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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

Tracking Information
First Submitted Date  ICMJE July 3, 2007
First Posted Date  ICMJE July 4, 2007
Results First Submitted Date  ICMJE April 2, 2013
Results First Posted Date  ICMJE July 15, 2013
Last Update Posted Date July 22, 2013
Study Start Date  ICMJE May 2007
Actual Primary Completion Date October 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 10, 2013)
  • The Safety and Toxicity of ALT-801 in Patients With Progressive Metastatic Malignancies [ Time Frame: 18 months ]
    Number of serious adverse events per cohort
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 3, 2007)
  • To evaluate the safety and toxicity of ALT-801 in patients with progressive metastatic malignancies.
  • To determine the maximum-tolerated dose (MTD) of ALT-801.
  • To characterize the pharmacokinetics of ALT-801.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 10, 2013)
  • 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.
  • 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
  • Immunogenicity of ALT-801 [ Time Frame: 24 months ]
    Titer of anti-drug Abs at week 4
Original Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2007)
  • To assess clinical antitumor response to ALT-801.
  • To evaluate ALT-801 induced cell-mediated immune responses.
  • To evaluate immunogenicity of ALT-801.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Safety and Efficacy Study of ALT-801 to Treat Progressive Metastatic Malignancies
Official Title  ICMJE Phase I Study of ALT-801 in Patients With Progressive Metastatic Malignancies
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Progressive Metastatic Malignancies
Intervention  ICMJE 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.
Study Arms  ICMJE Not Provided
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 26, 2009)
Original Estimated Enrollment  ICMJE
 (submitted: July 3, 2007)
Actual Study Completion Date  ICMJE October 2009
Actual Primary Completion Date October 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE



  • 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
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 information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00496860
Other Study ID Numbers  ICMJE CA-ALT-801-01-06
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Altor BioScience
Study Sponsor  ICMJE Altor BioScience
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Altor BioScience
Verification Date July 2013

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