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A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803 in Patients With Advanced Solid Tumors

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ClinicalTrials.gov Identifier: NCT01946789
Recruitment Status : Active, not recruiting
First Posted : September 20, 2013
Last Update Posted : April 10, 2018
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Altor BioScience

Brief Summary:
The proposed clinical trial is a phase I, open-label, multi-center, dose-escalation study of ALT-803 in patients with surgically incurable advanced solid tumors: melanoma, renal cell, non-small cell lung and squamous cell head and neck cancer

Condition or disease Intervention/treatment Phase
Advanced Solid Tumors Biological: ALT-803 Phase 1

Detailed Description:
This trial will investigate the safety and immunogenicity, immunomodulatory properties, and clinical benefits of treatment with weekly doses of ALT-803 in patients with advanced solid tumors.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 26 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of the Clinical and Immunologic Effects of ALT-803, a Novel Recombinant IL-15 Complex in Patients With Advanced Solid Tumors: Melanoma, Renal Cell, Non-Small Cell Lung and Squamous Cell Head and Neck Cancer
Actual Study Start Date : May 2014
Actual Primary Completion Date : August 2017
Estimated Study Completion Date : July 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: ALT-803 Biological: ALT-803
Intravenous infusion for dose level 1-5; subcutaneous injection for dose level 5a-8; two 6-week treatment cycles: ALT-803 on Day 1, 8, 15, 22; stable or benefitting patients may receive up to two additional 6-week cycles




Primary Outcome Measures :
  1. Safety profile and effectiveness of escalating doses of ALT-803 [ Time Frame: 9 months ]
    Safety and effectiveness of ALT-803 on the peripheral blood white blood cell (WBC) and absolute lymphocyte (ALC) counts. Defined by the increase in the total number of peripheral lymphocytes during the first cycle. The safety endpoint is the MTD of ALT-803, defined as the dose level below that at which ≥2 of 6 patients experience a DLT. The efficacy endpoint is the OBD, defined as that which produces an ALC ≥25,000/µL and/or a total WBC ≥35,000/µL among 2/3 of patients. For safety, we have also defined an "exceeding OBD" as the occurrence of ALC ≥35,000/µL and/or WBC ≥50,000/µL.


Secondary Outcome Measures :
  1. To evaluate the effect of escalating doses of ALT-803 [ Time Frame: 24 months ]
    On the number and phenotype of peripheral blood mononuclear cells (PBMCs)by multiparameter blood flow, the level of immune response to autochthonous viral and tumor antigens by interferon gamma (IFN-γ) ELISPOT, immunogenicity and pharmacokinetics of ALT-803 assessed by ELISA and overall objective response rate (ORR) and response duration assessed by evidence of antitumor activity as defined by objective responses and the pharmacokinetic and pharmacodynamic profiles of ALT-803



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

ENTRY CRITERIA:

DISEASE CHARACTERISTICS:

  • Histological or cytological confirmed malignancy in the following disease groups: melanoma that is metastatic or unresectable, non-small cell lung carcinoma, renal cell carcinoma or squamous cell head and neck carcinoma, for which standard curative or palliative measures do not exist or are no longer effective.
  • Primary site may be cutaneous or unknown, but mucosal and ocular primaries are excluded.
  • Patients with non-small lung cancer must have had prior EGFR and ALK testing. Patients with sensitizing mutations in EGFR or ALK rearrangements should have been treated with prior targeted agents and have had progression or discontinued due to toxicity from these agents.
  • No patients with known brain metastases.

PRIOR/CONCURRENT THERAPY:

  • At least one prior therapy using an agent with the potential for prolonged remission.
  • Patients with BRAF v600 mutation should be excluded or may be included after experiencing progression following treatment with BRAF inhibitor regimen or if they consent to forgo FDA-approved therapies that increase median survival.
  • At least 4 weeks from last dose of prior chemotherapy or immunomodulator therapy with full recovery of acute toxicities. For patients coming off molecularly-targeted therapy, at least 2 weeks since last dose and recovery from laboratory and constitutional toxicities.
  • At least 2 weeks from completion of prior radiation therapy with full recovery from toxicities.
  • At least 4 weeks from last dose of prior investigational therapy with recovery to meet baseline eligibility criteria.
  • Not receiving any current anticancer therapy
  • No patients who have had chemotherapy, targeted therapy, or radiotherapy and have not recovered from acute toxicity to their pretreatment baseline or to a grade 1 level within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study. For resolution of autoimmune toxicity from prior immune therapy, patients must be off steroids for at least 30 days without relapse of autoimmune toxicity, or it must be at least 30 days from their last dose of infliximab or related immunosuppressive therapy without relapse of autoimmune toxicity.
  • No patients who are receiving any other investigational agents.
  • No patients who are receiving chronic systemic or regular inhaled corticosteroid use within 7 days prior to initiation of protocol therapy.
  • No immunosuppressive therapy within 30 days prior to treatment start.

PATIENT CHARACTERISTICS

  • Age >18 years
  • Both men and women of all races and ethnic groups are eligible.

Performance Status

  • ECOG performance status ≤1
  • Life expectancy of greater than 6 months.

Bone Marrow Function

  • leukocytes ≥3,000/mcL
  • absolute lymphocyte count ≥500/mcL
  • absolute neutrophil count ≥1,000/mcL (without hematopoietic growth factors)
  • platelets ≥100,000/mcL (without transfusion)
  • hemoglobin ≥ 10 gm/dL (may be transfused but must be stable without clinical evidence of ongoing blood loss or hemolysis)

Hepatic Function

  • total bilirubin within normal institutional limits
  • AST(SGOT)/ALT(SGPT) ≤2.5 × institutional upper limit of normal

Kidney Function

  • Creatinine within normal institutional limits OR
  • Creatinine clearance ≥60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal.

Pulmonary Function

• No history of severe COPD or emphysema or interstitial lung disease currently on home supplemental oxygen. Patients with NSCLC with stable COPD or emphysema not requiring supplemental oxygen are eligible.

Cardiac Function

  • No symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia. Patients who have underlying risk factors for cardiac disease should be excluded or undergo clearance stress-based cardiac function testing. The pre-treatment QTc must be <500 msec.
  • No class II or greater congestive heart failure as described in the New York Heart Association Functional Classification criteria or serious arrhythmias likely to increase the risk of cardiac complications of cytokine therapy.

Other

  • Women of child-bearing potential and men must agree to use adequate contraception.
  • Ability to understand and the willingness to sign a written informed consent document.
  • No uncontrolled inter-current illness or psychiatric illness/social situations that would limit compliance with study requirements.
  • No pregnant women.
  • No HIV-positive patients.
  • No positive hepatitis C serology or active hepatitis B infection.
  • No active bacterial or fungal infection.
  • No inability to home monitor blood pressure.
  • Patients with thyroid disease should be excluded unless euthyroid on suppressive or replacement therapy.

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 ClinicalTrials.gov identifier (NCT number): NCT01946789


Locations
United States, Maryland
National Institutes of Health
Bethesda, Maryland, United States, 20892
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, New Hampshire
Dartmouth Hitchcock Medical Center
Lebanon, New Hampshire, United States, 03756
United States, New Jersey
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States, 08901
United States, Ohio
Cleveland Clinic Foundation
Cleveland, Ohio, United States, 44195
United States, Washington
University of Washington, Seattle Cancer Care Alliance
Seattle, Washington, United States, 98109
Sponsors and Collaborators
Altor BioScience
National Cancer Institute (NCI)
Investigators
Principal Investigator: Marc Ernstoff, MD Roswell Park Cancer Institute

Responsible Party: Altor BioScience
ClinicalTrials.gov Identifier: NCT01946789     History of Changes
Other Study ID Numbers: CITN06-ALT-803
U01CA154967 ( U.S. NIH Grant/Contract )
First Posted: September 20, 2013    Key Record Dates
Last Update Posted: April 10, 2018
Last Verified: April 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Altor BioScience:
cancer
IL-15
melanoma
metastatic
unresectable
solid tumors
renal cell
non-small cell lung
squamous cell head and neck