T-cells, followed by monitoring for side effects and response. The study includes short-term safety monitoring and long-term follow-up and reporting.
What it is studying. The study is trying to show two things: that CD19-directed CAR T-cells can be produced reliably at the local site using the CliniMACS Prodigy system and a lentiviral CAR19 vector, and that giving those locally manufactured autologous CAR T-cells can be done with acceptable safety as measured by adverse events including cytokine release syndrome (CRS) and neurotoxicity (ICANS). It also collects data on patient responses and CAR T-cell levels after infusion.
What the researchers hope to learn. Scientific goals are to demonstrate feasibility of reliable local manufacture of CD19 CAR T-cells, to document the safety profile of administering the locally produced product (including rates and severity of CRS and ICANS), to record response rates using standard response criteria, and to measure CAR T-cell kinetics after infusion.
What this study is about
The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.
This trial aims to demonstrate the feasibility of this approach to reliably generate product and to safely administer the product to patients who have B-Cell Lymphoma and B-Acute Lymphoblastic Leukemia.
Interventions being studied
Being studied in this trial does not mean the treatment or procedure is approved or available for this condition.
- Drug
- Chimeric Antigen Receptor (CAR) T-Cell Product (Autologous)
Eligibility
The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.
Inclusion criteria
- Subjects with CD19+ B-cell lymphoma or B-Cell Acute Lymphoblastic Leukemia (B-ALL) with no currently available curative treatment option (such as autologous or allogeneic Hematopoietic stem cell transplantation (HSCT)) who have a limited prognosis (<2-year projected survival) will be enrolled. Participation on this trial is permitted as a bridge to HSCT.
- Peripheral blood CD3 count > 200/µL by flow cytometry. Please note that this test might need to be repeated multiple times as standard practice to optimize collection efficiency.
- Subjects will have a diagnosis of Diffuse Large B Cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Mantle Cell Lymphoma (MCL), CLL, Marginal Zone Lymphoma (MZL), Lymphoplasmacytic Lymphoma (LPL) or B-ALL and will have failed at least 2 lines of therapy in the case of lymphoma and one line if the diagnosis is B-ALL or be refractory (no response or progressive disease) to first line therapy. A line of therapy must include conventional (immuno) chemotherapy (e.g. rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHOP) or Bendamustine plus Rituximab (BR) in the case of lymphoma) administered for at least 2 cycles. Second or greater lines of therapy must be administered for at least two cycles. Single agent anti-CD20 monoclonal antibody (e.g. rituximab, obinutuzumab) is not considered for the purposes of these criteria to count as a line of therapy. The definition of a line of therapy is taken according to recommended regimens for first and second line therapy in the relevant sections of the National Comprehensive Cancer Network (NCCN) guidelines. The most recent version of the guidelines will be used for eligibility determination. In the unlikely event that a subject received a first or second line regimen no longer listed in the most recent guidelines, but previously present in the version of the guidelines active at the time the therapy was administered, then the subject would be deemed to have received a line of therapy.
- Subjects with pathological and clinical evidence of transformed indolent lymphoma (FL, CLL, MZL or LPL) are eligible for participation on this trial if they have received at least one line of therapy for transformed disease for at least two cycles regardless of response.
- Demonstration of CD19 expression by immunohistochemistry or flow cytometry on a pathological specimen of lymphoma or ALL cells at any time in the course of prior treatment.
- Subjects who are unable to receive commercially available CD19-CAR T-cell therapy.
- Patients with lymphoma must have measurable or assessable disease. Patients in complete remission with no evidence of disease are not eligible.
- Patients with B-ALL must have at least measurable detectable disease on two separate occasions at least 2 weeks apart to be eligible.
- Subjects who relapse at > 100 days after autologous or allogeneic HSCT are eligible for participation on this trial. Allogeneic HSCT recipients must be off all immunosuppression for a minimum of 4 weeks before leukapheresis is performed and be free of active acute and chronic Graft Versus Host Disease (GVHD).
- Subjects will be ≥ 18 and < 80 years of age.
- Female subjects of childbearing potential must have a negative urine or serum pregnancy test and if sexually active must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive. Active contraception should continue for at least one year after CAR T-cell infusion.
- Male participants must be willing to practice birth control from the time of enrollment on this study and for 6 months after receiving the preparative regimen.
- Cardiac ejection fraction ≥ 0.45 by MUGA (multigated acquisition) or echocardiography.
- No requirement for supplemental oxygen and no dyspnea at rest. DLCO (diffusing capacity of the lungs for carbon monoxide) and FEV (forced expiratory volume)1 ≥ 0.65 of predicted.
- Karnofsky performance score ≥ 70.
- Subjects must have an expected survival > 12 weeks.
- Subjects must be able to comprehend the risks and methods used in this clinical trial and independently consent to participate.
- Subjects must consent to anonymous reporting of data to the CIBMTR (Center for International Blood and Marrow Transplant Research).
Exclusion criteria
- Infection with HIV (human immunodeficiency virus) and active viral replication. Patients with an undetectable viral load on ART (antiretroviral treatment) can be considered for participation on this protocol.
- Infection with hepatitis B and active viral replication.
- Infection with hepatitis C and active viral replication.
- Active untreated CNS (central nervous system) leukemia or lymphoma. Patients with treated CNS leptomeningeal or parenchymal disease might be eligible if the CNS disease is inactive. The CSF (cerebrospinal fluid) must be clear on two separate occasions at least 4 weeks apart. Brain imaging must demonstrate no evidence of progressive disease on two separate occasions at least 4 weeks apart.
- Active bacterial, fungal or viral infection.
- Concurrent second malignancy requiring active therapy. Patients with breast or prostate cancer stable on hormonal therapy might be considered for participation if otherwise unimpaired.
- Documented myocardial infarction within 6 months of study participation and/or symptomatic coronary artery or valvular disease or uncontrolled arrhythmia.
- Investigational drug use within 30 days before leukapheresis.
- Anti-cancer therapy administration within 4 weeks of leukapheresis including antiCD19 directed therapy, monoclonal antibody therapy, bi-specific T-cell engager therapy and targeted therapy such as Abelson tyrosine kinase inhibitors, Bruton's tyrosine kinase inhibitors, venetoclax and Lenalidomide or other IMiD (Immunomodulatory Drug).
- Involved field radiation therapy is permitted if it terminates at least 15 days before leukapheresis and associated toxicity is grade 2 or less. Radiation therapy within 14 days of leukapheresis would make the subject ineligible.
- Checkpoint inhibitor therapy within 4 weeks before leukapheresis.
- Corticosteroid therapy at pharmacological dose (> 10 mg of prednisone or biological equivalent) within 4 weeks before leukapheresis.
- Immunosuppressive therapy that cannot be stopped for 4 weeks prior to leukapheresis as deemed by the prescribing physician.
- Laboratory abnormalities that indicate clinically significant hematological, hepatobiliary, or renal disease:
- AST (Aspartate transaminase)/SGOT(serum glutamic-oxaloacetic transaminase) > 2.0 times the upper limit of normal ALT (alanine aminotransferase)/SGPT (serum glutamic-pyruvic transaminase) > 2.0 times the upper limit of normal Total bilirubin > 2.0 times the upper limit of normal, unless subject has Gilbert's Syndrome (>3.0 times the upper limit of normal) Hemoglobin < 8 gm/dL or dependent upon transfusion to maintain ≥ 8 gm/dL White blood cell count < 2,000/mm3 Platelet count < 50,000/mm3 or dependent upon transfusion to maintain ≥ 50,000 mm Creatinine > 2.0 times the upper limit of normal or calculated creatinine clearance ≤ 40 mL/min.
- Pregnant or lactating females.
- Subjects who, in the opinion of the Investigator, will be non-compliant with study schedules or procedures.
- Subjects who belong to a vulnerable population such as the homeless, the developmentally disabled and prisoners or have any condition that impairs their ability to provide informed consent or comply with study schedules or procedures.
Study description and what participation involves
The study's detailed description, as published on ClinicalTrials.gov.
Show the detailed description from the registry
On this study the following procedures are sequentially performed: eligibility determination and informed consent; cell collection by apheresis; CAR T-cell manufacturing and lymphodepleting chemotherapy all followed by CAR T-cell infusion on day 0. The first 3 subjects will be followed in hospital from day 0 until +14 for CRS, ICANS and other toxicity. The PI and two physicians not affiliated with the study (Nathan Bahary, MD, PhD and Gene Finley, MD) will review the outcome of the first three patients to assure the interim analysis meets criteria for continuing accrual. This analysis will be submitted to the IRB prior to continuing with accrual. The toxicity profile of the first three subjects will be scrutinized. Should toxicity be minimal with CRS ≤ 2 and ICANS grade ≤1 then the PI might propose modification to hospitalization between days 0 and +14 according to comparison with prior experience with commercially available product. A protocol amendment would be submitted in this case. Should no CAR T-cell related toxicity be identified on day +15, the subject will be discharged from the hospital and followed in the Medical Short Stay Unit (or designated substitute inpatient unit) daily to day 30. At the discretion of the Investigator (based upon each subject's medical condition or status), this follow-up could be reduced to thrice weekly basis (e.g. Monday-Wednesday-Friday). CAR T-cell monitoring by flow cytometry will occur on day +30 and day +100. Response will be assessed at day +30 and the subject will be discharged for outpatient follow up. Response will be assessed monthly by clinical examination to day +100 and then every 3 months to day +730. Thereafter, clinical follow up will occur every 6 months to five years and then yearly up to 15 years, or until death (whichever occurs first). All subjects treated on this study must consent to reporting of de-identified data to the Center for International Blood and Marrow Transplantation Research (CIBMTR). (See Table 1: Schedule of Study Procedures, Figure 1: Study Diagram, Table 2: Laboratory Investigation and Table 3: Response Evaluation for details of study conduct.) The clinical care of subjects enrolled on this study is entirely within the standard of care employed for patients who receive commercial product. There are no drugs, surgical procedures, radiological investigations, laboratory tests or examinations that are considered experimental except for a peripheral blood sample to detect CAR T-cells (by flow cytometry) and the actual production/manufacture of CAR T-cells occurring in the local Cell Processing Laboratory. For this reason, the intent of this protocol is to ensure that the standard of care is strictly followed as outlined in the SOP documents, screenshots and documents included in the appendix of this document. Thus, patients receiving commercial product and those treated on this protocol should receive the same supportive care. In addition to immune effector cells, these documents often describe methods and cellular therapy products not relevant to this investigation and for our purpose these sections can be ignored.
AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴
AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.
If enrolled you would give informed consent, have T cells collected by leukapheresis, and those cells would be manufactured locally into CD19 CAR T‑cells. You would receive lymphodepleting chemotherapy, then an intravenous CAR T‑cell infusion (day 0) and intensive monitoring for cytokine release syndrome and neurologic toxicity—including possible hospitalization around the infusion. Blood tests (including samples to detect CAR T‑cells by flow cytometry) will be done at set times (for example day +30 and +100) and disease response is assessed at day +30 with regular follow‑up visits for months and years afterward. You must agree to de‑identified data reporting to the Center for International Blood and Marrow Transplantation Research (CIBMTR).
How the study is structured. This is an open-label, single-group Phase 2 treatment study. Each participant undergoes leukapheresis to collect T-cells, local CAR T-cell manufacture, lymphodepleting chemotherapy, and a single CAR T-cell infusion. Early participants will have closer inpatient monitoring for CRS and ICANS; all participants have scheduled clinical assessments, CAR T-cell testing by flow cytometry (including day +30 and +100), and long-term follow-up with data reported to a transplant registry.
Questions you could ask
These questions are suggestions for a conversation with the study team or your own clinician, not advice.
- The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
- Which of the eligibility criteria would need to be checked with tests before I could join?
More on Waldenström macroglobulinemia
Important dates
- Study start
- Apr 19, 2022
- Primary completion
- Aug 5, 2037 (estimated)
- Study completion
- Dec 1, 2037 (estimated)
- Target enrollment
- 30 participants (estimated)
- Last updated on registry
- Jan 13, 2025
- Data verified
- Oct 10, 2026
Sponsor and research team
The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.
- Lead sponsor
- John Lister
- Collaborators
- Lentigen Technology, Inc.
- Miltenyi Biotec, Inc.
- Allegheny Health Network
Central study contact
If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.
- John Lister, MD 📞 412-578-4484 ✉ john.lister@ahn.org
Participating sites (1)
- AHN Cancer Institute - West Penn HospitalRecruiting
Pittsburgh, Pennsylvania, 15224 · United States
- John Lister, MD · 4125784484 · john.lister@ahn.org
- AHN Clinical Trials Contact · 412-330-6011 · clinicaltrials@ahn.com
- Cyrus Khan, MD
- Salman Fazal, MD
- Anna Koget, DO
- Prerna Mewawalla, MD
- Santhosh Sadashiv, MD
- Yazan Samhouri, MD
- Thomas Curley, MD
Terms used on this page · explanations by MedicalUpdates.ai
- HSCT
- A procedure that replaces blood-forming cells after high-dose treatment. 'Autologous' uses the person's own cells collected beforehand; 'allogeneic' uses cells from a donor.
- lines of therapy
- Treatment a person has already had for the condition. A 'line of therapy' is one course of treatment; studies often require, or limit, the number of prior lines.
- refractory
- A condition that has not responded to a treatment. 'Relapsed' means it responded and then came back; 'refractory' means it did not respond in the first place.
- prednisone
- Steroid medicines, such as prednisone, that reduce inflammation. Studies often require a stable dose at entry or measure whether the study treatment allows the dose to be reduced.
- CAR T
- A treatment in which a person's own immune cells (T cells) are collected, modified in a laboratory to recognise a target, and returned to the body.
- complete remission
- No sign of the condition can be found with the tests used in the study. It does not always mean the condition is gone permanently, and the definition depends on the condition and the study.
- relapse
- A condition that improved with treatment and has since returned or worsened.
- childbearing potential
- Studies often ask participants who could become pregnant, or could father a child, to use contraception during the study and for a period afterwards, because the effect of the treatment on a pregnancy is unknown.
- enrollment
- The number of participants a study plans to include, or has included. 'Estimated' means the planned number; 'actual' means the number who joined.
- echocardiography
- An ultrasound scan of the heart. A transesophageal echocardiogram is done through a probe passed into the food pipe for a closer view.
- DLCO
- A breathing test that measures how well the lungs pass oxygen from the air into the blood.
- Karnofsky
- A scale from 100 (no complaints) down to 0 that describes how well a person can carry out daily activities. Studies often require a minimum score.
- Investigational drug
- A treatment that is being tested and has not been approved for this use. It may be approved for a different condition. Being studied does not mean it works or is available outside the study.
- T-cell engager
- An engineered antibody that attaches to two targets at once, often linking an immune cell to a diseased cell so the immune cell can attack it.
- Immunosuppressive
- A medicine that reduces the activity of the immune system. Studies of autoimmune conditions often require a stable dose, a prior failure, or a washout of such medicines.
- upper limit of normal
- The highest value of a blood test that a laboratory considers normal. Criteria such as '≤ 3 × ULN' mean the result must be no more than three times that value.
- creatinine clearance
- A measure of kidney function, calculated from a blood creatinine level together with age, weight and sex.
- informed consent
- The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
- Inclusion Criteria
- The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
- Exclusion Criteria
- The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.
- CRS
- A reaction in which the immune system releases a large amount of signalling proteins at once, causing fever and sometimes low blood pressure or breathing problems. It can occur after some immune therapies, such as CAR-T cells or bispecific antibodies.
- ICANS
- Nervous-system side effects, such as confusion or difficulty speaking, that can occur after some immune therapies. Usually temporary, but monitored closely.
- follow-up
- The period after treatment or enrolment during which participants are observed or contacted, for example to record side effects or outcomes.
- standard of care
- Treatment generally considered appropriate for a condition in a particular clinical setting. It can vary by patient, place and over time. In many studies the new treatment is added to, or compared with, standard of care.
The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.
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