Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing t… (NCT03745326) | Clinical Trial Compass
TerminatedPhase 1/2
Administering Peripheral Blood Lymphocytes Transduced With a Murine T-Cell Receptor Recognizing the G12D Variant of Mutated RAS in HLA-A*11:01 Patients
Stopped: Study was closed due to lack of accrual and study outcomes overlapped with another protocol's eligibility.
United States5 participantsStarted 2019-05-16
Plain-language summary
Background:
A new cancer therapy takes white blood cells from a person, grows them in a lab, genetically changes them, then gives them back to the person. Researchers think this may help attack tumors in people with certain cancers. It is called gene transfer using anti-Kirsten rat sarcoma virus (KRAS) Glycine(G) to Aspartic Acid(D) substitution at codon 12(G12D) murine T-cell receptor (mTCR) cells.
Objective:
To see if anti-KRAS G12D mTCR cells are safe and cause tumors to shrink.
Eligibility:
Adults ages 18-72 who have cancer with a molecule on the tumors that can be recognized by the study cells
Design:
Participants will be screened with medical history, physical exam, scans, photography, and heart, lung, and lab tests.
An intravenous (IV) catheter will be placed in a large vein in the chest.
Participants will have leukapheresis. Blood will be removed through a needle in an arm. A machine will divide the blood and collect white blood cells. The rest of the blood will be returned to the participant through a needle in the other arm.
A few weeks later, participants will have a hospital stay. They will:
* Get 2 chemotherapy medicines by IV over 5 days.
* Get the changed cells through the catheter. Get up to 9 doses of medicine to help the cells. They may get a shot to stimulate blood cells.
* Recover in the hospital for up to 3 weeks. They will provide blood samples.
Participants will take an antibiotic for at least 6 months.
Participants will have several follow-up visits over 2 years. They will repeat most of the screening tests and may have leukapheresis.
Participants blood will be collected for several years.
Who can participate
Age range
18 Years – 72 Years
Sex
ALL
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AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Measurable (per Response Evaluation Criteria in Solid Tumors v1.1 criteria), metastatic, or unresectable malignancy expressing G12D mutated KRAS as assessed by one of the following methods: Reverse Transcription Polymerase Chain Reaction (RT-PCR) on tumor tissue, tumor deoxyribonucleic acid (DNA) sequencing, or any other Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory test on resected tissue. Patients shown to have tumors expressing Glycine(G) to Aspartic Acid(D) substitution at codon 12(G12D) mutated neuroblastoma rat sarcoma (NRAS) and Harvey rat sarcoma viral oncogene homolog (HRAS) will also be eligible as these oncogenes share complete amino acid homology with G12D mutated KRAS for their first 80 N-terminal amino acids, completely encompassing the target epitope.
. Patients must be human leukocyte antigens (HLA) -A\*11:01 positive as confirmed by the National Institutes of Health (NIH) Department of Transfusion Medicine.
. Confirmation of the diagnosis of cancer by the National Cancer Institute (NCI) Laboratory of Pathology.
. Patients must have:
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Phase I: Number of Grades 1, 2, 3, 4, and/or 5 and Type of Serious and/or Non-serious Toxicities Experienced by Participants at Each Dose Level
Timeframe: from the start of cyclophosphamide, through the first follow-up evaluation (6 weeks [± 2 weeks]) following administration of the cell product) until off study, whichever comes first, an average of 2.3 months
2
Phase I: Percentage of Participants Who Experienced a Grade 3, 4 and/or 5 Serious Dose-Limiting Toxicity (DLT) Reported With Type at Each Dose Level
Timeframe: At the time of cell infusion and end two weeks after cell infusion, an average of one month
3
Phase II: Percentage of Participants With a Clinical Response (Complete Response (CR) + Partial Response (PR) Reported With 80% Confidence Interval
Timeframe: 6 weeks and 12 weeks following administration of the cell product, then every 3 months x3, then every 6 months x 2 years, then per principal investigator (PI) discretion
4
Phase II: Percentage of Participants With a Clinical Response (Complete Response (CR) + Partial Response (PR) Reported With 95% Confidence Interval
Timeframe: 6 weeks and 12 weeks following administration of the cell product, then every 3 months x3, then every 6 months x 2 years, then per principal investigator (PI) discretion
previously received standard systemic therapy for their advanced cancer and have been either non-responders or have recurred, specifically:
declined standard treatment.
. Patients with 3 or fewer brain metastases that are \< 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.
. Age greater than or equal to 18 years and less than or equal to 72 years.
Exclusion criteria
. Women of child-bearing potential who are pregnant or breastfeeding because of the potentially dangerous effects of the treatment on the fetus or infant.
. Concurrent systemic steroid therapy.
. Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses.
. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
. Concurrent opportunistic infections (The experimental treatment being evaluated in this protocol depends on an intact immune system. Patients who have decreased immune competence may be less responsive to the experimental treatment and more susceptible to its toxicities.)
. History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.
. History of coronary revascularization or ischemic symptoms.
. For select patients with a clinical history prompting cardiac evaluation: last known left ventricular ejection fraction (LVEF) less than or equal to 45%.