A Study of ALT-801 in Patients With Bacillus Calmette-Guerin (BCG) Failure Non-Muscle Invasive Bladder Cancer

This is a Phase Ib/II, open-label, multi-center and competitive enrollment study of ALT-801 combined with gemcitabine for patients who have BCG failure (defined as refractory, relapsing or intolerant), non-muscle invasive bladder cancer and refuse or are not medically fit to undergo a radical cystectomy recommended by the participating urologist as the standard next therapy per urologic guidelines. The purpose of this study is to confirm the safety and tolerability of a well-tolerated dose level of ALT-801, to determine the Recommended Dose level (RD) and characterize the immunogenicity of ALT-801 combined with gemcitabine in treated patients. The anti-tumor responses will also be assessed.

Bladder cancer is the fifth most common cancer in the United States with an estimated 71,000 new cases and approximately 14,000 deaths in 2009. Bladder cancer is also the costliest to treat per patient of all cancers, with annual direct medical expenditures in excess of $3.7 billion in the United States. This is largely because approximately 70% of all new cases of bladder cancer present as non-muscle invasive bladder cancer (NMIBC), which tends to recur, requiring repeated interventions and long-term follow-up.

Altor Bioscience Corp. has developed a tumor-targeted IL-2 fusion protein, ALT-801, comprising human recombinant IL-2 genetically linked to a TCR domain capable of binding a tumor associated human p53 peptide presented in the context of HLA-A2.

ALT-801 will be evaluated as to whether it can prevent disease progression and allow for bladder preservation to maintain the quality of life for patients with BCG failure, defined as refractory, relapsing or intolerant, non-muscle invasive bladder cancer who refuse or are not medically fit to undergo a radical cystectomy recommended by the participating urologist as the standard next therapy per urologic guidelines.

Eligibility Criteria:
ENTRY CRITERIA:

DISEASE CHARATERISTICS:

* Histologically confirmed high-risk (high grade Ta, T1 or carcinoma in situ, tumor \>4 cm or multi-focal) transitional cell carcinoma s/p TURBT with no remaining resectable disease within 4 weeks of study entry
* Intolerant of treatment with BCG or failure (refractory or relapsing) of at least one prior treatment with BCG
* Refuse or intolerant of a radical cystectomy
* No Evidence of regional and/or distant metastasis

PRIOR/CONCURRENT THERAPY:

* No concurrent radiotherapy, other chemotherapy, or other immunotherapy
* No scheduled radiotherapy, chemotherapy, other immunotherapy, or surgery before the scheduled response evaluation
* Must have recovered from side effects of prior treatments
* No concurrent use of other investigational agents

PATIENT CHARACTERISTICS:

Age

• ≥ 18 years

Performance Status

• ECOG 0, 1, or 2

Bone Marrow Reserve

* Absolute neutrophil count (AGC/ANC) ≥ 1,000/uL
* Platelets ≥ 100,000/uL
* Hemoglobin ≥ 8 g/dL

Renal Function

• Glomerular Filtration Rate (GFR) ≥ 50mL/min

Hepatic Function

* Total bilirubin ≤ 2.0 X ULN
* AST, ALT, ALP ≤ 3.0 X ULN

Cardiovascular

* No congestive heart failure \< 6 months
* No severe/unstable angina pectoris \< 6 months
* No myocardial infarction \< 6 months
* No history of ventricular arrhythmias
* No NYHA Class \> II CHF
* No uncontrollable supraventricular arrhythmias
* No history of a ventricular arrhythmia
* No other clinical signs of severe cardiac dysfunction
* Normal Transthoracic Echocardiogram (TTE) is required for patients who have history of EKG abnormalities, CHF, coronary artery disease or other cardiac disease, or have history of having received adriamycin or doxorubicin
* No patients with a left ventricular ejection fraction (LVEF) of less than 50%

Pulmonary

• Normal clinical assessment of pulmonary function

Other

* Negative serum pregnancy test if female and of childbearing potential
* Women who are not pregnant or nursing
* Subjects, both females and males, with reproductive potential must agree to use effective contraceptive measures for the duration of the study
* No known autoimmune disease other than corrected hypothyroidism
* No known prior organ allograft or allogeneic transplantation
* Not HIV positive
* No active systemic infection requiring parenteral antibiotic therapy
* No ongoing systemic steroid therapy required
* No history or evidence of uncontrollable CNS disease
* No psychiatric illness/social situation
* No other illness that in the opinion of the investigator would exclude the subject from participating in the study
* Must provide informed consent and HIPAA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations