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

A Phase Ib/II 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.

Study Overview

• Status: Terminated
• Conditions: Non-muscle Invasive Bladder Cancer
• Intervention / Treatment: Biological: ALT-801; Drug: Gemcitabine

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.

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.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University Of Alabama Comprehensive Cancer Center
  • California
    • Sacramento, California, United States, 95817
      • University of California Davis
  • Florida
    • Orlando, Florida, United States, 32806
      • UF Health Center at Orlando Health
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Science Center
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 0.06 mg/kg ALT-801 with 1000 mg/m^2 Gemcitabine; ALT-801 at 0.06 mg/kg with Gemcitabine at 1000 mg/m^2	Biological: ALT-801; Intravenous infusion: 2 treatment courses and 1 maintenance course; on Day 3, 5, 8 and 15 of each course.; Other Names: c264scTCR-IL2; Drug: Gemcitabine; Intravenous infusion: 2 treatment courses and 1 maintenance course; on Day 1 and 8 of each course.
Experimental: 0.08 mg/kg ALT-801 with 1000 mg/m^2 Gemcitabine; ALT-801 at 0.08 mg/kg with Gemcitabine at 1000 mg/m^2	Biological: ALT-801; Intravenous infusion: 2 treatment courses and 1 maintenance course; on Day 3, 5, 8 and 15 of each course.; Other Names: c264scTCR-IL2; Drug: Gemcitabine; Intravenous infusion: 2 treatment courses and 1 maintenance course; on Day 1 and 8 of each course.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Profile	Confirmation of the safety and tolerability (dose limiting toxicity count) of ALT-801 combined with gemcitabine.	12 weeks
Disease Response Rate	The response rate was calculated as the ratio of the number of patients who demonstrated a complete response (by RECIST v1.1) divided by the number of patients evaluable for response. A complete response was defined as having negative bladder biopsy results.	From start of study treatment to up to 13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Response	Duration of response was defined as the time from the date of first complete response (by RECIST v1.1) to the date of disease progression (by RECIST v1.1) or death (from any cause), whichever occured first. A complete response was defined as having negative bladder biopsy results. Disease progression by RECIST v1.1 is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression.	From confirmed complete response to up to 3 years
Progression-free Survival	The progression-free survival was defined as the time from the start of study treatment to first documentation of objective tumor progression or disease recurrence (by RECIST v1.1). Disease progression by RECIST v1.1 is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression.	From start of study treatment to up to 3 years
Event-free Survival	The event-free survival was defined as the time from the start of study treatment to first documentation of objective tumor progression (by RECIST v1.1), disease recurrence, bladder resection or irradiation, other anti-bladder cancer therapy, or to death due to any cause, which ever came first. Disease progression by RECIST v1.1 is defined as at least a 20% increase in the sum of diameters of target lesions in reference to the smallest sum on study and an absolute increase of at least 5 mm; the appearance of any new lesions is also considered progression.	From start of study treatment to up to 3 years
Overall Survival	OS was defined as the time from start of study treatment to death resulting from any cause.	From start of study treatment to up to 3 years

Collaborators and Investigators

• Sponsor: Altor BioScience
• Collaborators: James and Esther King Biomedical Research Program
• Investigators: Study Chair: Hing C Wong, PhD, Altor BioScience

Study record dates

Study Major Dates

• Study Start (Actual): March 30, 2012
• Primary Completion (Actual): March 8, 2018
• Study Completion (Actual): March 8, 2018

Study Registration Dates

• First Submitted: June 19, 2012
• First Submitted That Met QC Criteria: June 19, 2012
• First Posted (Estimated): June 21, 2012

Study Record Updates

• Last Update Posted (Actual): July 19, 2024
• Last Update Submitted That Met QC Criteria: July 18, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: immunotherapy; cancer; bladder cancer; urothelial cancer; targeted; interleukin-2; gemcitabine; antitumor; TCR; T-cell receptor; p53; p53 gene; p53 tumor supressor protein; HLA-A2 positive; HLA-A*0201/p53 aa264-272; HLA complex; relapsed; refractory; BCG; carcinoma in situ; transitional cell carcinoma; non-muscle invasive; multi-focal
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Urinary Bladder Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Urinary Bladder Neoplasms; Non-Muscle Invasive Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Gemcitabine
• Other Study ID Numbers: CA-ALT-801-01-12

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO