A Study of ALT-801 in Combination With Cisplatin and Gemcitabine in Muscle Invasive or Metastatic Urothelial Cancer

NCT01326871 | Completed Phase 1 Results DMC

• 1 other identifier: CA-ALT-801-01-10
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 16

Brief Summary

This is a Phase Ib/II, open-label, multi-center, competitive enrollment and dose-escalation study of ALT-801 in a biochemotherapy regimen either containing cisplatin and gemcitabine or containing gemcitabine alone in patients who have muscle invasive or metastatic urothelial cancer of bladder, renal pelvis, ureters and urethra. The purpose of this study is to evaluate the safety, determine the maximum tolerated dose (MTD) and the recommended dose (RD), and assess the anti-tumor response of ALT-801 in combination with cisplatin and gemcitabine or ALT-801 in combination with gemcitabine alone. The pharmacokinetic profile of ALT-801 in combination with cisplatin and gemcitabine will also be assessed. The study includes a dose escalation phase (Phase Ib) and a dose expansion phase (Phase II). Phase II has two treatment groups, Expansion Group 1 and Expansion Group 2. Expansion Group 2 is for platinum-refractory patients, consisting of two treatment arms based on the patient's renal function. Patients will enroll to Expansion Group 2 after stage 1 of the Group 1 expansion is complete.

Conditions

Transitional Cell Carcinoma of Bladder; Urethra Cancer; Ureter Cancer; Malignant Tumor of Renal Pelvis

Keywords

cancer; immunotherapy; immunochemotherapy; combinational therapy; targeted; metastatic; muscle invasive; interleukin-2; cisplatin; gemcitabine; antitumor; TCR; T-cell receptor; p53; p53 gene; p53 tumor supressor protein; urothelial cancer; bladder cancer; renal pelvis cancer; ureters cancer; urethra cancer; HLA-A2 positive; HLA-A*0201/p53 aa264-272; HLA complex; Muscle Invasive or Metastatic

Outcome Measures

Primary Outcomes (3)

• Maximum Tolerated Dose (MTD) and/or the Recommended Dose (RD) for Dose Expansion of ALT-801 in Combination With Cisplatin and Gemcitabine or ALT-801 in Combination With Gemcitabine Alone

  8 weeks

• Number of Participants With Adverse Events

  Number of AEs that occur or worsen after the first dose of study treatment

  8 weeks

• Objective Response Rate in Treated Patients

  Objective response rate (ORR) is defined as confirmed complete response (CR) or partial response (PR) using Response Evaluation Criteria in Solid Tumors \[RECIST V1.0\]: a complete response is the disappearance of all target lesions; a partial response is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. ORR = CR + PR.

  12 weeks

Study Arms (3)

ALT-801 0.04 mg/kg with Cisplatin and Gemcitabine

EXPERIMENTAL

Drug: Cisplatin; Drug: Gemcitabine; Biological: ALT-801

ALT-801 0.06 mg/kg with Cisplatin and Gemcitabine

EXPERIMENTAL

Drug: Cisplatin; Drug: Gemcitabine; Biological: ALT-801

ALT-801 0.06 mg/kg with Gemcitabine

EXPERIMENTAL

Drug: Gemcitabine; Biological: ALT-801

Interventions

Cisplatin DRUG

Intravenous infusion; 3 initial treatment courses and an additional 3 maintenance courses for responders (maintenance revised for Phase II): on day 1 of each course (if given)

ALT-801 0.04 mg/kg with Cisplatin and Gemcitabine; ALT-801 0.06 mg/kg with Cisplatin and Gemcitabine

Gemcitabine DRUG

Intravenous infusion; 3 initial treatment courses and an additional 3 maintenance courses for responders (maintenance revised for Phase II); on day 1 and 8 of each course

ALT-801 0.04 mg/kg with Cisplatin and Gemcitabine; ALT-801 0.06 mg/kg with Cisplatin and Gemcitabine; ALT-801 0.06 mg/kg with Gemcitabine

ALT-801 BIOLOGICAL

Intravenous infusion; 3 initial treatment courses and an additional 3 maintenance courses for responders (maintenance revised for Phase II): on day 3, 5, 8, and 12 of each course

Also known as: c264scTCR-IL2

ALT-801 0.04 mg/kg with Cisplatin and Gemcitabine; ALT-801 0.06 mg/kg with Cisplatin and Gemcitabine; ALT-801 0.06 mg/kg with Gemcitabine

Eligibility Criteria

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

ENTRY CRITERIA: DISEASE CHARATERISTICS: * Muscle invasive or metastatic urothelial cancer of bladder, ureters, renal pelvis, and urethra * Histologically or cytologically confirmed with a clinical plan that would potentially include cisplatin\* plus gemcitabine systemic therapy or with disease refractory to a first-line platinum-based therapy (as defined in the protocol). \* Does not apply to patients screened for Phase II expansion * Surgically incurable PRIOR/CONCURRENT THERAPY: * No concurrent radiotherapy, other chemotherapy, or other immunotherapy * Must have recovered from side effects of prior treatments * If prior Proleukin® treatment, must have had a clinical benefit * No use of other investigational agents within 30 days of start or concurrently PATIENT CHARACTERISTICS: Age * ≥ 18 years Performance Status * ECOG 0 or 1 Bone Marrow Reserve * Absolute neutrophil count (AGC/ANC) ≥ 1,500/uL * Platelets ≥ 100,000/uL * Hemoglobin ≥ 10g/dL Renal Function * Glomerular Filtration Rate (GFR): * ≥ 50mL/min/1.73m\^2 for cisplatin-containing regimen * ≥ 40mL/min/1.73m\^2 for non-cisplatin-containing regimen Hepatic Function * Total bilirubin ≤ 1.5 X ULN * AST, ALT, ALP ≤ 2.5 X ULN, or ≤ 5.0 X ULN (if liver metastases exists) * PT INR ≤ 1.5 X ULN Cardiovascular * No congestive heart failure \< 6 months * No unstable angina pectoris \< 6 months * No myocardial infarction \< 6 months * No history of ventricular arrhythmias * No NYHA Class \> II CHF * Normal cardiac stress test required for subjects who are ≥ 50 years old, or have a history of EKG abnormalities, or have symptoms of cardiac ischemia or arrhythmia * No uncontrolled hypertension Pulmonary * Not receiving chronic medication for asthma * Normal clinical assessment of pulmonary function Hematologic * No evidence of bleeding diathesis or coagulopathy Other * Negative serum pregnancy test if female and of childbearing potential * No women who are 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 CNS disease (Controlled brain metastases treated with radiation therapy or surgery where the disease has been clinically stable for a period of a least 3 months before screening is allowed) * 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
• National Cancer Institute (NCI): collaborator

Study Sites (16)

The University of Arizona Cancer Center

Tucson, Arizona, 85724, United States

Location

UF Health Center at Orlando Health

Orlando, Florida, 32806, United States

Location

Martin Health System

Stuart, Florida, 34994, United States

Location

H. Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33612, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Robert Lurie Comprehensive Cancer Center of Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Cancer Center

Fairway, Kansas, 66205, United States

Location

Karmanos Cancer Center

Detroit, Michigan, 48201, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

Location

University of Oklahoma Health Science Center

Oklahoma City, Oklahoma, 73104, United States

Location

St. Luke's Hospital and Health Network

Easton, Pennsylvania, 18045, United States

Location

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

MeSH Terms

Conditions

Urethral Neoplasms; Ureteral Neoplasms; Neoplasms; Neoplasm Metastasis; Urinary Bladder Neoplasms

Interventions

Cisplatin; Gemcitabine; ALT-801

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urethral Diseases; Urologic Diseases; Male Urogenital Diseases; Ureteral Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Urinary Bladder Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

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: March 30, 2011
• First Posted: March 31, 2011
• Study Start: September 6, 2011
• Primary Completion: April 11, 2016
• Study Completion: April 11, 2016
• Last Updated: June 25, 2024
• Results First Posted: May 14, 2024

Record last verified: 2024-06

Locations

US (16)