Safety and Efficacy Study of ALT-801 to Treat Progressive Metastatic Malignancies

NCT00496860 | Completed Phase 1 Results DMC

• 1 other identifier: CA-ALT-801-01-06
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase 1, open-labeled, non-randomized, multi-center, competitive enrollment and dose-escalation study of ALT-801, the study drug. The purpose of this study is to evaluate the safety, determine the maximum-tolerated dose (MTD) and characterize the pharmacokinetic profile of ALT-801 in previously treated patients with progressive metastatic malignancies. ALT-801, a recombinant fusion protein with a interleukin-2 (IL-2) component, has a targeting mechanism that recognizes tumor cells with a specific tumor marker.

Conditions

Progressive Metastatic Malignancies

Keywords

cancer; p53; immunotherapy; targeted; metastatic; malignancy; malignancies; interleukin-2; IL-2; fusion protein; antitumor; melanoma; renal cancer; lung cancer; kidney cancer; breast cancer; colorectal cancer; colon cancer; renal cell carcinoma; advanced cancer; head and neck cancer; breast tumors; cancer of head and neck; esophagus cancer; lymphoma; ovarian cancer; ovary cancer; bladder cancer; stomach cancer; TCR; T-cell receptor; P53 gene; p53 tumor suppressor protein

Outcome Measures

Primary Outcomes (2)

• The Safety and Toxicity of ALT-801 in Patients With Progressive Metastatic Malignancies

  Number of serious adverse events per cohort

  18 months

• The Maximum-tolerated Dose (MTD) of ALT-801

  Number of dose limiting toxicities (DLTs). A DLT is a toxicity that results in patient withdrawal from the study as defined in the protocol.

  18 months

Secondary Outcomes (3)

• Clinical Antitumor Response to ALT-801

  24 months

• ALT-801 Induced Cell-mediated Immune Responses

  24 months

• Immunogenicity of ALT-801

  24 months

Interventions

ALT-801 BIOLOGICAL

Dose escalation (0.015 mg/kg, 0.04 mg/kg, 0.08 mg/kg, 0.12 mg/kg, 0.14 mg/kg, 0.16 mg/kg), intravenous infusions, two treatment cycle, each cycle with 4 daily on-dose infusion, 10 days rest between cycles.

Eligibility Criteria

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

ENTRY CRITERIA: DISEASE CHARACTERISTICS: * Locally advanced or metastatic malignancies * Histologically or cytologically confirmed * Evaluable * Surgically and medically incurable * Not responding to standard therapy or no other standard therapy exists * Human leukocyte antigen (HLA)-A2.1/p53 positive PRIOR/CONCURRENT THERAPY: * No prior Proleukin therapy within one year * No concurrent radiotherapy, chemotherapy, or other immunotherapy * More than 4 weeks since prior major radiotherapy * More than 4 weeks since prior cytotoxic therapy * More than 6 weeks since prior nitrosoureas therapy * More than 8 weeks since prior monoclonal antibody therapy PATIENT CHARACTERISTICS: Life expectancy * \> 3 months Performance status * Eastern Cooperative Oncology Group (ECOG) Performance Status 0 or 1 Bone marrow reserve * Absolute neutrophil count (AGC/ANC) ≥ 1,500/microliters (uL) * Platelets ≥100,000/uL * Hemoglobin ≥ 10g/dL Renal function * Serum creatinine ≤ 1.5 X Upper limit of normal (ULN) Hepatic function * Total bilirubin ≤ 1.5 X ULN * Aspartate Aminotransferase (AST) ≤ 2.5 X ULN * Alkaline phosphatase ≤ 2.5 X ULN * Prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 X ULN * Activated partial thromboplastin time (aPTT) ≤ 1.5 X ULN Cardiovascular * May be safely tapered off anti-hypertensives if currently on anti-hypertensives * New York Heart Association classification I or II * No congestive heart failure \<6 months * No unstable angina pectoris \<6 months * No myocardial infarction \<6 months * No history of ventricular arrhythmias * Normal cardiac stress test required if any of the following is present: * Over age 50 * History of abnormal EKG * Symptoms of cardiac ischemia or arrhythmia Pulmonary * Normal pulmonary function test (FEV1 ≥ 75% of predicted value) if any of the following is present: * Prolonged history of cigarette smoking * Symptoms of respiratory dysfunction Other * No known autoimmune disease * No known HIV positive * No psychiatric illness/social situations that would limit study compliance * No history or evidence of central nervous system (CNS) disease * No active systemic infection requiring parental antibiotic therapy * No systemic steroid therapy required * No prior organ allograft * Not receiving other investigational agents * Not receiving chronic medication for asthma * Not pregnant or nursing * Fertile patients must use effective contraception

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

Sponsors & Collaborators

• Altor BioScience: lead

Study Sites (4)

University of Colorado, Anschutz Cancer Pavillion

Aurora, Colorado, 80045, United States

Location

MD Anderson Cancer Center Orlando

Orlando, Florida, 32806, United States

Location

H. Lee Moffitt Cancer Center & Research Institute

Tampa, Florida, 33612, United States

Location

University of Washington, Seattle Cancer Care Center

Seattle, Washington, 98109, United States

Location

Related Publications (1)

• Fishman MN, Thompson JA, Pennock GK, Gonzalez R, Diez LM, Daud AI, Weber JS, Huang BY, Tang S, Rhode PR, Wong HC. Phase I trial of ALT-801, an interleukin-2/T-cell receptor fusion protein targeting p53 (aa264-272)/HLA-A*0201 complex, in patients with advanced malignancies. Clin Cancer Res. 2011 Dec 15;17(24):7765-75. doi: 10.1158/1078-0432.CCR-11-1817. Epub 2011 Oct 12.

  PMID: 21994418 DERIVED

Related Links

• Altor Bioscience Corporation, Miramar, Florida, US
• H. Lee Moffitt Cancer Center \& Research Institute, Tampa, Florida, US
• MD Anderson Cancer Center Orlando

MeSH Terms

Conditions

Neoplasms; Neoplasm Metastasis; Melanoma; Kidney Neoplasms; Lung Neoplasms; Breast Neoplasms; Colorectal Neoplasms; Colonic Neoplasms; Carcinoma, Renal Cell; Head and Neck Neoplasms; Esophageal Neoplasms; Lymphoma; Ovarian Neoplasms; Urinary Bladder Neoplasms; Stomach Neoplasms

Interventions

ALT-801

Condition Hierarchy (Ancestors)

Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Genital Neoplasms, Female; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Urinary Bladder Diseases; Stomach Diseases

Results Point of Contact

• Title: Hing C. Wong, Chief Clinical Officer
• Organization: Altor Bioscience

hingwong@altorbioscience.com

9544438600

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: July 3, 2007
• First Posted: July 4, 2007
• Study Start: May 1, 2007
• Primary Completion: October 1, 2009
• Study Completion: October 1, 2009
• Last Updated: July 22, 2013
• Results First Posted: July 15, 2013

Record last verified: 2013-07

Locations

US (4)