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

This study is ongoing, but not recruiting participants.
James and Esther King Biomedical Research Program
Information provided by (Responsible Party):
Altor Bioscience Corporation Identifier:
First received: June 19, 2012
Last updated: January 23, 2017
Last verified: January 2017
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.

Condition Intervention Phase
Non-muscle Invasive Bladder Cancer
Biological: ALT-801
Drug: Gemcitabine
Phase 1
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase Ib/II Study of ALT-801 in Patients With Bacillus Calmette-Guerin (BCG) Failure Non-muscle Invasive Bladder Cancer

Resource links provided by NLM:

Further study details as provided by Altor Bioscience Corporation:

Primary Outcome Measures:
  • Safety Profile [ Time Frame: 12 weeks ]

    For Phase Ib & II

    Number and severity of treatment related AEs that occur or worsen after the first dose of study treatment

  • Tolerability of ALT-801 combined with gemcitabine and designation of the Recommended Dose level (RD) [ Time Frame: 12 weeks ]

    For phase Ib only

    Tolerability of a well-tolerated dose level of ALT-801 combined with gemcitabine and designation of the recommended dose level (RD)

  • Clinical Benefit [ Time Frame: up to 13 weeks ]

    For Phase Ib & II

    Number of participants with a complete response

Secondary Outcome Measures:
  • Duration of response [ Time Frame: up to 3 years ]

    For Phase Ib & II

    All responding patients will be followed every 3 months during years 1 and 2 and every 6 month during year 3 to determine their duration of response

  • Progression-free survival [ Time Frame: up to 3 years ]

    For Phase Ib & II

    All patients receiving one complete dose of ALT-801 will be followed every 3 months during years 1 and 2 and every 6 month during year 3 to determine their progression-free survival

  • Event free survival [ Time Frame: up to 3 years ]

    For Phase Ib & II

    All patients receiving one complete dose of ALT-801 will be followed every 3 months during years 1 and 2 and every 6 month during year 3 to determine their event-free survival

  • Overall survival [ Time Frame: up to 3 years ]

    For Phase Ib & II

    All patients receiving one complete dose of ALT-801 will be followed every 3 months during years 1 and 2 and every 6 month during year 3 to determine their overall survival

  • Immunogenicity of ALT-801 [ Time Frame: 8 weeks ]

    For Phase Ib & II

    Measures the anti-ALT-801 and IL-2 neutralizing effects

  • Tumor Typing [ Time Frame: 1 month ]

    For Phase Ib & II

    Assess the relationship between the tumor presentation of HLA-A*0201/p53 aa 264-272 complexes and the safety, immune response and clinical benefit of study treatment

Estimated Enrollment: 52
Study Start Date: April 2012
Estimated Study Completion Date: March 2018
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Gemcitabine in combination with ALT-801 Biological: ALT-801
Intravenous infusion: 2 treatment courses and 1 maintenance course; on Day 3, 5, 8 and 15 of each course.
Other Name: c264scTCR-IL2
Drug: Gemcitabine
Intravenous infusion: 2 treatment courses and 1 maintenance course; on Day 1 and 8 of each course.

  Hide Detailed Description

Detailed Description:

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.

NMIBC tumors are usually treated by surgical resection and intravesical chemotherapy and immunotherapy. Immunotherapy usually consists of intravesical administration of Bacillus Calmette-Guerin (BCG). Recent studies suggest that BCG is superior in terms of efficacy and decreasing disease recurrence compared to other therapies. Although the mechanism of action for BCG therapy leading to clinical efficacy is unclear, macrophages, T lymphocytes and natural killer (NK) cells are implicated as the critical mediators of the anti-tumor immune response. Consequently, BCG is associated with significant toxicity, and approximately 20% of patients fail to complete the course of therapy. In addition, as many as 30% of patients either fail to respond to therapy or suffer disease recurrence within 5 years. Of these, 30% will eventually die of bladder cancer and 50% will undergo radical cystectomy. Thus, a novel therapy, either as first-line or salvage therapy, is desperately needed for NMIBC to prevent disease progression and allow for bladder preservation to preserve quality of life of patients. Alternatively, a novel therapy that moderates the significant and often treatment-limiting side effects of BCG immunotherapy is also warranted.

Additionally, immunotherapy is a well-established approach for treating other cancer types. One strategy that has received attention is treatment with cytokines such as IL-2 to enhance anti-tumor immunity. IL-2 has been implicated as playing a pivotal role in the efficacy of BCG treatment of patients with NMIBC. Studies have demonstrated that a direct IL-2 intervention could be of benefit to patients who are refractory or resistant to BCG treatment. Unfortunately, the considerable toxicity associated with this treatment makes it difficult to achieve an effective dose at the site of the tumor and limits the population that can be treated. Thus, there is a critical need for innovative strategies that enhance the effects of IL-2, to reduce its toxicity without compromising clinical benefit, and to treat other diagnoses including NMIBC.

Recombinant human IL-2 (rhIL-2; Proleukin®) is an approved agent for the treatment of adults with metastatic melanoma and renal cell carcinoma (RCC). In particular, high dose intravenous IL-2 treatment has demonstrated durable objective response rate in these indications. However, the major toxicities associated with this regimen have precluded its widespread application.

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. Animal studies have indicated that ALT-801 could be useful in a therapeutic approach for activating immune effector cells, bringing together effector cells and tumor cells and stimulating immune cell-mediated activity. In addition, pre-clinical studies of ALT-801 in an NMIBC tumor model indicate that ALT-801 monotherapy may provide clinical benefit to patients with NMIBC. Various mouse xenograft models also demonstrate that ALT-801 increases the efficacy but lessens the side effects of high-dose rhIL-2.

Moreover, the results of a concluded phase I clinical study of a monotherapy with ALT-801 in patients with metastatic malignancies indicate that ALT-801 given daily for two 4-day cycles at a dose level of 0.04 mg/kg is well tolerated, exhibits a favorable PK drug profile and immunological potency, and provides clinical benefit in cancer patients. Also, a higher dosing level (0.08 mg/kg) of ALT-801 was associated with better clinical benefit.

Based on these findings, 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.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No



  • 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


  • 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



• ≥ 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


  • 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%


• Normal clinical assessment of pulmonary function


  • 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
  Contacts and Locations
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Please refer to this study by its identifier: NCT01625260

United States, Alabama
University of Alabama Comprehensive Cancer Center
Birmingham, Alabama, United States, 35294
United States, California
University of California Davis
Sacramento, California, United States, 95817
United States, Florida
UF Health Center at Orlando Health
Orlando, Florida, United States, 32806
United States, Oklahoma
University of Oklahoma Health Science Center
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
UPMC Cancer Center
Pittsburgh, Pennsylvania, United States, 15232
Sponsors and Collaborators
Altor Bioscience Corporation
James and Esther King Biomedical Research Program
Study Chair: Hing C Wong, PhD Altor Bioscience Corporation
  More Information

Responsible Party: Altor Bioscience Corporation Identifier: NCT01625260     History of Changes
Other Study ID Numbers: CA-ALT-801-01-12
Study First Received: June 19, 2012
Last Updated: January 23, 2017
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Altor Bioscience Corporation:
non-muscle invasive
T-cell receptor
p53 gene
p53 tumor supressor protein
urothelial cancer
bladder cancer
HLA-A2 positive
HLA-A*0201/p53 aa264-272
HLA complex
carcinoma in situ
transitional cell carcinoma

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Urinary Bladder Diseases
Urologic Diseases
BCG Vaccine
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Adjuvants, Immunologic
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents processed this record on May 25, 2017