Safety and Efficacy Study of ALT-801 to Treat Progressive Metastatic Malignancies
Condition: Progressive Metastatic Malignancies
MeSH terms: Neoplasms
Intervention: ALT-801
Intervention description: 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.
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
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

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.
    

Eligibility criteria:

        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