Sarcoma, SynovialPhase 1/2NCT05296564
Anti-NY-ESO-1 TCR-Gene Engineered Lymphocytes Given by Infusion to Patients With NY-ESO-1 -Expressing Metastatic Cancers
A Phase 1/2 study testing CYCLOPHOSPHAMIDE and FLUDARABIN, Cyclophosphamide and HBI 0201-ESO TCRT in people with Sarcoma, Synovial and Sarcoma,Soft Tissue, run by Hadassah Medical Organization at 1 site in Israel.
Trial 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 Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Sarcoma, Synovial, Sarcoma,Soft Tissue, Melanoma Stage IV
- What is being tested?
- CYCLOPHOSPHAMIDE and FLUDARABIN, Cyclophosphamide and HBI 0201-ESO TCRT
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Apr 2022to 30 Dec 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Israel1 site, 1 recruiting
- Recruiting
Hadassah Medical Organization
Jerusalem, 9112001
Michal Lotem, Prof., +972508573528, mlotem@hadassah.org.il
About this study
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
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
Read the 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).
- Conditions
- Sarcoma, Synovial, Sarcoma,Soft Tissue, Melanoma Stage IV, Triple Negative Breast Cancer, Metastatic Cancer, Non Small Cell Lung Cancer
- Being tested
- CYCLOPHOSPHAMIDE and FLUDARABIN, Cyclophosphamide, HBI 0201-ESO TCRT, Aldesleukin
- Keywords
- NY-ESO-1, TCR, adoptive transfer, retroviral transduction
- Medical subject headings
- Sarcoma, Synovial, Sarcoma, Melanoma, Triple Negative Breast Neoplasms, Neoplasm Metastasis, Carcinoma, Non-Small-Cell Lung, Neuroblastoma, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CYCLOPHOSPHAMIDE and FLUDARABINDrug
Also called CYTOXAN
- CYCLOPHOSPHAMIDE 250 mg/msq, Day -5,-4,-3 with FLUDARABIN 25 mg/msq, Day -5,-4,-3
CyclophosphamideDrug
Also called CYTOXAN
CYCLOPHOSPHAMIDE 250 mg/msq, Day -6, -5,-4,-3
HBI 0201-ESO TCRTBiological
HBI 0201-ESO TCRT will be infused on Day 0, after lymphodepletion. Three dose levels will be evaluated: 1x10E9, 5x10E9 and 1x10E10.
AldesleukinDrug
Also called Interleukin-2
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.
| Study group | Role | What they receive |
|---|---|---|
| HBI 0201-ESO TCRT (Anti-NY-ESO-1 TCR-transduced peripheral blood lymphocytes) | Experimental | 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). Receives: Drug: CYCLOPHOSPHAMIDE and FLUDARABIN; Drug: Cyclophosphamide; Biological: HBI 0201-ESO TCRT; Drug: Aldesleukin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Adverse events that occur following engineered T cell transfer
Measured: 5 years
objective tumor regression
change in index lesions' size
Measured: 5 years
Secondary outcomes (1)
immune monitoring for transferred cells persistence
blood test for ESO-TCRT cells' presence
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2022
- Study start1 Apr 2022
- Primary completion30 Dec 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sarcoma, SynovialStudies of the same condition, open and under way.
- More trials run by Hadassah Medical OrganizationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Michal Lotem, MD, Principal investigator, Hadassah Medical Organization
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05296564
- Sponsor's protocol ID
- 0752-20-HMO
- Status last verified
- Mar 2025
- First submitted
- 22 Feb 2022
- Last updated
- 2 Oct 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05296564
- Acronym / sponsor ID
- 0752-20-HMO
- Conditions
- Sarcoma, Synovial, Sarcoma,Soft Tissue, Melanoma Stage IV, Triple Negative Breast Cancer, Metastatic Cancer, Non Small Cell Lung Cancer
- Keywords
- NY-ESO-1, TCR, adoptive transfer, retroviral transduction
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 3 participants (estimated)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Study start
- 1 Apr 2022 (actual)
- Primary completion
- 30 Dec 2027 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 25 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HBI 0201-ESO TCRT (Anti-NY-ESO-1 TCR-transduced peripheral blood lymphocytes) | Experimental | Drug: CYCLOPHOSPHAMIDE and FLUDARABIN, Drug: Cyclophosphamide, Biological: HBI 0201-ESO TCRT, Drug: AldesleukinThis 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). |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- 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.
Key exclusion criteria (18 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CYCLOPHOSPHAMIDE and FLUDARABINAlso: CYTOXAN1. CYCLOPHOSPHAMIDE 250 mg/msq, Day -5,-4,-3 with FLUDARABIN 25 mg/msq, Day -5,-4,-3 | Drug | HBI 0201-ESO TCRT (Anti-NY-ESO-1 TCR-transduced peripheral blood lymphocytes) |
| CyclophosphamideAlso: CYTOXANCYCLOPHOSPHAMIDE 250 mg/msq, Day -6, -5,-4,-3 | Drug | HBI 0201-ESO TCRT (Anti-NY-ESO-1 TCR-transduced peripheral blood lymphocytes) |
| HBI 0201-ESO TCRTHBI 0201-ESO TCRT will be infused on Day 0, after lymphodepletion. Three dose levels will be evaluated: 1x10E9, 5x10E9 and 1x10E10. | Biological | HBI 0201-ESO TCRT (Anti-NY-ESO-1 TCR-transduced peripheral blood lymphocytes) |
| AldesleukinAlso: Interleukin-2Continuous 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. | Drug | HBI 0201-ESO TCRT (Anti-NY-ESO-1 TCR-transduced peripheral blood lymphocytes) |
Primary outcome
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability]
Time frame: 5 years
Adverse events that occur following engineered T cell transfer
objective tumor regression
Time frame: 5 years
change in index lesions' size
1 secondary outcome
immune monitoring for transferred cells persistence
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Oct 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Michal Lotem, MD principal investigator
Hadassah Medical Organization
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing CYCLOPHOSPHAMIDE and FLUDARABIN, Cyclophosphamide and HBI 0201-ESO TCRT in people with Sarcoma, Synovial and Sarcoma,Soft Tissue, run by Hadassah Medical Organization at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 23 inclusion and 18 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 2 Oct 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michal Lotem, Prof. (+972058573528, mlotem@hadassah.org.il), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] (time frame: 5 years). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Oct 2025.