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

NCT01625260 | Terminated Phase 1 Results DMC

• 1 other identifier: CA-ALT-801-01-12
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Non-muscle Invasive Bladder Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (4)

• Duration of Response

  From confirmed complete response to up to 3 years

• Progression-free Survival

  From start of study treatment to up to 3 years

• Event-free Survival

  From start of study treatment to up to 3 years

• Overall Survival

  From start of study treatment to up to 3 years

Study Arms (2)

0.06 mg/kg ALT-801 with 1000 mg/m^2 Gemcitabine

EXPERIMENTAL

ALT-801 at 0.06 mg/kg with Gemcitabine at 1000 mg/m\^2

Biological: ALT-801; Drug: Gemcitabine

0.08 mg/kg ALT-801 with 1000 mg/m^2 Gemcitabine

EXPERIMENTAL

ALT-801 at 0.08 mg/kg with Gemcitabine at 1000 mg/m\^2

Biological: ALT-801; Drug: Gemcitabine

Interventions

ALT-801 BIOLOGICAL

Intravenous infusion: 2 treatment courses and 1 maintenance course; on Day 3, 5, 8 and 15 of each course.

Also known as: c264scTCR-IL2

0.06 mg/kg ALT-801 with 1000 mg/m^2 Gemcitabine; 0.08 mg/kg ALT-801 with 1000 mg/m^2 Gemcitabine

Gemcitabine DRUG

Intravenous infusion: 2 treatment courses and 1 maintenance course; on Day 1 and 8 of each course.

0.06 mg/kg ALT-801 with 1000 mg/m^2 Gemcitabine; 0.08 mg/kg ALT-801 with 1000 mg/m^2 Gemcitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Altor BioScience: lead
• James and Esther King Biomedical Research Program: collaborator

Study Sites (5)

University of Alabama Comprehensive Cancer Center

Birmingham, Alabama, 35294, United States

Location

University of California Davis

Sacramento, California, 95817, United States

Location

UF Health Center at Orlando Health

Orlando, Florida, 32806, United States

Location

University of Oklahoma Health Science Center

Oklahoma City, Oklahoma, 73104, United States

Location

UPMC Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Non-Muscle Invasive Bladder Neoplasms; Neoplasms; Urinary Bladder Neoplasms; Recurrence; Carcinoma in Situ; Carcinoma, Transitional Cell

Interventions

ALT-801; Gemcitabine

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Limitations and Caveats

Gemcitabine dosing was added in version 3 of the study protocol. 2 subjects were enrolled in protocol versions 1 and 2, which is why these subjects did not receive gemcitabine. The study was terminated early due to low enrollment.

Results Point of Contact

• Title: Sandeep Bobby Reddy, Chief Medical Officer
• Organization: ImmunityBio

Bobby.Reddy@Immunitybio.com

855-797-9277

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 19, 2012
• First Posted: June 21, 2012
• Study Start: March 30, 2012
• Primary Completion: March 8, 2018
• Study Completion: March 8, 2018
• Last Updated: July 19, 2024
• Results First Posted: July 19, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)