- Solid cancer that can be measured, that falls into one of four cohorts: (1)
gastrointestinal and genitourinary cancers; (2) breast, ovarian, and other solid
cancers; (3) non-small cell lung cancer (NSCLC); and, (4) glioblastoma.
--Note: Metastatic disease is required for Cohorts 1-3, but not required for cohort 4.
NSCLC includes but is not limited to squamous cell carcinoma, adenosquamous carcinoma
or adenocarcinomas. Neuroendocrine tumors are not eligible.
- - Confirmation of diagnosis of cancer by the NCI Laboratory of Pathology.
- - Refractory to approved standard systemic therapy.
- - Patients with metastatic colorectal cancer must have received oxaliplatin or
- - Patients with breast and ovarian cancer must be refractory to both first and
second 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
This includes recurrent glioblastoma 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 or equal
to 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
- - Age greater than or equal to 18 years and less than or equal to 70 years.
- - For Cohorts 1-3: clinical performance status of ECOG 0 or 1.
- - For cohort 4: Patients must have Karnofsky performance status greater than or equal to
- - Patients of both genders must be willing to practice birth control from the time of
enrollment on this studyand for four months after treatment.
- - Women of child-bearing potential must have a negative pregnancy test because of the
potentially dangerous effects of the treatment on the fetus.
- - Serology:
- Seronegative for HIV antibody.
(The experimental treatment being evaluated in
this protocol depends on an intact immune system. Patients who are HIV
seropositive may have decreased immune-competence and thus be less responsive to
the experimental treatment and more susceptible to its toxicities.)
- - Seronegative for hepatitis B antigen, 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.
- - Hematology:
- ANC > 1000/mm^3 without the support of filgrastim
- WBC greater than or equal to 3000/mm^3
- Platelet count greater than or equal to 100,000/mm^3
- Hemoglobin > 8.0 g/dl.
Subjects may be transfused to reach this cut-off.
- - Chemistry:
- Serum ALT/AST less than or equal to 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 completion of any prior systemic therapy
at the time of enrollment .
Note: Patients may have undergone minor surgical procedures or limited field radiotherapy
within the four weeks prior to enrollment, as long as related major organ toxicities have
recovered to grade 1 or less.
- - 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.
- - For Cohort 4: Patients must either not be receiving steroids, or be on a stable dose
of steroids, for at least five days prior to registration.
- - Ability of subject to understand and the willingness to sign a written informed
- - Willing to sign a durable power of attorney.
- - Subjects must be co-enrolled on protocol 03-C-0277.
- - 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, 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
six months that were not related to glioma surgery.
Note: 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 bleeding.
- - Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease
- - For Arm 2: History of major organ autoimmune disease.
Note: Patients with a history of major organ autoimmune disease may be enrolled on Arm 1 if
all other eligibility criteria are met.
-For Arm 2: Grade 3 or 4 major organ irAEs following treatment with anti-PD-1/PD-L1,
including but not limited to myocarditis and pneumonitis.
Note: Patients with grade 3 or 4 major organ irAEs may be enrolled on Arm 1 if all other
eligibility criteria are met.
-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
- - History of severe immediate hypersensitivity reaction to cyclophosphamide,
fludarabine, or aldesleukin.
- - For Cohorts 1, 2, or 4: Clinically significant patient history which in the judgment
of the Principal Investigator (PI) would compromise the patients' ability to tolerate
Note: At the discretion of the PI, patients enrolled in cohort 3 may receive low-dose
- - 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
- Documented FEV1 less than or equal to 50% predicted tested in patients with:
- A prolonged history of cigarette smoking (greater than or equal to 20 pack-year
smoking history, within the past two years).
- - Symptoms of respiratory dysfunction
- Patients who are receiving any other investigational agents.