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Anti-NY-ESO-1 TCR-Gene Engineered Lymphocytes Given by Infusion to Patients With NY-ESO-1 -Expressing Metastatic Cancers

Primary Purpose

Sarcoma, Synovial, Sarcoma,Soft Tissue, Melanoma Stage IV

Status
Recruiting
Phase
Phase 1
Locations
Israel
Study Type
Interventional
Intervention
CYCLOPHOSPHAMIDE and FLUDARABIN
Cyclophosphamide
HBI 0201-ESO TCRT
Aldesleukin
Sponsored by
Hadassah Medical Organization
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sarcoma, Synovial focused on measuring NY-ESO-1, TCR, adoptive transfer, retroviral transduction

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Have histologically or cytologically confirmed diagnosis of neoplasia
  2. Measurable (per RECIST v1.1 criteria) metastatic cancer or locally advanced refractory/recurrent malignancy not amenable to curative treatment. Lesions previously irradiated may be considered measurable only if growth has been documented since local treatment completion.
  3. The tumor expresses ESO as assessed immunohistochemistry of resected tissue. To this end, archived tumor tissue suitable for analysis must be available or re-biopsy performed on study. Tissue staining must encompass more than 10% of tumor section.
  4. Patients must have previously either (1) received at least first-line or second-line standard therapy for metastatic disease, if known to be effective for that disease, and have been either non-responders (progressive disease), intolerable or have recurred or (2) Recurred within 6 months of adjuvant systemic therapy known to be active also in the metastatic setting.
  5. Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible.
  6. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo).
  7. Age ≥ 18 years and ≤ 70 years.
  8. Patient is able to understand and willing to sign a written informed consent.
  9. Clinical performance status of ECOG 0, 1 or 2.
  10. HLA-A*0201or A*0206 positive.
  11. Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after treatment.
  12. Women of child-bearing potential must have a negative pregnancy test.
  13. Serology: Seronegative for HIV antibody, hepatitis B antigen, and hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative.
  14. Hematology

    • ANC > 1500/mm3 without the support of filgrastim
    • WBC ≥ 3000/mm3
    • Platelet count ≥ 100,000/mm3
    • Hemoglobin > 8.0 g/dL. Subjects may be transfused to reach this cut-off.
  15. Chemistry

    • Serum ALT/AST ≤ 2.5 x ULN
    • Creatinine clearance ≥40ml/min
    • Total bilirubin ≤ 1.5 mg/dL, except in patients with Gilbert's Syndrome, who must have a total bilirubin < 3.0 mg/dL.
    • INR < 1.5

Exclusion Criteria:

  1. Women of child-bearing potential who are pregnant or breastfeeding.
  2. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease).
  3. Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses
  4. Concurrent systemic steroid therapy, not including replacement therapy or treatment with prednisone up to 10mg daily or its equivalent. Or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention.
  5. History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin.
  6. Subjects with a history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within 3 months.
  7. Subjects unable to maintain normal oxygen saturation level in room air.
  8. Subjects who have had a venous thromboembolic event requiring anticoagulation and who meet any of the following criteria:

    • Have been on a stable dose of anticoagulation for < 1 month (except for acute line insertion induced thrombosis).
    • Have had a Grade 2, 3, or 4 hemorrhage in the last 30 days or are experiencing continued symptoms from their venous thromboembolic event (e.g. continued dyspnea or oxygen requirement).
  9. Has a known additional malignancy within the last 3 years. Exceptions include early stage cancers (carcinoma in situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy).
  10. LVEF ≤ 40%
  11. Documented FEV1 ≤ 60% predicted tested in patients with:

    • A prolonged history of cigarette smoking (≥ 20 pack-year smoking history, with cessation within the past two years).
    • Symptoms of respiratory dysfunction.
  12. Patients who are at the time of study initiation receiving any other investigational agents.
  13. Carcinomatosis meningitis or other brain involvement exceeding that allowed above.
  14. Has received live vaccine within 30 days before the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.

Sites / Locations

  • Hadassah Medical OrganizationRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

HBI 0201-ESO TCRT (Anti-NY-ESO-1 TCR-transduced peripheral blood lymphocytes)

Arm Description

This is a two-part, non-randomized, open label, single-site Phase I/II study. The first Part A is a dose ranging maximum tolerated dose (MTD) study and Part B is an extension phase to evaluate safety at the selected safe dose. A Data Safety Monitoring Board (DSMB) will determine the safe dose for testing in the expansion phase (Part B). Part A will be according to a 3+3 dose escalation design. A total of up to 20 patients will participate in this Part. Part B will be an expansion phase. The objective will be to determine if the treatment regimen is associated with a clinical response rate that can rule out 5% (p0=0.05) in favor of a modest 20% Partial Response (PR) + Complete Response (CR) rate (p1=0.20). A total of up to 43 patients may be enrolled in Part B (41 +2, allowing for up to 2 non-evaluable patients).

Outcomes

Primary Outcome Measures

Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Adverse events that occur following engineered T cell transfer
objective tumor regression
change in index lesions' size

Secondary Outcome Measures

immune monitoring for transferred cells persistence
blood test for ESO-TCRT cells' presence

Full Information

First Posted
February 22, 2022
Last Updated
September 21, 2023
Sponsor
Hadassah Medical Organization
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1. Study Identification

Unique Protocol Identification Number
NCT05296564
Brief Title
Anti-NY-ESO-1 TCR-Gene Engineered Lymphocytes Given by Infusion to Patients With NY-ESO-1 -Expressing Metastatic Cancers
Official Title
A Phase I/II Dose Escalation, Safety and Efficacy Study of Anti-NY-ESO-1 T Cell Receptor (TCR)-Gene Engineered Lymphocytes Given by Infusion to Patients With NY-ESO-1 -Expressing Metastatic Cancers
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 1, 2022 (Actual)
Primary Completion Date
December 30, 2027 (Anticipated)
Study Completion Date
December 30, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hadassah Medical Organization

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
A Phase I/II Dose Escalation, Safety and Efficacy Study of HBI 0201-ESO TCRT (anti-NY-ESO-1 TCR-Gene Engineered Lymphocytes) Given by Infusion to Patients with NY-ESO-1 -Expressing Metastatic Cancers
Detailed Description
This is a two-part, non-randomized, open label, single-site Phase I/II study. The first Part A is a dose ranging maximum tolerated dose (MTD) study and Part B is an extension phase to evaluate safety at the selected safe dose. A Data Safety Monitoring Board (DSMB) will determine the safe dose for testing in the expansion phase (Part B). Part A will be according to a 3+3 dose escalation design. A total of up to 20 patients will participate in this Part. Part B will be an expansion phase. The objective will be to determine if the treatment regimen is associated with a clinical response rate that can rule out 5% (p0=0.05) in favor of a modest 20% Partial Response (PR) + Complete Response (CR) rate (p1=0.20). A total of up to 43 patients may be enrolled in Part B (41 +2, allowing for up to 2 non-evaluable patients).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcoma, Synovial, Sarcoma,Soft Tissue, Melanoma Stage IV, Triple Negative Breast Cancer, Metastatic Cancer, Non Small Cell Lung Cancer, Bladder Urothelial Carcinoma, Neuroblastoma, Metastatic, Ovary Cancer
Keywords
NY-ESO-1, TCR, adoptive transfer, retroviral transduction

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
HBI 0201-ESO TCRT (Anti-NY-ESO-1 TCR-transduced peripheral blood lymphocytes)
Arm Type
Experimental
Arm Description
This is a two-part, non-randomized, open label, single-site Phase I/II study. The first Part A is a dose ranging maximum tolerated dose (MTD) study and Part B is an extension phase to evaluate safety at the selected safe dose. A Data Safety Monitoring Board (DSMB) will determine the safe dose for testing in the expansion phase (Part B). Part A will be according to a 3+3 dose escalation design. A total of up to 20 patients will participate in this Part. Part B will be an expansion phase. The objective will be to determine if the treatment regimen is associated with a clinical response rate that can rule out 5% (p0=0.05) in favor of a modest 20% Partial Response (PR) + Complete Response (CR) rate (p1=0.20). A total of up to 43 patients may be enrolled in Part B (41 +2, allowing for up to 2 non-evaluable patients).
Intervention Type
Drug
Intervention Name(s)
CYCLOPHOSPHAMIDE and FLUDARABIN
Other Intervention Name(s)
CYTOXAN
Intervention Description
1. CYCLOPHOSPHAMIDE 250 mg/msq, Day -5,-4,-3 with FLUDARABIN 25 mg/msq, Day -5,-4,-3
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
CYTOXAN
Intervention Description
CYCLOPHOSPHAMIDE 250 mg/msq, Day -6, -5,-4,-3
Intervention Type
Biological
Intervention Name(s)
HBI 0201-ESO TCRT
Intervention Description
HBI 0201-ESO TCRT will be infused on Day 0, after lymphodepletion. Three dose levels will be evaluated: 1x10E9, 5x10E9 and 1x10E10.
Intervention Type
Drug
Intervention Name(s)
Aldesleukin
Other Intervention Name(s)
Interleukin-2
Intervention Description
Continuous infusion of aldesleukin 18x10E6 IU/24h will be given 24 hours post HBI 0201-ESO TCRT infusion, for four days or until a dose limiting toxicity will occur that mimics cytokine release syndrome (CRS) including blood pressure drop, oliguria or confusion- all of them or any one alone.
Primary Outcome Measure Information:
Title
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Description
Adverse events that occur following engineered T cell transfer
Time Frame
5 years
Title
objective tumor regression
Description
change in index lesions' size
Time Frame
5 years
Secondary Outcome Measure Information:
Title
immune monitoring for transferred cells persistence
Description
blood test for ESO-TCRT cells' presence
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Have histologically or cytologically confirmed diagnosis of neoplasia Measurable (per RECIST v1.1 criteria) metastatic cancer or locally advanced refractory/recurrent malignancy not amenable to curative treatment. Lesions previously irradiated may be considered measurable only if growth has been documented since local treatment completion. The tumor expresses ESO as assessed immunohistochemistry of resected tissue. To this end, archived tumor tissue suitable for analysis must be available or re-biopsy performed on study. Tissue staining must encompass more than 10% of tumor section. Patients must have previously either (1) received at least first-line or second-line standard therapy for metastatic disease, if known to be effective for that disease, and have been either non-responders (progressive disease), intolerable or have recurred or (2) Recurred within 6 months of adjuvant systemic therapy known to be active also in the metastatic setting. Patients with 3 or fewer brain metastases that are less than 1 cm in diameter and asymptomatic are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for 1 month after treatment for the patient to be eligible. Patients with surgically resected brain metastases are eligible. More than four weeks must have elapsed since any prior systemic therapy at the time the patient receives the preparative regimen, and patients' toxicities must have recovered to a grade 1 or less (except for toxicities such as alopecia or vitiligo). Age ≥ 18 years and ≤ 70 years. Patient is able to understand and willing to sign a written informed consent. Clinical performance status of ECOG 0, 1 or 2. HLA-A*0201or A*0206 positive. Patients of both genders must be willing to practice birth control from the time of enrollment on this study and for four months after treatment. Women of child-bearing potential must have a negative pregnancy test. Serology: Seronegative for HIV antibody, hepatitis B antigen, and hepatitis C antibody. If hepatitis C antibody test is positive, then patient must be tested for the presence of antigen by RT-PCR and be HCV RNA negative. Hematology ANC > 1500/mm3 without the support of filgrastim WBC ≥ 3000/mm3 Platelet count ≥ 100,000/mm3 Hemoglobin > 8.0 g/dL. Subjects may be transfused to reach this cut-off. Chemistry Serum ALT/AST ≤ 2.5 x ULN Creatinine clearance ≥40ml/min Total bilirubin ≤ 1.5 mg/dL, except in patients with Gilbert's Syndrome, who must have a total bilirubin < 3.0 mg/dL. INR < 1.5 Exclusion Criteria: Women of child-bearing potential who are pregnant or breastfeeding. Any form of primary immunodeficiency (such as Severe Combined Immunodeficiency Disease). Active systemic infections requiring anti-infective treatment, coagulation disorders, or any other active or uncompensated major medical illnesses Concurrent systemic steroid therapy, not including replacement therapy or treatment with prednisone up to 10mg daily or its equivalent. Or any other form of immunosuppressive therapy within 7 days before the first dose of study intervention. History of severe immediate hypersensitivity reaction to cyclophosphamide, fludarabine, or aldesleukin. Subjects with a history of stroke, unstable angina, myocardial infarction, or ventricular arrhythmia requiring medication or mechanical control within 3 months. Subjects unable to maintain normal oxygen saturation level in room air. Subjects who have had a venous thromboembolic event requiring anticoagulation and who meet any of the following criteria: Have been on a stable dose of anticoagulation for < 1 month (except for acute line insertion induced thrombosis). Have had a Grade 2, 3, or 4 hemorrhage in the last 30 days or are experiencing continued symptoms from their venous thromboembolic event (e.g. continued dyspnea or oxygen requirement). Has a known additional malignancy within the last 3 years. Exceptions include early stage cancers (carcinoma in situ, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, in situ cervical cancer, or in situ breast cancer that has undergone potentially curative therapy). LVEF ≤ 40% Documented FEV1 ≤ 60% predicted tested in patients with: A prolonged history of cigarette smoking (≥ 20 pack-year smoking history, with cessation within the past two years). Symptoms of respiratory dysfunction. Patients who are at the time of study initiation receiving any other investigational agents. Carcinomatosis meningitis or other brain involvement exceeding that allowed above. Has received live vaccine within 30 days before the first dose of study intervention. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, chicken pox, yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michal Lotem, Prof.
Phone
+972058573528
Email
mlotem@hadassah.org.il
First Name & Middle Initial & Last Name or Official Title & Degree
Yafit Halutsi
Phone
+972526906339
Email
yafitha@hadassah.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Michal Lotem, MD
Organizational Affiliation
Hadassah Medical Organization
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hadassah Medical Organization
City
Jerusalem
ZIP/Postal Code
9112001
Country
Israel
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michal Lotem, Prof.
Phone
+972508573528
Email
mlotem@hadassah.org.il

12. IPD Sharing Statement

Learn more about this trial

Anti-NY-ESO-1 TCR-Gene Engineered Lymphocytes Given by Infusion to Patients With NY-ESO-1 -Expressing Metastatic Cancers

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