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

This study is currently recruiting participants.
Verified January 2014 by Altor Bioscience Corporation
Sponsor:
Collaborator:
Florida Department of Health James and Esther King Biomedical Research
Information provided by (Responsible Party):
Altor Bioscience Corporation
ClinicalTrials.gov Identifier:
NCT01625260
First received: June 19, 2012
Last updated: January 27, 2014
Last verified: January 2014
  Purpose

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: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: Yes ]

    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 ] [ Designated as safety issue: No ]

    For Phase Ib & II

    Number of participants with a complete response



Secondary Outcome Measures:
  • Duration of response [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]

    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 ] [ Designated as safety issue: No ]

    For Phase Ib & II

    All enrolled patients 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 ] [ Designated as safety issue: No ]

    For Phase Ib & II

    All enrolled patients 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 ] [ Designated as safety issue: No ]

    For Phase Ib & II

    All enrolled patients 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 ] [ Designated as safety issue: No ]

    For Phase Ib & II

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


  • Tumor Typing [ Time Frame: 1 month ] [ Designated as safety issue: No ]

    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: July 2014
Estimated Primary Completion Date: April 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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/1.73m^2

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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01625260

Locations
United States, Alabama
University of Alabama Comprehensive Cancer Center Recruiting
Birmingham, Alabama, United States, 35294
Contact: Dayle Craig    205-975-8080    dc0350@uab.edu   
Principal Investigator: Guru P Sonpavde, MD         
United States, California
University of California Davis Recruiting
Sacramento, California, United States, 95817
Contact: Frances Lara    916-734-8134    francis.lara@ucdmc.ucdavis.edu   
Principal Investigator: Chong-xian Pan, MD         
United States, Florida
MD Anderson Cancer Center Orlando Active, not recruiting
Orlando, Florida, United States, 32806
Martin Health System Recruiting
Stuart, Florida, United States, 34994
Contact: Lucinda Fasig, RN    772-223-5945 ext 3776    lucinda.fasig@martinhealth.org   
Principal Investigator: Guillermo Abesada-Terk, Jr., M.D.         
United States, North Carolina
Carolinas Medical Center Recruiting
Charlotte, North Carolina, United States, 28203
Contact: Tesa Adams, RN, CCRP    704-446-5145    Tesa.Adams@carolinashealthcare.org   
Principal Investigator: John Mahoney, M.D.         
United States, Oklahoma
University of Oklahoma Health Science Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Allison McClure, RN    405-271-8001 ext 48442    allison-mcclure@ouhsc.edu   
Principal Investigator: Puneet Sindhwani, MD         
United States, Pennsylvania
UPMC Cancer Center Recruiting
Pittsburgh, Pennsylvania, United States, 15232
Contact: Diana Long, RN    412-647-8258    longdl@upmc.edu   
Principal Investigator: Rahul Parikh, MD         
Sponsors and Collaborators
Altor Bioscience Corporation
Florida Department of Health James and Esther King Biomedical Research
Investigators
Principal Investigator: Charles J Rosser, M.D. MD Anderson Cancer Center Orlando
  More Information

No publications provided

Responsible Party: Altor Bioscience Corporation
ClinicalTrials.gov Identifier: NCT01625260     History of Changes
Other Study ID Numbers: CA-ALT-801-01-12
Study First Received: June 19, 2012
Last Updated: January 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Altor Bioscience Corporation:
cancer
immunotherapy
targeted
non-muscle invasive
interleukin-2
antitumor
TCR
T-cell receptor
p53
p53 gene
p53 tumor supressor protein
urothelial cancer
bladder cancer
HLA-A2 positive
HLA-A*0201/p53 aa264-272
HLA complex
refractory
relapsed
BCG
multi-focal
carcinoma in situ
transitional cell carcinoma
gemcitabine

Additional relevant MeSH terms:
Urinary Bladder Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Urinary Bladder Diseases
Urologic Diseases
BCG Vaccine
Gemcitabine
Adjuvants, Immunologic
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on April 17, 2014