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Multi Tumor-Associated Antigen-Specific T Lymphocytes to Treat Patients With High Risk Solid Tumors

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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05238792
Recruitment Status : Recruiting
First Posted : February 14, 2022
Last Update Posted : October 26, 2022
Sponsor:
Information provided by (Responsible Party):
Amy Hont, Children's National Research Institute

Brief Summary:
This is a phase I dose-escalation study to evaluate the safety of partially human leukocyte antigen (HLA)-matched multi tumor-associated antigen-specific T cell (TAA-T) therapy for patients with high-risk solid tumors due to the presence of refractory, relapsed and/or minimal residual detectable disease following conventional therapy. Conventional therapy may include chemotherapy, surgery, radiation, autologous stem cell transplant, or targeted therapy.

Condition or disease Intervention/treatment Phase
Solid Tumor Biological: Tumor-associated antigen-specific T cell (TAA-T) Phase 1

Detailed Description:

In this dose escalation trial, three dose levels, with two arms dependent on age, will be tested for safety. Arm A will enroll patients age ≥18 years and <70 years and Arm B will enroll patients age ≥6 years and <18 years. TAA-T product will first be administered to patients as monotherapy at dose level 1 to determine safety. Following demonstration of safety in dose level 1, lymphodepleting chemotherapy will be administered prior to the first dose of TAA-Ts on the dose escalation phase (dose levels 2 and 3). The TAA-T product will be assessed for safety and anti-tumor activity.

Description of Study Intervention:

The treatment schedule is as follows: Patients will receive an infusion of partially HLA-matched TAA-T any time >1 week after completing most recent course of conventional (non-investigational) therapy for their disease. For the lymphodepletion cohort, patients will receive lymphodepletion (LD) chemotherapy >2 weeks from most recent course of conventional therapy and will nadir and recover before beginning TAA-T therapy. Patients will be enrolled to one of the following TAA-T dose levels:

BSA <1.20 BSA ≥1.20 Dose level 1 without LD (low dose) 2x107 cells 4x107 cells Dose level 2 (LD + Low dose) 2x107 cells 4x107 cells Dose level 3 (LD + High dose) 4x107 cells 8x107 cells

There will be separate study arms for adult (Arm A) and pediatric (Arm B) patients:

Arm A Age ≥18 years and <70 years Arm B Age ≥6 years and <18 years Enrollment will first be restricted to Arm A on dose level 1 (DL1). Following demonstration of safety, enrollment will start on dose level 2 (DL2) on Arm A for an additional 3 patients and we will contact the U.S Food and Drug Administration (FDA) with the safety data from the first 3 adults treated on DL1 to initiate enrollment on Arm B. Following demonstration of safety on Arm A at DL2, we will open enrollment to all patients (Arm A and B). Three patients will be enrolled at each dose level until the maximum tolerated dose (MTD) is determined, at which point to ensure safety, a total of 6 patients will be treated at the MTD.

One additional dose of TAA-Ts can be administered without lymphodepleting chemotherapy from day 45 after the initial infusion if there is a partial response (based on response evaluation criteria in solid tumors (RECIST)) or no response with stable disease, or if the patient receives immunosuppressive therapy that would compromise TAA-T persistence after the first infusion (such as corticosteroids), and if the patient has not experienced dose-limiting toxicities related to the study product and meets eligibility criteria for the additional infusion. Each patient will receive at least one TAA-T infusion and may receive a maximum of 2 doses. The first and second doses will be administered a minimum of 45 days apart. The expected volume of each infusion is 1 to 10 cc, though may be greater in larger patients. Dose escalation will occur once at least 3 patients on each study arm have completed the 45 day follow up period following their first TAA-T infusion. Response will be monitored after the first infusion at day 45, then at day 28 after subsequent infusion if administered.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Research Study Utilizing Allogeneic Multi Tumor-Associated Antigen-Specific T Lymphocytes to Advance the Care of Patients With High-Risk Solid Tumors
Actual Study Start Date : November 17, 2021
Estimated Primary Completion Date : October 2025
Estimated Study Completion Date : October 2027

Arm Intervention/treatment
Experimental: Arm A for patients age ≥18 years and <70 years
Arm A will enroll patients age ≥18 years and <70 years. TAA-T product will first be administered to patients as monotherapy at dose level 1 to determine safety. Following demonstration of safety in dose level 1, lymphodepleting chemotherapy will be administered prior to the first dose of TAA-Ts on the dose escalation phase (dose levels 2 and 3). The TAA-T product will be assessed for safety and anti-tumor activity.
Biological: Tumor-associated antigen-specific T cell (TAA-T)

Patients will receive an infusion of partially HLA-matched TAA-T any time >1 week after completing most recent course of conventional (non-investigational) therapy for their disease. For the lymphodepletion cohort, patients will receive lymphodepletion (LD) chemotherapy >2 weeks from most recent course of conventional therapy and will nadir and recover before beginning TAA-T therapy. Patients will be enrolled to one of the following TAA-T dose levels:

BSA <1.20 BSA ≥1.20 Dose level 1 without LD (low dose) 2x107 cells 4x107 cells Dose level 2 (LD + Low dose) 2x107 cells 4x107 cells Dose level 3 (LD + High dose) 4x107 cells 8x107 cells


Experimental: Arm B for patients age ≥6 years and <18 years
Arm B will enroll patients age ≥6 years and <18 years. TAA-T product will first be administered to patients as monotherapy at dose level 1 to determine safety. Following demonstration of safety in dose level 1, lymphodepleting chemotherapy will be administered prior to the first dose of TAA-Ts on the dose escalation phase (dose levels 2 and 3). The TAA-T product will be assessed for safety and anti-tumor activity.
Biological: Tumor-associated antigen-specific T cell (TAA-T)

Patients will receive an infusion of partially HLA-matched TAA-T any time >1 week after completing most recent course of conventional (non-investigational) therapy for their disease. For the lymphodepletion cohort, patients will receive lymphodepletion (LD) chemotherapy >2 weeks from most recent course of conventional therapy and will nadir and recover before beginning TAA-T therapy. Patients will be enrolled to one of the following TAA-T dose levels:

BSA <1.20 BSA ≥1.20 Dose level 1 without LD (low dose) 2x107 cells 4x107 cells Dose level 2 (LD + Low dose) 2x107 cells 4x107 cells Dose level 3 (LD + High dose) 4x107 cells 8x107 cells





Primary Outcome Measures :
  1. The rate of toxicities after TAA-T infusion [ Time Frame: 45 days ]
    • Incidence of grades 3 to 5 infusion-related adverse event occurring within 45 days of the first TAA-T infusion.
    • Incidence of grades 4 to 5 non-hematologic adverse event related to TAA-T product occurring within 45 days of the first TAA-T infusion and that are not due to the patient's underlying malignancy or pre-existing co-morbidities.
    • Incidence of grades 3 to 4 acute GVHD occurring within 45 days of the first TAA-T infusion.
    • Incidence of unexpected toxicities of any grade attributed to the infusion of TAA-T occurring within 45 days of the first TAA-T dose.


Secondary Outcome Measures :
  1. Anti-tumor activity based on tumor response [ Time Frame: 1 year ]
    Determine the number of patients who respond to TAA-T cells



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:   6 Years to 70 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

PARTICIPANT INCLUSION CRITERIA

RECIPIENT SCREENING INCLUSION CRITERIA

  • Diagnosis of high-risk solid tumors known to express at least 2 targeted antigens by either histology or historical reference: Ewing sarcoma, Wilms tumor, neuroblastoma, rhabdomyosarcoma, soft tissue sarcoma, and osteosarcoma.
  • HLA type and match through at least one allele with antigen-specific activity.
  • Refractory disease, residual detectable disease following conventional therapy or relapsed disease.
  • Arm A: age ≥18 years and <70 years
  • Arm B: age ≥6 years to <18 years
  • Patient or parent/guardian capable of providing informed consent.

RECIPIENT INCLUSION CRITERIA FOR INITIAL TAA-T ADMINISTRATION AND FOR SUBSEQUENT INFUSION

  • No systemic steroid exposure within 1 week of TAA-T infusion.
  • Karnofsky/Lansky score of ≥50% (see Appendix 4).
  • Left ventricular ejection fraction (LVEF) >50% or left ventricular systolic dysfunction (LVSD) >27% if history of total body irradiation (TBI) (may be performed within the last 6 months).
  • Hemoglobin >7.0 g/dL (level can be achieved with transfusion).
  • Bilirubin ≤2.5 mg/dL.
  • Aspartate transaminase (AST)/Alanine transaminase (ALT) ≤5 x the upper limit of normal for age.
  • Serum creatinine <1.0 mg/dL or 2x the upper limit of normal for age (whichever is higher).
  • Pulse oximetry of >90% on room air.
  • Negative pregnancy test in female patient of childbearing age.
  • Agree to use contraceptive measures during study protocol participation (when age appropriate).
  • Patients receiving lymphodepleting chemotherapy must have:

    • Absolute neutrophil count (ANC) >1000 /ul.
    • Platelet count >75,000 /ul.

Exclusion Criteria:

PARTICIPANT EXCLUSION CRITERIA RECIPIENT SCREENING EXCLUSION CRITERIA

  • Patients with known human immunodeficiency virus (HIV) infection.
  • Pregnant or lactating females.
  • Patients who have undergone previous allogeneic stem cell transplant.
  • Patients who have undergone previous autologous stem cell transplant within the past 60 days.

RECIPIENT EXCLUSION CRITERIA FOR INITIAL AND SUBSEQUENT TAA-T INFUSION

  • Patients with uncontrolled infections. Uncontrolled infections are defined as bacterial, fungal, or viral infections with either clinical signs of worsening despite standard therapy. Progressing infection is defined as hemodynamic instability, worsening physical signs, or radiographic findings attributable to infection. Persisting fever without other signs or symptoms will not be interpreted as progressing infection.

    • For bacterial infections, patients must be receiving definitive therapy and have no signs of progressing infection within 7 days prior to TAA-T infusion.
    • For fungal infections, patients must be receiving definitive systemic anti-fungal therapy and have no signs of progressing infection within 7 days prior to TAA-T infusion.
  • Patients who received ATG, Campath or other immunosuppressive T cell monoclonal antibodies within 28 days prior to TAA-T infusion.
  • For patients receiving lymphodepleting chemotherapy: exposure to chemotherapy or immunomodulatory medications within the last 2 weeks prior to treatment.
  • Pregnant or lactating females.

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): NCT05238792


Contacts
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Contact: Amy Hont, MD 202-476-3887 ahoughte@childrensnational.org
Contact: Fahmida Hoq, MBBS 202-476-3634 fhoq@childrensnational.org

Locations
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United States, District of Columbia
Children's National Hospital Recruiting
Washington, District of Columbia, United States, 20010
Contact: Amy Hont, MBBS, MS    202-476-3887    ahoughte@childrensnational.org   
Principal Investigator: Amy Hont, MD         
Sponsors and Collaborators
Children's National Research Institute
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Responsible Party: Amy Hont, Oncologist, Children's National Research Institute
ClinicalTrials.gov Identifier: NCT05238792    
Other Study ID Numbers: ATTACK
First Posted: February 14, 2022    Key Record Dates
Last Update Posted: October 26, 2022
Last Verified: October 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Neoplasms