- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06064903
CD7-CAR-T Cells in Pediatric Relapsed/Refractory CD7+ T-ALL/LL (CD7-CAR01)
Phase I/II Study of Anti-CD7 Chimeric Antigen Receptor-Expressing T Cells in Pediatric Patients Affected by Relapsed/Refractory CD7+ T-cell Acute Lymphoblastic Leukemia/Lymphoma
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Franco Locatelli, MD, PhD
- Phone Number: 2678 +3966859
- Email: franco.locatelli@opbg.net
Study Contact Backup
- Name: Francesca Del Bufalo, MD, PhD
- Phone Number: 2739 +3966859
- Email: francesca.delbufalo@opbg.net
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Child
- Adult
Accepts Healthy Volunteers
Description
Procurement eligibility
Inclusion Criteria:
Diagnosis of CD7 expressing (> 98% CD7 expression on blast cells) T-ALL or LL and one of the following:
- Patients in 1st or subsequent relapse, after at least one standard frontline chemotherapy with BM involvement (MRD >1% in 2 consecutive determinations or evidence of morphological relapse, i.e. >5% blasts in BM);
- Relapse after allogeneic HSCT, if at least 100 days post-transplant, if there is no evidence of active GVHD and if the patient is no longer taking immunosuppressive agents for at least 30 days prior to enrollment;
- CNS disease as defined as > 5 WBCs/mcL in CSF with morphological/flow-cytometry evidence of blasts or biopsy proven recurrence in the eye or brain;
- Extramedullary relapse as defined by morphological evidence of blasts in the testis or any other extramedullary sites;
- Refractory disease, defined as MRD ≥ 1% or <1% but persistently positive (i.e. a positive MRD value confirmed by PCR at 2 subsequent evaluations performed at least 2 weeks apart), at the end of consolidation blocks in newly diagnosed patients;
- Age: 6 months - 25 years.
- Adequate venous access for apheresis or eligible for appropriate catheter placement, and no other contraindications for leukapheresis.
- Voluntary informed consent is given. For subjects <18-year-old, or below the age required by each Country regulation, their legal guardian must give informed consent. Pediatric subjects will be included in age-appropriate discussion and verbal assent will be obtained for those greater than or equal to 12 years of age, when appropriate, or to sign age-adapted informed consent, according to the regulatory requirement of each Country.
- Clinical performance status: Patients > 16 years of age: Karnofsky greater than or equal to 60%; Patients < 16 years of age: Lansky scale greater than or equal to 60%.
Exclusion Criteria:
- Severe, uncontrolled active intercurrent infections.
- HIV, or active HCV and/or HBV infection.
- Blast contamination in peripheral blood >5%, by flow-cytometry, at the time of leukapheresis collection.
Concurrent or recent prior therapies, before apheresis:
- Systemic steroids (at a dose equivalent to or greater than 2 mg/kg prednisone) in the 2 weeks before apheresis collection. Recent or current use of inhaled/topical/non-absorbable steroids is not exclusionary
- Systemic chemotherapy in the 2 weeks preceding apheresis collection
- Nelarabine, daratumomab, clofarabine exposure in the 3 weeks preceding apheresis collection
- Anti-thymocyte globulin (ATG) or Alemtuzumab (Campath®) in the 8 weeks preceding apheresis collection
- Immunosuppressive agents in the 2 weeks preceding apheresis collection
- Radiation therapy must have been completed at least 2 weeks prior to apheresis
- Other anti-neoplastic investigational agents currently administered or within 30 days prior to apheresis (i.e. start of protocol therapy)
Exceptions:
- There is no time restriction with regard to prior intrathecal chemotherapy, provided that there is complete recovery from any acute toxic effects of such chemotherapy;
- Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study provided they meet all other eligibility criteria;
- Subjects receiving steroid therapy at physiologic replacement doses only are allowed provided there has been no increase in dose for at least 2 weeks prior to starting apheresis.
Treatment eligibility
Inclusion criteria:
Diagnosis of CD7 expressing (> 98% CD7 expression on blast cells) T-ALL or LL and one of the following:
- Patients in 1st or subsequent relapse, after at least one standard frontline chemotherapy with BM involvement (MRD >1% in 2 consecutive determinations or evidence of morphological relapse, i.e. >5% blasts in BM)
- Relapse after allogeneic HSCT, if at least 100 days post-transplant, if there is no evidence of active GVHD and if the patient is no longer taking immunosuppressive agents for at least 30 days prior to enrollment
- CNS disease as defined as > 5 WBCs/mcL in CSF with morphological or flow-cytometry evidence of blasts or biopsy proven recurrence in the eye or brain
- Extramedullary relapse as defined by morphological evidence of blasts in the testis or any other extramedullary sites
- Refractory disease, defined as MRD ≥1% or <1% but persistently positive (i.e. a positive MRD value confirmed by PCR at 2 subsequent evaluations performed at least 2 weeks apart), at the end of consolidation blocks in newly diagnosed patients
- Measurable or evaluable disease at the time of enrollment, which may include any evidence of disease, including MRD detected by flow-cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
- Age: 6 months - 25 years.
- Before enrollment for treatment, patients must have a potential allogeneic hematopoietic stem cell (HSC) donor (matched related, matched unrelated or haploidentical) available.
- Voluntary informed consent is given. For subjects <18-year-old, or below the age required according to each Country regulation, their legal guardian must give informed consent. Pediatric subjects will be included in age-appropriate discussion and verbal assent will be obtained for those greater than or equal to 12 years of age, when appropriate, or to sign age-adapted informed consent, according to the regulatory requirement of the Country.
- Clinical performance status: Patients > 16 years of age: Karnofsky greater than or equal to 60%; Patients < 16 years of age: Lansky scale greater than or equal to 60%.
Exclusion criteria:
- Pregnant or lactating women.
- Severe, uncontrolled active intercurrent infections.
- HIV, or active HCV and/or HBV infection.
- Life-expectancy < 6 weeks.
- Hepatic function: Inadequate liver function defined as total bilirubin > 4x upper limit of normal (ULN) or transaminase (ALT and AST) > 6 x ULN.
- Renal function: serum creatinine > 3x ULN for age.
- Blood oxygen saturation < 90%.
- Cardiac function: Left ventricular ejection fraction lower than 45% by ECHO.
- Congestive heart failure, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the subject.
- Uncontrolled seizures or status epilepticus; increased intra-cranial pressure as evidenced by papilledema and CSF opening pressure > 20 cm water; decreased conscious state (any cause).
- Contamination of either the apheresis collection or the CD7-CART01 drug product with >5% blasts.
- Presence of active, grade 2-4 acute or extensive chronic GvHD.
Concurrent or recent prior therapies, before infusion:
- Systemic steroids (at a dose > 2 mg/kg prednisone) in the 2 weeks before infusion. Recent or current use of inhaled/topical/non-absorbable steroids is not exclusionary
- Systemic chemotherapy in the 2 weeks preceding infusion
- Anti-thymocyte globulin (ATG) or Alemtuzumab (Campath®) in the 8 weeks preceding infusion
- Immunosuppressive agents in the 2 weeks preceding infusion
- Radiation therapy must have been completed at least 3 weeks prior to enrollment
- Other anti-neoplastic investigational agents currently administered or within 30 days prior to infusion (i.e., start of protocol therapy)
Exceptions:
- There is no time restriction in regards to prior intrathecal chemotherapy but there must be a complete recovery from any acute toxic effects from such chemotherapy;
- Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study provided that they meet all other eligibility criteria;
- Subjects receiving steroid therapy at physiologic replacement doses only are allowed provided that there has been no increase in dose for at least 2 weeks prior to starting apheresis.
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: CD7-CART01
A single IV infusion of CD7-CART01 (CD7-directed chimeric antigen receptor T-cells) on Day 0 after lymphodepleting regimen. Patients will receive the following lymphodepleting regimen:
CD7-CART01 will be infused at the following dose levels:
If 2 DLTs are observed an additional DL0 of 0.25 x 106 CAR+ cells /kg will be explored. |
A single IV infusion of CD7-CART01 on Day 0
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety (Phase I) and definition of the recommended dose (Phase I)
Time Frame: 28 days
|
To evaluate the safety of the infusion of CD7-CART01, explore the dose-limiting toxicities (DLT) of the cellular product and define the recommended dose of CD7-CART01, defined as the maximum tolerated dose/recommended dose (MTD/RD), to be evaluated for efficacy in the phase II extension
|
28 days
|
Antitumor effect of CD7-CART01 (Phase II)
Time Frame: 28 days
|
To evaluate the portion of patients achieving either BM, PB and CSF morphological complete remission (CR) or CR with incomplete blood count recovery (CRi) and with minimal residual disease (MRD) negativity at day 28
|
28 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of participants with treatment-related adverse events as assessed by CTCAE v5.0
Time Frame: 28 days
|
In the phase II portion of the study, the treatment-related adverse events will be recorded
|
28 days
|
Antitumor effect of CD7-CART01 (Phase I and II)
Time Frame: 28 days
|
To assess the Overall Response Rate (ORR) at day 28
|
28 days
|
In vivo persistence of CD7-CART01 (Phase I and II)
Time Frame: 3 years
|
To assess the in vivo persistence of the infused T cells using immunoassays and transgene detection (flow-cytometry and Real Time qPCR)
|
3 years
|
Relative proportion and phenotype of CD3+CAR+ T cells/CD3+CAR- T cells/NK cells (Phase I and II)
Time Frame: 3 years
|
To assess the relative proportion and phenotype of CD3+CAR+ T cells/CD3+CAR- T cells/NK cells at day +28 and whenever it will be the case at subsequent time points
|
3 years
|
Assessment of cumulative incidence of relapse
Time Frame: 3 years
|
To assess the cumulative incidence of both molecular and morphological relapse (defined as an MRD >10^-4 and a BM blast percentage > 5%, respectively)
|
3 years
|
Assessment of cumulative incidence of overall survival
Time Frame: 3 years
|
To assess the cumulative incidence of overall survival at 1 and 3 years post cell infusion
|
3 years
|
Assessment of cumulative incidence of disease-free survival
Time Frame: 3 years
|
To assess the cumulative incidence of disease-free survival at 1 and 3 years post cell infusion
|
3 years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Franco Locatelli, MD, PhD, Director Department of Hematology/Oncology and Cell and Gene Therapy
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
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
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- CD7-CAR01
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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