A Study of Intravesical BCG in Combination With ALT-803 in Patients With Non-Muscle Invasive Bladder Cancer

April 11, 2024 updated by: ImmunityBio, Inc.

A Study of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 (N-803) in Patients With Non-Muscle Invasive Bladder Cancer

This is a Phase Ib/IIb, randomized, two-cohort, open-label, multicenter study of intravesical N-803 plus BCG versus BCG alone, in BCG naïve patients with high-grade NMIBC.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

The study includes a dose escalation phase (phase Ib) and an expansion phase (phase IIb).

In the phase Ib, patients will be treated with intravesical N-803 in combination with BCG. The purpose of the phase Ib portion of the study is to evaluate the safety, identify the Maximum Tolerated Dose (MTD) of N-803 and determine the Recommended Dose (RD) level of N-803 in combination with BCG for the phase IIb expansion.

In the phase IIb expansion, patients will be randomized to receive either intravesical N-803 in combination with BCG or BCG alone. Patients will be enrolled into one of two study cohorts (Cohort A and Cohort B). These will be two independent study cohorts, evaluated separately for treatment efficacy.

Study Type

Interventional

Enrollment (Estimated)

596

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Completed
        • University of Alabama at Birmingham
    • Alaska
      • Anchorage, Alaska, United States, 99503
        • Completed
        • Alaska Clinical Research Center
    • Arkansas
      • Little Rock, Arkansas, United States, 72211
        • Completed
        • Arkansas Urology
    • California
      • Irvine, California, United States, 92618
        • Recruiting
        • Hoag Cancer Center
        • Principal Investigator:
          • Jeffrey Bassett, MD, MPH
        • Contact:
      • Los Angeles, California, United States, 90095
      • Sacramento, California, United States, 95817
        • Completed
        • University of California, Davis
      • Sherman Oaks, California, United States, 91411
        • Active, not recruiting
        • Skyline Sherman Oaks
      • Torrance, California, United States, 90505
        • Completed
        • Skyline Urology
    • Connecticut
      • Norwich, Connecticut, United States, 06360
        • Completed
        • Eastern Connecticut Hematology & Oncology Associates
    • Florida
      • Pompano Beach, Florida, United States, 33060
        • Completed
        • Clinical Research Center of Florida
      • Tampa, Florida, United States, 33612
        • Active, not recruiting
        • Moffitt Cancer Center
    • Hawaii
      • Honolulu, Hawaii, United States, 96813
        • Active, not recruiting
        • University of Hawaii Cancer Center
    • Kansas
      • Westwood, Kansas, United States, 66205
        • Completed
        • Kansas University Medical Center
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Completed
        • Karmanos Cancer Institute
    • Nebraska
      • Omaha, Nebraska, United States, 68114
        • Active, not recruiting
        • Adult & Pediatric Urology
    • New Hampshire
      • Lebanon, New Hampshire, United States, 03756
        • Recruiting
        • Dartmouth-Hitchcock Medical Center
        • Contact:
        • Principal Investigator:
          • Einar F Sverrisson, MB
    • New Mexico
      • Albuquerque, New Mexico, United States, 87109
        • Completed
        • Urology Group of New Mexico (AccumetRx Clinical Research)
    • New York
      • Mineola, New York, United States, 11501
        • Active, not recruiting
        • Winthrop University Hospital
      • New York, New York, United States, 10016
      • Poughkeepsie, New York, United States, 12601
        • Recruiting
        • Premier Medical Group of the Hudson Valley
        • Contact:
        • Principal Investigator:
          • Evan Goldfischer, MD
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27278
        • Recruiting
        • University of North Carolina Chapel Hill
        • Contact:
        • Principal Investigator:
          • Marc Bjurlin, DO
      • Raleigh, North Carolina, United States, 27612
        • Recruiting
        • Associated Urologists of North Carolina
        • Contact:
        • Principal Investigator:
          • Mark Jalkut, MD
    • Virginia
      • Richmond, Virginia, United States, 23235
        • Recruiting
        • Virginia Urology
        • Contact:
        • Principal Investigator:
          • Eugene Kramolowsky, MD
    • Washington
      • Seattle, Washington, United States, 98195
        • Completed
        • University of Washington School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. Histologic confirmation of non-muscle invasive bladder cancer of the transitional cell carcinoma high-grade subtype (mixed histology tumors allowed if transitional cell histology is predominant histology).

    1. Cohort A: Histologically confirmed CIS (with or without Ta/T1 disease); Cohort B: Histologically confirmed high-grade papillary disease (Ta/T1 only).
    2. Patients are eligible if the diagnostic biopsy was done within 3 months of treatment start and a cystoscopy demonstrating no resectable disease was done within 90 days of treatment start (residual CIS is acceptable; patients with T1 disease must undergo repeat resection if muscularis propria is not present in each biopsy sample). Patients with high-grade Ta and/or T1 disease should have complete resection before study treatment.
    3. Upper tract imaging within 6 months prior to study entry must not be suspicious for upper tract malignancy.
  2. Currently eligible for intravesical BCG therapy.
  3. Age ≥ 18 years.
  4. Performance status: ECOG performance status of 0, 1, or 2.

  5. BCG-naive disease as defined as either of the following:

    1. Have not received prior intravesical BCG; or
    2. Previously received BCG, but stopped receiving more than 3 years before date of randomization.

  6. Laboratory tests performed within 21 days of treatment start:

    1. Absolute neutrophil count (AGC/ANC) ≥ 1,000/µL
    2. Platelets ≥ 100,000/µL [Patients may be transfused to meet this requirement]
    3. Hemoglobin ≥ 8 g/dL [Patients may be transfused to meet this requirement]
    4. Calculated glomerular filtration rate (GFR*) >40 mL/min or Serum creatinine ≤ 1.5 x ULN
    5. Total bilirubin ≤ 2.0 X ULN
    6. AST, ALT, ALP ≤ 3.0 X ULN
  7. Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction. PFT > 50% FEV1 if clinically indicated by the investigator.
  8. Negative serum pregnancy test if female and of childbearing potential (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized).
  9. Female participants of childbearing potential must adhere to using a medically accepted method of birth control prior to screening and agree to continue its use during the study or be surgically sterilized (e.g., hysterectomy or tubal ligation) and males must agree to use barrier methods of birth control while on study.

  10. Provide signed informed consent and HIPPA authorization and agree to comply with all protocol-specified procedures and follow-up evaluations.

    • using the following Cockcroft-Gault equation to calculate the eGFR for this study: eGFR in mL/min = {(140-age in years) x (weight in kg) x F}/(serum creatinine in mg/dL x 72) Where F =1 if male; and 0.85 if female

Exclusion Criteria

  1. Prior BCG treatment or known hypersensitivity to BCG. Patients who have received more than a single-dose post-operative treatment of mitomycin-C or gemcitabine following the most recent screening TURBT/biopsy are excluded.
  2. Concurrent use of other investigational agents (not including FDA-authorized drugs for the prevention and treatment of COVID-19).
  3. History of or evidence of muscle-invasive, locally advanced, metastatic and/or extravesical bladder cancer or any other cancer within the past 5 years, except: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated stage 1 or 2 cancer from which the patient is currently in complete remission, or stable prostate cancer (under active surveillance or hormone control).
  4. Symptomatic congestive heart failure (CHF), NYHA (New York Heart Association) Class III or IV or other clinical signs of severe cardiac dysfunction.
  5. Severe/unstable angina pectoris, or myocardial infarction within 6 months prior to study entry.
  6. History or evidence of uncontrollable CNS disease.
  7. Known HIV-positive.
  8. Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy.
  9. Concurrent febrile illness, active urinary tract infection, active tuberculosis, a history of hypotension or anaphylactic reactions.
  10. Ongoing chronic systemic steroid therapy required (>10 mg oral prednisone daily or equivalent).
  11. Women who are pregnant or nursing. Female patients of childbearing potential must have a negative pregnancy test and must adhere to using a medically acceptable method of birth control prior to screening and agree to continue its use during the study and for 30 days after the last dose of study drug, or be surgically sterilized (e.g., hysterectomy or tubal ligation). Women of childbearing potential are defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal. Postmenopausal is defined as 12 consecutive months with no menses without an alternative medical cause. Males must agree to use barrier methods of birth control while on study and for 90 days post last dose of study drug.
  12. Psychiatric illness/social situations that would limit compliance with study requirements.
  13. Other illness that in the opinion of the investigator would exclude the patient from participating in this study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: N-803+BCG
(Phase Ib and IIb) for BCG-naive patients
Biological: BCG+N-803

BCG and N-803 will be mixed together (with saline) and administered via intravesical instillation weekly for 6 consecutive weeks for induction. Phase IIb includes maintenance treatment consisting of BCG+N-803 for 3 consecutive weeks at 3, 6, 12, 18, 24,30 and 36 months.

An additional 6 week re-induction of BCG+N-803 for patients with eligible disease at 3 months in phase IIb is included.
Active Comparator: BCG alone
(Phase IIb) for BCG-naive patients
Biological: BCG

BCG will be administered via intravesical instillation weekly for 6 consecutive weeks for induction. Phase IIb includes maintenance treatment consisting of BCG for 3 consecutive weeks at 3, 6, 12, 18, 24, 30 and 36 months.

An additional 6 week re-induction of BCG for patients with eligible disease at 3 months in phase IIb is included.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Complete Response (CR) Rate
Time Frame: 6 Months
For phase IIb patients in Cohort A: compare complete response rate between treatment arms using cystoscopy, confirmatory bladder biopsy and urine cytology.
6 Months
Disease Free Survival (DFS)
Time Frame: 36 Months
For phase IIb patients in Cohort B: compare disease-free survival between treatment arms using cystoscopy, confirmatory bladder biopsy and urine cytology.
36 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Progression-free survival (PFS)
Time Frame: 10 Years
For phase IIb, Cohorts A & B: time from randomization to disease progression or death
10 Years
Overall survival
Time Frame: 10 Years
For phase Ib and IIb: all enrolled patients will be followed for 2 years to determine survival.
10 Years
Disease specific survival
Time Frame: 10 Years
For phase IIb, Cohorts A & B: time from randomization to death resulting from bladder cancer
10 Years
Time to disease worsening
Time Frame: 10 Years
For phase IIb, Cohorts A & B: cystectomy or change in therapy indicative of more advanced disease, including systemic chemotherapy or radiation therapy
10 Years
Time to cystectomy
Time Frame: 10 years
For phase IIb, Cohorts A & B: time from randomization to cystectomy
10 years
Safety Profile: Number and severity of treatment related AEs
Time Frame: 39 Months
For phase Ib and phase IIb Number and severity of treatment related AEs that occur or worsen after the first dose of study treatment.
39 Months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immunogenicity: serum level of anti-N-803 in patient samples
Time Frame: 36 Months
For phase Ib and IIb Measures the serum level of anti-N-803 in patient samples.
36 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

ImmunityBio, Inc.

Investigators

  • Study Director: Bobby Reddy, MD, ImmunityBio, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 21, 2014

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

December 1, 2038

Study Registration Dates

First Submitted

May 13, 2014

First Submitted That Met QC Criteria

May 13, 2014

First Posted (Estimated)

May 15, 2014

Study Record Updates

Last Update Posted (Estimated)

April 15, 2024

Last Update Submitted That Met QC Criteria

April 11, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CA-ALT-803-01-14; QUILT-2.005

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Non-muscle Invasive Bladder Cancer

Clinical Trials on BCG+N-803

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Belgium

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe