Clinical trial NCT02070406 (phase 1, status: terminated)
Conditions: unspecified adult solid tumor, protocol specific
ICD codes: H01.009, H02.209, H02.009, H02.109, H04.209, H05.409, H10.509
Drugs: cyclophosphamide, fludarabine phosphate
SMILES: ClCCN(CCCl)P1(=O)NCCCO1, NC1=NC(F)=NC2=C1N=CN2[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O
Reason stopped: 
    low accrual
  
Eligibility criteria:

        Inclusion Criteria:

          -  Stage IV or locally advanced cancers for which no alternative therapies with proven
             survival advantage are available

          -  At least 1 lesion amenable for outpatient biopsies; this should be a cutaneous or
             palpable metastatic site or a deeper site accessible by image-guided biopsy that is
             deemed safe to access by the treating physicians and interventional radiologists;
             patients without accessible lesions for biopsy but with prior tissue available from
             metastatic disease would be eligible at the investigator's discretion

          -  NY-ESO-1 positive malignancy by immunohistochemistry (IHC) utilizing commonly
             available NY-ESO-1 antibodies

          -  Human leukocyte antigen (HLA)-A*0201 (HLA-A2.1) positivity by molecular subtyping

          -  Life expectancy greater than 3 months assessed by a study physician

          -  A minimum of one measurable lesion defined as:

               -  Meeting the criteria for measurable disease according to Response Evaluation
                  Criteria in Solid Tumors (RECIST)

               -  Skin lesion(s) selected as non-completely biopsied target lesion(s) that can be
                  accurately measured and recorded by color photography with a ruler to document
                  the size of the target lesion(s)

          -  No restriction based on prior treatments

          -  Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

          -  Absolute neutrophil count >= 1.5 x 10^9 cells/L

          -  Platelets >= 100 x 10^9/L

          -  Hemoglobin >= 10 g/dL

          -  Aspartate and alanine aminotransferases (AST, ALT) =< 2.5 x upper limit of normal
             (ULN) (=< 5 x ULN, if documented liver metastases are present)

          -  Total bilirubin =< 2 x ULN (except patients with documented Gilbert's syndrome)

          -  Creatinine < 2 mg/dl (or a glomerular filtration rate > 60)

          -  Must be willing and able to accept two leukapheresis procedures

          -  Must be willing and able to provide written informed consent

        Exclusion Criteria:

          -  Previously known hypersensitivity to any of the agents used in this study

          -  Received systemic treatment for cancer, including immunotherapy, within one month
             prior to initiation of dosing within this protocol

          -  History of, or significant evidence of risk for, chronic inflammatory or autoimmune
             disease (eg, Addison's disease, multiple sclerosis, Graves' disease, Hashimoto's
             thyroiditis, inflammatory bowel disease, psoriasis, rheumatoid arthritis, systemic
             lupus erythematosus, hypophysitis, pituitary disorders, etc.); patients will be
             eligible if prior autoimmune disease is not deemed to be active (e.x. fibrotic damage
             of the thyroid after thyroiditis or its treatment, with stable thyroid hormone
             replacement therapy); vitiligo will not be a basis for exclusion

          -  History of inflammatory bowel disease, celiac disease, or other chronic
             gastrointestinal conditions associated with diarrhea or bleeding, or current acute
             colitis of any origin

          -  Potential requirement for systemic corticosteroids or concurrent immunosuppressive
             drugs based on prior history or received systemic steroids within the last 4 weeks
             prior to enrollment (inhaled or topical steroids at standard doses are allowed)

          -  Human immunodeficiency virus (HIV) seropositivity or other congenital or acquired
             immune deficiency state, which would increase the risk of opportunistic infections and
             other complications during chemotherapy-induced lymphodepletion; if there is a
             positive result in the infectious disease testing that was not previously known, the
             patient will be referred to their primary physician and/or infectious disease
             specialist

          -  Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would
             increase the likelihood of hepatic toxicities from the chemotherapy conditioning
             regimen and supportive treatments; if there is a positive result in the infectious
             disease testing that was not previously known, the patient will be referred to their
             primary physician and/or infectious disease specialist

          -  Dementia or significantly altered mental status that would prohibit the understanding
             or rendering of informed consent and compliance with the requirements of this protocol

          -  Clinically active brain metastases; radiological documentation of absence of active
             brain metastases at screening is required for all patients; prior evidence of brain
             metastasis successfully treated with surgery or radiation therapy will not be
             exclusion for participation as long as they are deemed under control at the time of
             study enrollment

          -  Pregnancy or breast-feeding; female patients must be surgically sterile or be
             postmenopausal for two years, or must agree to use effective contraception during the
             period of treatment and 6 months after; all female patients with reproductive
             potential must have a negative pregnancy test (serum/urine) within 14 days from
             starting the conditioning chemotherapy; the definition of effective contraception will
             be based on the judgment of the study investigators

          -  Since IL-2 is administered following cell infusion:

               -  Patients will be excluded if they have a history of clinically significant
                  electrocardiogram (ECG) abnormalities, symptoms of cardiac ischemia or
                  arrhythmias and have a left ventricular ejection fraction (LVEF) < 45% on a
                  cardiac stress test (stress thallium, stress multi gated acquisition (MUGA) scan,
                  dobutamine echocardiogram, or other stress test)

               -  Similarly, patients who are 50 years old with a baseline LVEF < 45% will be
                  excluded

               -  Patients with ECG results of any conduction delays (PR interval > 200 ms,
                  corrected QT interval [QTC] > 480 ms), sinus bradycardia (resting heart rate < 50
                  beats per minute), sinus tachycardia (heart rate > 120 beats per minute) will be
                  evaluated by a cardiologist prior to starting the trial; patients with any
                  arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy
                  (defined as > 20 PVCs per minute), ventricular tachycardia, 3rd degree heart
                  block will be excluded from the study unless cleared by a cardiologist

               -  Patients with pulmonary function test abnormalities as evidenced by a forced
                  expiratory volume of the lung in 1 second (FEV1)/forced vital capacity (FVC) <
                  70% of predicted for normality will be excluded

          -  Evidence of diverticulitis at baseline, including evidence limited to computed
             tomography (CT) scan only