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

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. Read our disclaimer for details. Identifier: NCT00496860
Recruitment Status : Completed
First Posted : July 4, 2007
Results First Posted : July 15, 2013
Last Update Posted : July 22, 2013
Information provided by (Responsible Party):
Altor BioScience

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.

Condition or disease Intervention/treatment Phase
Progressive Metastatic Malignancies Biological: ALT-801 Phase 1

Detailed Description:

Most current cancer treatment strategies involve the use of chemotherapeutic or biological drugs that exhibit variable efficacy and considerable toxicity. The limitations are often the result of the adverse side effects of the therapeutic drug on normal tissues. One approach to control these effects is to target the therapy to the tumor site. Of the identified tumor antigens, the human p53 tumor suppressor protein is overexpressed in a wide range of human malignancies. p53 is an intracellular tumor suppressor protein that acts to arrest the proliferation of cells. When mutated, it loses its ability to suppress abnormal proliferation and exhibits a longer half-life than the wild-type protein, allowing for its accumulation in tumors. In addition, p53 overexpression correlates with tumor transformation and aggression and is associated with lower overall survival rates and resistance to chemotherapeutic intervention in cancer patients. Therefore, p53 appears to be a marker for a considerable number of human malignancies and represents a good target for immunotherapeutics. However, p53 cannot be used as a target for antibodies because it is not displayed independently on the cell surface. Instead, the p53 protein is processed intracellularly into peptide fragments that are then displayed on the cell surface in the context of major histocompatibility complex (MHC). These peptide/MHC complexes are recognized by T-cells via their T-cell receptors (TCRs). Recently it has been confirmed that the peptide fragment is significantly elevated in a wide range of human tumor tissues, particularly in melanoma, renal, lung, breast, colorectal, bladder, ovary, stomach, esophagus, lymphoma, liver, leukemia, and head & neck cancer. Targeted approaches to concentrate therapeutic cytokines at the tumor sites that express p53 could provide considerable advantages over current treatment.

Interleukin-2 (IL-2) is a well-characterized growth factor for immune effector cells which play critical roles in tumor control and rejection. A recombinant human IL-2 has been approved for treating metastatic melanoma and renal cell carcinoma. However, the major drawback of IL-2 therapy is its severe systemic toxicity. As a result, use of high dose IL-2 is limited to specialized programs with experienced personnel and it is generally offered to patients who are responsive and have excellent organ function. Thus, there is a critical need for innovative strategies that enhance the effects of IL-2 or reduce its toxicity without compromising clinical benefits.

The study drug, ALT-801, is a biologic compound composed of interleukin-2 (IL-2) genetically fused to a humanized soluble T-cell receptor directed against the p53-derived antigen. This study is to evaluate whether directing IL-2 activity using ALT-801 to the patient's tumor sites that overexpress p53 results in clinical benefits.

The study drug will be administered by bolus intravenous infusion in an in-patient hospital setting under the supervision of a qualified physician experienced in the use of anti-cancer agents including high dose IL-2. An intensive care facility and specialists skilled in cardiopulmonary or intensive care medicine must be available. There are two treatment cycles. For each treatment cycle, patients will be admitted to the hospital, remain in the hospital during the study drug infusion period, and be discharged from the hospital the day after the last infusion at the Principal Investigator's discretion. There is a 10-day resting period between the treatment cycles. Tumor assessments will be done at weeks 7 and 11 after starting the study drug.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of ALT-801 in Patients With Progressive Metastatic Malignancies
Study Start Date : May 2007
Actual Primary Completion Date : October 2009
Actual Study Completion Date : October 2009

Intervention Details:
  • Biological: ALT-801
    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.

Primary Outcome Measures :
  1. The Safety and Toxicity of ALT-801 in Patients With Progressive Metastatic Malignancies [ Time Frame: 18 months ]
    Number of serious adverse events per cohort

  2. The Maximum-tolerated Dose (MTD) of ALT-801 [ Time Frame: 18 months ]
    Number of dose limiting toxicities (DLTs). A DLT is a toxicity that results in patient withdrawal from the study as defined in the protocol.

Secondary Outcome Measures :
  1. Clinical Antitumor Response to ALT-801 [ Time Frame: 24 months ]
    Number of subjects with a complete response (CR), partial response (PR) or stable disease (SD). CR is defined as disappearance of all tumor lesions selected for measurement. PR is defined as at least 30% decrease in the sum of all tumor lesions selected for measurement. Stable disease is defined as neither sufficient tumor shrinkage to qualify for PR nor sufficient tumor increase to qualify for progressive disease (PD) which is defined as at least 20% increase the sum of the all tumor lesions selected for measurement.

  2. ALT-801 Induced Cell-mediated Immune Responses [ Time Frame: 24 months ]
    Number of tumor-responsive (interferon-gamma positive (IFNg+)) immune cells in blood post dosing

  3. Immunogenicity of ALT-801 [ Time Frame: 24 months ]
    Titer of anti-drug Abs at week 4

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No



  • 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


  • 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


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


  • 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


  • 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


  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00496860

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United States, Colorado
University of Colorado, Anschutz Cancer Pavillion
Aurora, Colorado, United States, 80045
United States, Florida
MD Anderson Cancer Center Orlando
Orlando, Florida, United States, 32806
H. Lee Moffitt Cancer Center & Research Institute
Tampa, Florida, United States, 33612
United States, Washington
University of Washington, Seattle Cancer Care Center
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Altor BioScience
Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Altor BioScience Identifier: NCT00496860    
Other Study ID Numbers: CA-ALT-801-01-06
First Posted: July 4, 2007    Key Record Dates
Results First Posted: July 15, 2013
Last Update Posted: July 22, 2013
Last Verified: July 2013
Keywords provided by Altor BioScience:
fusion protein
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
ovarian cancer
ovary cancer
bladder cancer
stomach cancer
Additional relevant MeSH terms:
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