Ovarian CancerPhase 1/2NCT05211557
Study of Fully Human B7H3 CAR-T in Treating Recurrent Malignant Ovarian Cancer
A Phase 1/2 study testing fhB7H3.CAR-Ts in people with Ovarian Cancer, run by The Affiliated Hospital of Xuzhou Medical University at 1 site in China.
Trial summary
This is single center, open-label phase I, non-randomized study which will enroll patients with recurrent advanced ovarian cancer to evaluate the safety, feasibility, and efficacy of fully human B7H3 CAR-T cells (fhB7H3.CAR-Ts) via using a '3+3+3' dose escalation design. Read more about this study
- Who is it for?
- Ages 18 to 70 years, women only
- Conditions the study is for
- Ovarian Cancer
- What is being tested?
- fhB7H3.CAR-Ts
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteChina
- Study dates
- 16 Nov 2021to 31 Aug 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Procurement and T-cell production eligibility: a previously evaluation confirmed autologous peripheral blood mononuclear cells can be used for T-cell production
- Written informed consent and authorization for release of personal health information
- Subject has adequate performance status as defined by ECOG score of ≤ 2.
- Expected life expectancy is no less than 12 weeks.
- Subjects must have histologically or cytologically confirmed ovarian cancer. And cancer tissue or ascitic cancer cells are measured positive for B7H3 expression.
- Subjects must have recurrent or refractory disease after or during first-line treatment.
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- Defined as:
- Radiographic progression or Continuous Elevation of CA125.
- Subjects must have evaluable disease - defined as:
- Measurable disease with tumor length ≥ 10mm or enlarged lymph nodes ≥ 15mm according to RECIST v1.1 criteria.
- Adequate organ function - defined as:
- Blood routine:
- white blood cell count ≥ 3 × 10^9 / L; neutrophil count ≥ 1.5 × 10^9 / L; hemoglobin ≥ 9g/dL; platelet count ≥ 80 × 10^9 / L; INR< 1.5 × ULN; PT, APTT< 1.5 × ULN
- The liver, kidney, lung and cardiopulmonary function:
- Urea and serum creatinine ≤ 1.5 × ULN; Left ventricular ejection fraction ≥ 40%; Baseline oxygen saturation ≥ 95%; Total bilirubin ≤ 1.5 × ULN; ALT and AST ≤ 3 × ULN.
- Not pregnant with negative serum pregnancy test within 3 days prior to enrollment.
- Female subjects of childbearing potential must be willing to abstain from heterosexual activity or to use 2 forms of highly effective methods of contraception from the time of informed consent until 8 weeks after study treatment discontinuation.
- -
Who cannot join
- Subject has primary immunodeficiency syndrome or history of severe allergic reaction.
- Subject has active infection with HIV, HTLV, HBV, HCV.
- Subject has severe, uncontrolled intercurrent bacterial, viral or fungal infection.
- Subject has a history of gastrointestinal perforation, clinical and/or radiographic evidence of bowel obstruction, or intra-abdominal abscess within 3 months prior to starting treatment.
- Subject has active malignancy under treatment other than ovarian cancer.
- Subject has Grade ≥ 3 cardiac dysfunction or symptomatic arrhythmia requiring intervention.
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- Subject is current using of systemic corticosteroids at doses ≥10 mg prednisone daily or its equivalent.
- Subject has not recovered from toxicity of previous anti-tumor treatment (CTCAE 5.0).
- Subject is pregnant or breastfeeding.
- Unwilling or unable to provide consent/assent for participation in the study. -
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
The Affiliated Hospital of Xuzhou Medical University
Xuzhou, Jiangsu, 221002
Liantao Li, M.D., Ph.D., +86-516-85582530, liliantao@xzhmu.edu.cn
Xin Ding, M.D., Ph.D., +86-516-83355832, dingxin81@163.com
About this study
Official title: A Single-Arm, Open-Label Study to Evaluate Safety and Efficacy of Fully Human B7H3 CAR-T in Treating Patients With Recurrent Malignant Ovarian Cancer
This is single center, open-label phase I, non-randomized study which will enroll patients with recurrent advanced ovarian cancer to evaluate the safety, feasibility, and efficacy of fully human B7H3 CAR-T cells (fhB7H3.CAR-Ts) via using a '3+3+3' dose escalation design. In the dose expansion cohort, six patients will be enrolled to further assess their efficacy with the optimal dosage.
Read the detailed description
The purpose of this study is to test the safety and efficacy of a newly developed fully human scFv-armed B7H3 targeting chimeric antigen receptor T cells (fhB7H3.CAR-Ts), which are supposed to attack and eliminate B7H3-positive cancer cells. The patients who have been diagnosed as recurrent or relapsed malignant ovarian cancer, especially ovarian cancer patients with refractory ascites, will be potentially enrolled after assessing the expression of B7H3 antigen in tumor tissue by immunohistochemistry staining or ascitic tumor cells by flow cytometry.
After enrollment, participants' peripheral blood mononuclear cells will be collected and used to manufacture fhB7H3.CAR-Ts. Before infusion, the patients will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for three consecutive days. Two days later after lymphodepletion, the fhB7H3.CAR-Ts would be given through an abdominal catheter for intraperitoneal infusion. From the day of infusion, participants' peripheral blood and ascites will be collected twice a week in the first month for monitoring the survival of fhB7H3.CAR-Ts and evaluating the therapeutic efficacy. Additional follow-up and examination will be performed monthly for the first three month and then trimonthly until one year. Thereafter, annual follow-up will be completed for 5 years.
In addition, since the fhB7H3.CAR-Ts containing a RQR8 safety-switch which could be targeted and removed by Rituximab. Participants who experience life-threatening toxicities caused by uncontrollable proliferation of fhB7H3.CAR-Ts will receive infusion of Rituximab (Rituxan or Ruxience or Halpryza) to assess the ability of RQR8 safety-switch to eliminate infused fhB7H3.CAR-Ts.
This is an investigator-initiated clinical study to assess first-line clinical performance of novel fhB7H3.CAR-Ts which may help other advanced and recurrent ovarian cancer patients in the future.
- Conditions
- Ovarian Cancer
- Being tested
- fhB7H3.CAR-Ts
- Keywords
- Fully Human B7H3 CAR-T, Recurrent Ovarian Cancer
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
fhB7H3.CAR-TsBiological
Three dose levels will be evaluated: Dose Level 1 (1×10^6/kg), dose Level 2 (3×10^6/kg) and dose Level 3 (5×10^6/kg). If dose limiting toxicities (DLTs) are observed in each doses, Dose Level -1 (0.5×10^6/kg /infusion) will be evaluated.
Other Name: B7H3 targeting chimeric antigen receptor T cells Drug: Fludarabine 30 mg/m2 i.v. for 3 consecutive days (Day -5~Day -3) Other Name: FLUDARA Drug: Cyclophosphamide 750 mg/m2 i.v. for once (Day -5) Other Name: Cytoxan
| Study group | Role | What they receive |
|---|---|---|
| fhB7H3.CAR-T cells | Experimental | In phase I study, 9 enrolled patients diagnosed with advanced ovarian cancer will receive one-time infusion of fhB7H3.CAR-Ts at the doses of 1×10^6/kg, 3×10^6/kg and 5×10^6/kg, 3 patients for each dose. To further confirm the therapeutic efficacy, in phase II study, 6 enrolled patients will receive an optimal dose (balancing effectiveness and toxicity) of fhB7H3.CAR-Ts. Prior to receiving the infusions, patients will undergo lymphodepletion with fludarabine and cyclophosphamide. Receives: Biological: fhB7H3.CAR-Ts |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicity of fully human B7H3 CAR-T cells
Dose limiting toxicity (DLT), including the type, frequency, severity and duration of adverse events, such as cytokine release syndrome (CRS), on-target off-tumor, immune effector cell-associated neurotoxicity syndrome, will be monitored and assessed.
Measured: 1 month
Objective response of fully human B7H3 CAR-T cells
Objective response rate (ORR) including complete response (CR), partial response (PR), and/or stable disease, will be determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
Complete Response (CR): disappearance of all target lesions. Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD): no response or less response than Partial or Progressive.
Progressive Disease (PD): 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
Measured: 1 month
Secondary outcomes (1)
In vivo persistence of fully human B7H3 CAR-T cells
Presence and number of CAR T cells in the peripheral blood and ascites will be assessed.
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2022
- Study start16 Nov 2021
- Primary completion31 Aug 2023 (estimated)
- Study completion31 Aug 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Affiliated Hospital of Xuzhou Medical University
- Sponsor type
- University, hospital or other
- Collaborators
- Xuzhou Medical University, IIT MediTech (Jiangsu) Co. Ltd
- Responsible party
- Sponsor
- Investigators
- Junnian Zheng, M.D., Ph.D., Study director, The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical UniversityLongzhen Zhang, M.D., Ph.D., Principal investigator, The Affiliated Hospital of Xuzhou Medical UniversityGang Wang, Ph.D., Principal investigator, Xuzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05211557
- Sponsor's protocol ID
- XYFY2021-KL184-01
- Status last verified
- Jan 2022
- First submitted
- 13 Jan 2022
- Last updated
- 27 Jan 2022
- 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 27 Jan 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Single-Arm, Open-Label Study to Evaluate Safety and Efficacy of Fully Human B7H3 CAR-T in Treating Patients With Recurrent Malignant Ovarian Cancer
- ClinicalTrials.gov ID
- NCT05211557
- Acronym / sponsor ID
- XYFY2021-KL184-01
- Conditions
- Ovarian Cancer
- Keywords
- Fully Human B7H3 CAR-T, Recurrent Ovarian Cancer
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- The Affiliated Hospital of Xuzhou Medical UniversityUniversity, hospital or other
- Collaborators
- Xuzhou Medical University, IIT MediTech (Jiangsu) Co. Ltd
- Study start
- 16 Nov 2021 (actual)
- Primary completion
- 31 Aug 2023 (estimated)
- Study completion
- 31 Aug 2026 (estimated)
- First posted
- 27 Jan 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.
This is single center, open-label phase I, non-randomized study which will enroll patients with recurrent advanced ovarian cancer to evaluate the safety, feasibility, and efficacy of fully human B7H3 CAR-T cells (fhB7H3.CAR-Ts) via using a '3+3+3' dose escalation design. In the dose expansion cohort, six patients will be enrolled to further assess their efficacy with the optimal dosage.
Detailed description
The purpose of this study is to test the safety and efficacy of a newly developed fully human scFv-armed B7H3 targeting chimeric antigen receptor T cells (fhB7H3.CAR-Ts), which are supposed to attack and eliminate B7H3-positive cancer cells. The patients who have been diagnosed as recurrent or relapsed malignant ovarian cancer, especially ovarian cancer patients with refractory ascites, will be potentially enrolled after assessing the expression of B7H3 antigen in tumor tissue by immunohistochemistry staining or ascitic tumor cells by flow cytometry.
After enrollment, participants' peripheral blood mononuclear cells will be collected and used to manufacture fhB7H3.CAR-Ts. Before infusion, the patients will receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine for three consecutive days. Two days later after lymphodepletion, the fhB7H3.CAR-Ts would be given through an abdominal catheter for intraperitoneal infusion. From the day of infusion, participants' peripheral blood and ascites will be collected twice a week in the first month for monitoring the survival of fhB7H3.CAR-Ts and evaluating the therapeutic efficacy. Additional follow-up and examination will be performed monthly for the first three month and then trimonthly until one year. Thereafter, annual follow-up will be completed for 5 years.
In addition, since the fhB7H3.CAR-Ts containing a RQR8 safety-switch which could be targeted and removed by Rituximab. Participants who experience life-threatening toxicities caused by uncontrollable proliferation of fhB7H3.CAR-Ts will receive infusion of Rituximab (Rituxan or Ruxience or Halpryza) to assess the ability of RQR8 safety-switch to eliminate infused fhB7H3.CAR-Ts.
This is an investigator-initiated clinical study to assess first-line clinical performance of novel fhB7H3.CAR-Ts which may help other advanced and recurrent ovarian cancer patients in the future.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| fhB7H3.CAR-T cells | Experimental | Biological: fhB7H3.CAR-TsIn phase I study, 9 enrolled patients diagnosed with advanced ovarian cancer will receive one-time infusion of fhB7H3.CAR-Ts at the doses of 1×10^6/kg, 3×10^6/kg and 5×10^6/kg, 3 patients for each dose. To further confirm the therapeutic efficacy, in phase II study, 6 enrolled patients will receive an optimal dose (balancing effectiveness and toxicity) of fhB7H3.CAR-Ts. Prior to receiving the infusions, patients will undergo lymphodepletion with fludarabine and cyclophosphamide. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Procurement and T-cell production eligibility: a previously evaluation confirmed autologous peripheral blood mononuclear cells can be used for T-cell production
- Written informed consent and authorization for release of personal health information
- Subject has adequate performance status as defined by ECOG score of ≤ 2.
- Expected life expectancy is no less than 12 weeks.
- Subjects must have histologically or cytologically confirmed ovarian cancer. And cancer tissue or ascitic cancer cells are measured positive for B7H3 expression.
Key exclusion criteria (10 listed)
- Subject has primary immunodeficiency syndrome or history of severe allergic reaction.
- Subject has active infection with HIV, HTLV, HBV, HCV.
- Subject has severe, uncontrolled intercurrent bacterial, viral or fungal infection.
- Subject has a history of gastrointestinal perforation, clinical and/or radiographic evidence of bowel obstruction, or intra-abdominal abscess within 3 months prior to starting treatment.
- Subject has active malignancy under treatment other than ovarian cancer.
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 |
|---|---|---|
| fhB7H3.CAR-TsThree dose levels will be evaluated: Dose Level 1 (1×10^6/kg), dose Level 2 (3×10^6/kg) and dose Level 3 (5×10^6/kg). If dose limiting toxicities (DLTs) are observed in each doses, Dose Level -1 (0.5×10^6/kg /infusion) will be evaluated. Other Name: B7H3 targeting chimeric antigen receptor T cells Drug: Fludarabine 30 mg/m2 i.v. for 3 consecutive days (Day -5~Day -3) Other Name: FLUDARA Drug: Cyclophosphamide 750 mg/m2 i.v. for once (Day -5) Other Name: Cytoxan | Biological | fhB7H3.CAR-T cells |
Primary outcome
Dose limiting toxicity of fully human B7H3 CAR-T cells
Time frame: 1 month
Dose limiting toxicity (DLT), including the type, frequency, severity and duration of adverse events, such as cytokine release syndrome (CRS), on-target off-tumor, immune effector cell-associated neurotoxicity syndrome, will be monitored and assessed.
Objective response of fully human B7H3 CAR-T cells
Time frame: 1 month
Objective response rate (ORR) including complete response (CR), partial response (PR), and/or stable disease, will be determined by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Complete Response (CR): disappearance of all target lesions. Partial Response (PR): >=30% decrease in the sum of the longest diameter of target lesions. Stable Disease (SD): no response or less response than Partial or Progressive. Progressive Disease (PD): 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions.
1 secondary outcome
In vivo persistence of fully human B7H3 CAR-T cells
Time frame: 1 month
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2022.
- 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. This study is not recruiting at the moment.
Junnian Zheng, M.D., Ph.D. study director
The Affiliated Hospital of Xuzhou Medical University, Xuzhou Medical University
Longzhen Zhang, M.D., Ph.D. principal investigator
The Affiliated Hospital of Xuzhou Medical University
Gang Wang, Ph.D. principal investigator
Xuzhou Medical University
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 fhB7H3.CAR-Ts in people with Ovarian Cancer, run by The Affiliated Hospital of Xuzhou Medical University at 1 site in China.
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 18 inclusion and 10 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: status not confirmed, as of the sponsor's last update on 27 Jan 2022. 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 China. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Liantao Li, M.D., Ph.D. (+86-516-85582530, liliantao@xzhmu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose limiting toxicity of fully human B7H3 CAR-T cells (time frame: 1 month). 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 27 Jan 2022.