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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02138734
Recruitment Status : Recruiting
First Posted : May 15, 2014
Last Update Posted : March 12, 2021
Sponsor:
Information provided by (Responsible Party):
ImmunityBio, Inc.

Tracking Information
First Submitted Date  ICMJE May 13, 2014
First Posted Date  ICMJE May 15, 2014
Last Update Posted Date March 12, 2021
Actual Study Start Date  ICMJE July 21, 2014
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 22, 2019)
  • Complete Response (CR) Rate [ Time Frame: 12 months ]
    For phase IIb patients in Cohort A: compare complete response rate between treatment arms using cystoscopy, confirmatory bladder biopsy and urine cytology.
  • Disease Free Survival (DFS) [ Time Frame: 24 months ]
    For phase IIb patients in Cohort B: compare disease-free survival between treatment arms using cystoscopy, confirmatory bladder biopsy and urine cytology.
Original Primary Outcome Measures  ICMJE
 (submitted: May 13, 2014)
  • Safety Profile [ Time Frame: 48 months ]
    Number and severity ot treatment related AEs that occur or worsen after the first dose of study treatment.
  • MTD Determination and RD Designation [ Time Frame: 9 months ]
    Determine the maximum tolerated dose (MTD) and designate the recommended dose (RD) level for Phase II.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 22, 2019)
  • Progression-free survival (PFS) [ Time Frame: 24 months ]
    For phase IIb, Cohorts A & B: time from randomization to disease progression or death
  • Overall survival [ Time Frame: 24 months ]
    For phase Ib and IIb: all enrolled patients will be followed for 2 years to determine survival.
  • Disease specific survival [ Time Frame: 24 months ]
    For phase IIb, Cohorts A & B: time from randomization to death resulting from bladder cancer
  • Time to disease worsening [ Time Frame: 24 months ]
    For phase IIb, Cohorts A & B: cystectomy or change in therapy indicative of more advanced disease, including systemic chemotherapy or radiation therapy
  • Time to cystectomy [ Time Frame: 24 months ]
    For phase IIb, Cohorts A & B: time from randomization to cystectomy
  • Safety Profile: Number and severity of treatment related AEs [ Time Frame: 48 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: May 13, 2014)
  • Clinical Benefit [ Time Frame: 48 months ]
    Number of patients with an objective, complete response.
  • Pharmacokinetics [ Time Frame: 48 months ]
    For phase Ib and II Area under the plasma concentration-time curve from time zero to infinity (AUC) and the half-life of ALT-803.
  • Biomarkers [ Time Frame: 48 months ]
    Measures the serum and urine levels of IL-2, IL-4, IL-6, IL-10, IFN-gamma and TNF-alpha in treated patients.
  • Molecular Alterations [ Time Frame: 48 months ]
    Measures the molecular changes (angiogenesis, apoptosis and proliferative index) and immune cell infiltration (assessed by immunohistochemistry for immune cells) in treated patients.
  • Immune Cell Assessment [ Time Frame: 48 months ]
    The percentage and numbers of specific immune cell subsets and their phenotypes, including T cells, B cells, and NK cells will be assessed.
  • Immunogenicity [ Time Frame: 48 months ]
    Measures the serum level of anti-ALT-803 in patient samples.
  • Overall Survival [ Time Frame: 24 months ]
    All enrolled patients will have a cystoscopy and urine cytology performed every 3 months for 2 years to determine recurrence-free survival, progression-free survival, overall survival and duration of response.
Current Other Pre-specified Outcome Measures
 (submitted: March 10, 2021)
Immunogenicity: serum level of anti-N-803 in patient samples [ Time Frame: 24 months ]
For phase Ib and IIb Measures the serum level of anti-N-803 in patient samples.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of Intravesical BCG in Combination With ALT-803 in Patients With Non-Muscle Invasive Bladder Cancer
Official Title  ICMJE A Study of Intravesical Bacillus Calmette-Guerin (BCG) in Combination With ALT-803 in Patients With Non-Muscle Invasive Bladder Cancer
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Single arm phase Ib.

Two-arm phase IIb, two-cohort: each randomized 1:1 via randomization scheme stratified by disease and ECOG status.

Cohort A: patients with CIS disease (with or without Ta/T1); planned enrollment = 366 Cohort B: patients with high-grade papillary disease (Ta/T1 only); planned enrollment = 230

Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Non-muscle Invasive Bladder Cancer
Intervention  ICMJE
  • 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 months.

    An additional 6 week re-induction of BCG+N-803 for patients with eligible disease at 3 months in phase IIb is included.

  • 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 months.

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

Study Arms  ICMJE
  • Experimental: N-803+BCG
    (Phase Ib and IIb) for BCG-naive patients
    Intervention: Biological: BCG+N-803
  • Active Comparator: BCG alone
    (Phase IIb) for BCG-naive patients
    Intervention: Biological: BCG
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 22, 2019)
596
Original Estimated Enrollment  ICMJE
 (submitted: May 13, 2014)
18
Estimated Study Completion Date  ICMJE December 2027
Estimated Primary Completion Date December 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 6 weeks 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. 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
  6. Adequate pulmonary function without any clinical sign of severe pulmonary dysfunction. PFT > 50% FEV1 if clinically indicated by the investigator.
  7. Negative serum pregnancy test if female and of childbearing potential (non-childbearing is defined as greater than one year postmenopausal or surgically sterilized).
  8. 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.
  9. 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 are excluded.
  2. Concurrent use of other investigational agents.
  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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Emily Hui, MPH, MBA emily.hui@immunitybio.com
Contact: Liza H Ochoa, BS liza.hochoa@immunitybio.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02138734
Other Study ID Numbers  ICMJE CA-ALT-803-01-14; QUILT-2.005
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party ImmunityBio, Inc.
Study Sponsor  ICMJE ImmunityBio, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Chad Garner, PhD ImmunityBio, Inc.
PRS Account ImmunityBio, Inc.
Verification Date March 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP