- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05128786
CCT301-38 CAR-T in Patients With Relapsed or Refractory AXL Positive Sarcomas
A Phase I Trial to Assess Safety, Tolerability and Anti-tumor Activity of Autologous T Cell Modified Chimeric Antigen Receptor (CAR) (CCT301-38) in Patients With Relapsed or Refractory AXL Positive Sarcomas
Study Overview
Detailed Description
This study is an open label, single-center Phase I dose escalation trial to assess the safety, tolerability, DLT and MTD of CCT301-38 cell therapy in patients with AXL positive relapsed or refractory sarcomas.
Subjects that meet inclusion criteria with positive AXL biopsy (IHC 1+ or greater in ≥50% tumor cells) will receive CCT301-38 according to the 3+3 dose escalation design.
Study Type
Enrollment (Anticipated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Yuhong Zhou, M.D.
- Phone Number: 2968 +86-21-64041990
- Email: zhou.yuhong@zs-hospital.sh.cn
Study Contact Backup
- Name: Wei Zhang, Ph.D.
- Phone Number: +86-17721010028
- Email: wzhang@perhum.com
Study Locations
-
-
Shanghai
-
Shanghai, Shanghai, China, 200032
- Recruiting
- Zhongshan Hospital affiliated to Fudan University
-
Contact:
- Yuhong Zhou, M.D.
- Phone Number: 2968 +86-21-64041990
- Email: zhou.yuhong@zs-hospital.sh.cn
-
Contact:
- Wei Zhang, Ph.D.
- Phone Number: +86-17721010028
- Email: wzhang@perhum.com
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Patients with willingness to be in the study and follow all study procedures, and capable of providing informed consent
- Male or female aged 18-70 years;
- Patients with unresectable, locally advanced or metastatic relapse/refractory sarcomas that have failed at least the front line standard treatment confirmed by histology or cytology;
- At least one measurable lesion, i.e. the length of non-lymph node lesions examined according to CT cross-sectional scanning or magnetic resonance imaging (MRI), or the short diameter of the lymph node lesions is ≥15 mm according to RECIST 1.1, and the FDG PET signal from the measurable lesion is > 3 SUV;
- Tumors with AXL positive (IHC 1+ or greater) in ≥50% of all tumor cells. A new biopsy is required if the sample is over one year.
- ECOG Performance Status 0-1;
- Expected survival greater than 12 weeks;
Adequate organ and hematopoietic system functions to meet the following requirements:
- Hemoglobin (HGB) s 90 g/L, no blood transfusions within two weeks;
- White blood cell (WBC) count≥2.5×109/L;
- Absolute Neutrophil Count (ANC) ≥1.5×109/L;
- Platelet (PLT) count ≥80×109/L;
- Total bilirubin (TBIL) ≤3.0ng/dL or ≤5 ULN;
- ALT and AST ≤5 ULN; for liver metastasis, ALT and AST ≤5 ULN
- Creatinine (Cr) ≤1.5 x ULN; or creatinine removal rate (CrCl) ≥50 mL/min;
- PT: INR < 1.7 or extended PT to normal value < 4s
- Normal language, recognition and consciousness assessed by investigator during screening phase;
- Capable of receiving treatment and follow-up, including treatment in the clinical center;
Exclusion Criteria:
- Females with pregnancy or in lactation period;
- Subjects with active hepatitis B, or active hepatitis C. Subjects with undetectable HBV DNA or HCV RNA after anti-virus treatment can be enrolled;
- HIV positive;
- Other active infections of clinical significance;
Subjects with the following previous or accompanying diseases:
• Subjects diagnosed as severe autoimmune diseases that require long term (more than 2 months) treatment with systemic immunosuppressants (steroids), or diseases with immune-mediated symptoms, including ulcerative colitis, Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus (SLE), and autoimmune vasculitis (e.g. Wegena granuloma);
- Patients with previous diagnosis as motor neuron disease caused by autoimmunity;
- Patients previously suffered from toxic epidermal necrolysis (TEN)
- Patients with any mental illness, including dementia, mental changes, which may cause difficulties understanding the informed consent and related questionnaires;
- Patients with serious uncontrollable diseases, which may interfere with the therapies in this study;
- Patients with other active malignancies in the past 5 years excluding those with completely cured basal or squamous skin cancers, superficial bladder cancers or primary breast cancers without need of follow-up treatment;
- Subjects receiving systemic steroids or steroid inhalants;
- Patients who have received tumor immunotherapy (including monoclonal antibody against PD-1, PD-L1, PD-L2, CD137 or CTLA-4, or cell therapy) in the past 4 weeks;
- Subjects allergic to immunotherapies or related drugs;
- Patients with metastatic lesions in meninges or central nervous system, or clear evidence of central nervous system diseases with continuous significant symptoms in the last 6 months;
- Patients with NYHA class II heart failure, or hypertension incontrollable by standard care, or medical history of myocarditis, or heart attack within a year;
- Subjects who have received or are going to receive organ transplantation;
- Patients with active bleeding;
- Patients with incontrollable pleural or abdominal fluid that needs clinical treatment or intervention;
- Patients as determined by the investigators to be inappropriate for the study.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CCT301-38
To determine the safety, tolerability, DLT and MTD of CCT301-38 cell therapy in patients with AXL-positive relapsed or refractory sarcomas.
|
Blood will be collected from subjects to isolate peripheral blood mononuclear cells for the production of CCT301-38.
Subjects will receive the conditioning chemotherapy regimen of cyclophosphamide and fludarabine for lymphodepletion followed by a single or multiple dose of CCT301-38 via intravenous injection.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
DLT
Time Frame: 28 days following infusion
|
To assess the safety and tolerability of CCT301-38 cell therapy for patients with AXL-positive (IHC 1+ or greater in ≥50% tumor cells) relapsed or refractory sarcomas.
|
28 days following infusion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
ORR
Time Frame: Up to 52 weeks
|
Proportion of subjects with the best overall response (BOR) of subjects with PR (partial response) and CR (complete response) as determined by local investigator using RECIST 1.1
|
Up to 52 weeks
|
DCR
Time Frame: Up to 52 weeks
|
Disease control rate: The proportion of subjects with CR (complete response), PR (partial response) or SD (stable disease lasting over 6 months) as determined by local investigator using RECIST 1.1.
|
Up to 52 weeks
|
DOR
Time Frame: Up to 52 weeks
|
Duration of response: The duration of time from record of response to first progression of disease as determined by RECIST 1.1 or death date not relevant to disease progression.
|
Up to 52 weeks
|
PFS
Time Frame: Up to 52 weeks
|
Progression free survival: The time of disease progression by RECIST 1.1 or death since cell infusion.
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Up to 52 weeks
|
TEAE
Time Frame: Up to 52 weeks
|
Number, severity and duration of treatment of emergent adverse events (TEAEs) that occur during treatment according to NCI-CTCAE v 5.0.
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Up to 52 weeks
|
PK
Time Frame: Up to 52 weeks
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The % of patients with detectable CCT301-38 cells in peripheral blood.
[Time Frame: Up to 52 weeks]
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Up to 52 weeks
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Biomarker
Time Frame: Up to 52 weeks
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To evaluate the correlation of AXL biopsy score to ORR. [Time Frame: Up to 52 weeks]
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Up to 52 weeks
|
Collaborators and Investigators
Collaborators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CCT301-38-SAR
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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