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|NCT03412877 : Administration of Autologous T-Cells Genetically Engineered to Express T-Cell Receptors Reactive Against Mutated Neoantigens in People With Metastatic Cancer|
|Ages||Min: 18 Years Max: 70 Years|
- INCLUSION CRITERIA:
- Measurable solid cancer with at least one lesion that is resectable for TIL generation
with minimal morbidity plus at least one other lesion that can be measured that falls
into one of four cohorts:
1. gastrointestinal and genitourinary cancers
2. breast and ovarian, and other solid cancers
3. non-small cell lung cancer (NSCLC)
- Note: Metastatic disease is required for cohorts 1-3, but not required for
- Note: NSCLC includes but is not limited to squamous cell carcinoma,
adenosquamous carcinoma or adenocarcinomas. Neuroendocrine tumors are not
- Refractory to approved standard systemic therapy. Specifically:
- Patients with metastatic colorectal cancer must have received oxaliplatin or
- Patients with breast and ovarian cancer must be refractory to both 1st line and
2nd line treatments.
- Patients with NSCLC must have received at least one platinum-based chemotherapy
regimen and at least one FDA approved targeted treatment (when appropriate).
- Patients with glioblastoma must have progression of disease after radiotherapy
(including patients that undergo surgery for recurrent disease and are rendered
NED). This includes recurrent GBM after receiving all standard first-line
treatment, including surgery (if feasible due to neurosurgical and
neuro-anatomical considerations) and adjuvant radiotherapy +/- chemotherapy.
- For cohorts 1-3, patients with 3 or fewer brain metastases that are less than 1 cm in
diameter and asymptomatic are eligible. Lesions that have been treated with
stereotactic radiosurgery must be clinically stable for 1 month after treatment for
the patient to be eligible. Patients with surgically resected brain metastases are
- For cohorts 1-3, clinical performance status of ECOG 0 or 1.
- For cohort 4, (glioblastoma), patients must have Karnofsky performance status of
greater than or equal to 60.
- For cohort 4 only (glioblastoma), patients must either not be receiving steroids, or
be on a stable dose of steroids for at least five days prior to registration.
- Age greater than or equal to 18 years and less than or equal to 70 years.
- Willing to sign a durable power of attorney.
- Patients of both genders must be willing to practice birth control during treatment
and for four months after treatment.
- Able to understand and sign a written informed consent document.
- Seronegative for HIV antibody. (The experimental treatment being evaluated in
this protocol depends on an intact immune system. Patients who are HIV
seropositive can have decreased immune competence and thus may be less responsive
to the experimental treatment and more susceptible to its toxicities.)
- Seronegative for active hepatitis B, and seronegative for hepatitis C antibody.
If hepatitis C antibody test is positive, then patient must be tested for the
presence of antigen by RT-PCR and be HCV RNA negative.
- Absolute neutrophil count > 1000/mm^3 without support of filgrastim
- Normal WBC (> 3000/mm^3).
- Hemoglobin > 8.0 g/dl. Subjects may be transfused to reach this cut-off.
- Platelet count > 100,000/mm^3
- Serum ALT/AST < 5.0 x ULN
- Serum creatinine less than or equal to 1.6 mg/dl.
- Total bilirubin less than or equal to 2.0 mg/dl, except in patients with
Gilbert's Syndrome, who must have a total bilirubin less than or equal to 3.0
- More than four weeks must have elapsed since any prior systemic therapy at the time
the patient receives the preparative regimen, and patients' toxicities must have
recovered to a grade 1 or less. Patients may have undergone minor surgical procedures
within the past three weeks, as long as all toxicities have recovered to grade 1 or
- For cohort 3, more than two weeks must have elapsed since any prior palliation for
major bronchial occlusion or bleeding at the time the patient receives the preparative
regimen, and patient s toxicities must have recovered to a grade 1 or less.
- For cohort 4, patients must be at least four weeks from radiation therapy.
Additionally, patients must be at least six weeks from nitrosoureas, four weeks from
temozolomide, three weeks from procarbazine, two weeks from vincristine and four weeks
from last bevacizumab administration. Patients must be at least four weeks from other
cytotoxic therapies not listed above and two weeks for non-cytotoxic agents (e.g.,
interferon) including investigative agents.
- Subjects must be co-enrolled in protocol 03-C-0277.
- Women of child-bearing potential who are pregnant or breastfeeding because of the
potential effects of the treatment on the fetus or infant.
- Systemic steroid therapy required, except for patients with glioblastoma (cohort 4).
- Active systemic infections requiring anti-infective treatment, coagulation disorders
or any other active or uncompensated major medical illnesses.
- For cohort 3, any major bronchial occlusion or bleeding not amenable to palliation.
- For cohort 4, clinically significant hemorrhagic or ischemic stroke, including
transient ischemic attacks and other central nervous system bleeding in the preceding
6 months that were not related to glioma surgery. History of prior intratumoral
bleeding is not an exclusion criterion; however, patients with a history of prior
intratumoral bleeding, will need to undergo a non-contrast head CT to exclude acute
- 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
- History of severe immediate hypersensitivity reaction to cyclophosphamide,
fludarabine, or aldesleukin.
- History of coronary revascularization or ischemic symptoms.
- Any patient known to have an LVEF less than or equal to 45%.
- Documented LVEF less than or equal to 45% tested in patients:
- Age greater than or equal to 65 years
- With clinically significant atrial and/or ventricular arrhythmias including but
not limited to: atrial fibrillation, ventricular tachycardia, second- or
third-degree heart block or have a history of ischemic heart disease and/or chest
- Clinically significant patient history which in the judgment of the PI would
compromise the patients' ability to tolerate high-dose aldesleukin. (Note: At the
discretion of the PI, patients enrolled in cohort 3 may receive low-dose aldesleukin.)
- Documented FEV1 less than or equal to 50% predicted tested in patients with:
- A prolonged history of cigarette smoking (approximately 20 packs/year within the
past two years).
- Symptoms of respiratory dysfunction
- Patients who are receiving any other investigational agents.
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