Autologous B7-H3 Chimeric Antigen Receptor T Cells in Previously Treated Extensive-Stage Small Cell Lung Cancer With Recurrent or Refractory Disease
A Phase I Study to Assess the Safety and Antitumor Activity of Autologous B7-H3 Chimeric Antigen Receptor T Cells in Previously Treated Extensive-Stage Small Cell Lung Cancer With Recurrent or Refractory Disease
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years to 120 Years
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
- Time periods mentioned: 15 years
- Procedures mentioned: Blood draws
Only what the study's summary and detailed description on ClinicalTrials.gov say. Time periods may describe the whole study or a part of it — ask the study team what applies to you.
Show the study's own words
- "They will have blood tests and tests of their heart function."
- "Follow-up visits will continue for 15 years...."
- "Blood and tumor samples will be collected for correlative studies at various timepoints. * After study treatment completion, follow-up will be performed for up to 15 years."
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests B7-H3 CAR T cell therapy, which changes a person's own immune cells to help them attack cancer. It is for adults with small cell lung cancer or a similar cancer outside the lungs that came back or did not respond to treatment. Treatment includes a hospital stay of at least 15 days, with follow-up visits for 15 years.
Background: Small cell lung cancer (SCLC) is the deadliest form of lung cancer. Extrapulmonary neuroendocrine cancer (EPNEC) is a similar type of cancer that develops anywhere other than the lungs. EPNEC is also deadly. B7-H3 is a protein often found in SCLC and EPNEC tumor cells. Researchers can modify a person s own T cells, or immune cells, to target B7-H3. When these modified T cells are returned to the body-a treatment called B7-H3 chimeric antigen receptor (CAR) T cell therapy-they may help kill cancer cells. Objective: To test B7-H3 CAR T cell therapy in people with SCLC or EPNEC. Eligibility: People aged 18 years and older with SCLC or EPNEC that either did not respond or returned after treatment. Design: Participants will be screened. They will have blood tests and tests of their heart function. They will have imaging scans. Participants will undergo apheresis: Blood will be taken from the body through a needle. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different needle. The collected T cells will be altered to make them attack cells with B7-H3. Participants will be in the hospital for at least 15 days. They will receive chemotherapy drugs to prepare their body for the treatment. These drugs will be given through a tube attached to a needle inserted into a vein. The modified T cells will be infused through a vein. Participants will remain in the hospital until they are well enough to go home. Follow-up visits will continue for 15 years....
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Be age 18 or older and have small cell lung cancer or neuroendocrine cancer outside the lungs that came back or did not respond to first treatment.
- Be able to care for yourself and be out of bed or a chair for at least half of your waking hours.
- Have blood oxygen of at least 90% without extra oxygen, and meet the study's heart, liver, kidney, and blood cell test limits.
- Have at least one tumor that can be measured and has not been treated with radiation.
- Recover from most short-term side effects of past cancer treatment and wait the required time after prior treatments before immune cells are collected.
- If you can become pregnant, use highly effective birth control through 12 months after the last chemotherapy dose. If you can father a child, use birth control and do not freeze or donate sperm through 7 months after the last study drug dose.
- If breastfeeding, stop from the start of treatment through 6 months after the last study drug dose.
- Be able to understand the study and agree to sign a consent form.
Who can't join
- A past life-threatening allergic reaction to anti-B7-H3 antibodies, study drugs, or similar treatments.
- A positive HIV or hepatitis C blood test, or active hepatitis B infection.
- Past gene therapy using a tool that inserts genes into cells, except repeat treatment with your own B7-H3 CAR T cells.
- A past blood-forming stem cell transplant from a donor.
- An infection that is not responding to treatment. Infections responding to treatment are allowed.
- A brain or nervous system disorder that could make it hard to check for treatment-related nerve or brain side effects.
- Pregnancy confirmed by a test at screening.
- An uncontrolled illness or other condition that makes the study too risky or makes its results hard to assess.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
* INCLUSION CRITERIA: * Age \>=18 years old. * Histologically confirmed small cell lung cancer (SCLC) or extrapulmonary neuroendocrine cancers (EP-NEC) that has recurred following or is refractory to first-line therapy. Note: small cell cancers of non-lung primary sites are also eligible. * Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2. * Pulse oximetry \>= 90% on room air. * Aspartate Transferase (AST) \< 3 X institutional upper limit of normal (ULN). Note: in case of liver metastases \<= 5 X ULN is acceptable. * Alanine Aminotransferase (ALT) \< 3 X institutional ULN. Note: in case of liver metastases \<= 5 X ULN is acceptable. * Total bilirubin \<=2 X institutional ULN. * Creatinine \<=1.5 X institutional ULN OR creatinine clearance (CrCl) \>= 50 mL/min/1.73m\^2 (calculated by the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] formula or calculated eGFR provided by a laboratory). * Absolute Neutrophil Count (ANC) \>= 750/mcL. * Platelet count \>= 75,000/mcL. * An absolute lymphocyte count (ALC) \>=300/mcL and CD3+ cell count \>=150/mcL. * Normal cardiac ejection fraction as defined by \>= 45% by echocardiogram (ECHO) at screening. * At least 1 measurable lesion by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 that has not been previously irradiated. * Recovered from acute toxic effects of all prior cancer therapy to Grade \<2 per Common Terminology Criteria for Adverse Events (CTCAE) v.6.0 at least one week before apheresis excluding the parameters for ANC and ALC mentioned above. * The following criteria must be met prior to apheresis: * Chemotherapy and biologic/targeted agents: * \>=14 days since the last dose of standard myelosuppressive chemotherapy. * \>= 7 days since the completion of biologic agent, targeted agent, or tyrosine kinase inhibitor therapy. * \>= 3 weeks or 5 half-lives (whichever is shorter) since prior therapy with a monoclonal antibody. * Radiotherapy: * \>= 1 week since the last radiotherapy session. * No washout period required for palliative radiation to non-target lesions. * \>= 3 weeks since hepatic radiation, chemoembolization, and/or radiofrequency ablation. * Steroids and immunosuppressive therapy: * Corticosteroids: \>= 2 weeks since the therapeutic doses (\> 0.5 mg/kg/day prednisone or equivalent). Note: Inhaled or topical steroids are not exclusionary. * Physiologic replacement doses (up to 5 mg/day prednisone equivalent) are allowed and can be adjusted based on participant's BMI if warranted. * \>= 2 weeks since the other immunosuppressive medication (e.g., calcineurin inhibitors, methotrexate, rapamycin, thalidomide, etc.). * Anti-PD-1 and any investigational therapies: * \>= 2 weeks since Anti-PD-1 monoclonal antibody therapy. * \>= 2 weeks or 5 half-lives of the investigational product (whichever is shorter) since any investigational treatment or clinical trial participation. * Other criteria: * 72 hours since small molecule tyrosine kinase inhibitors (e.g., EGFR inhibitors), PARP inhibitors, or KRAS G12C inhibitors. * Individuals of childbearing potential (IOCBP) must agree to use highly effective contraception (hormonal, intrauterine device \[IUD\], abstinence, surgical sterilization) at the study entry and up to 12 months after the last dose of combined chemotherapy. Note: IOCBP is defined as any individual who has experienced menarche and who has not undergone successful surgical sterilization or who is not postmenopausal. * Individuals able to father a child must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 7 months after the last dose of study drugs. We also will recommend individuals able to father a child with partners of childbearing potential ask partners to be on highly effective birth control (hormonal, IUD, surgical sterilization). Individuals able to father a child must not freeze or donate sperm within the same period. * Nursing participants must be willing to discontinue nursing from study treatment initiation through 6 months after the last dose of the study drug(s). * Ability of the participant to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: * History of anaphylactic reactions attributed to anti-B7-H3 antibodies or compounds of similar chemical or biologic composition to autologous B7-H3 CAR T cells, cyclophosphamide, fludarabine, or other agents used in this study. * Infection exposure with the human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C virus (HCV) as defined below: * Positive serology for HIV. * Active HBV infection as demonstrated by test for hepatitis B surface antigen (HBsAg). * Positive serology for HCV. * Prior gene therapy using an integrating vector (except for autologous B7-H3 CAR T cells retreatment). * History of any previous allogeneic hematopoietic stem cell transplant. * Presence of fungal, bacterial, viral, or other infection is permitted if responding to active treatment. * Central Nervous System (CNS) disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement that may impair the ability to evaluate neurotoxicity. * Pregnancy confirmed with beta-human chorionic gonadotropin (beta-HCG) serum or urine pregnancy test in IOCBP at screening. * Uncontrolled intercurrent illness or medical condition(s) evaluated by medical history, physical exam, electrocardiogram (ECG) or situations that would unacceptably increase risk for the participant or impair the ability to evaluate the endpoints of the study.
Study sites (1)
MD
- National Institutes of Health Clinical Center · Bethesda, MD 20892National Cancer Institute Referral Office · Study contact · 888-624-1937 · ncimo_referrals@mail.nih.govMore trials in Bethesda