CD19-CAR_Lenti in pediatric patients affected by relapsed/refractory B-ALL or aggressive B-NH
- Conditions
- relapsed/refractory CD19+ Acute Lymphoblastic Leukemia and Diffuse Large B Cell Lymphoma or Primary Mediastinal B Cell LymphomaMedDRA version: 20.0Level: SOCClassification code 10005329Term: Blood and lymphatic system disordersSystem Organ Class: 10005329 - Blood and lymphatic system disordersTherapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]
- Registration Number
- EUCTR2020-003452-32-IT
- Lead Sponsor
- IRCCS, OSPEDALE PEDIATRICO BAMBINO GESÙ DI ROMA
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 32
Procurement eligibility
1. Diagnosis of CD19 expressing B acute lymphoblastic leukemia (ALL) or diffuse large B-cell lymphoma (DLBCL) or primary mediastinal lymphoma (PML) and one of the following:
a. Patients in 1st relapse, with High-Risk (HR) features including: MLL-rearrangements, E2A/TCF3-PBX1 [t(1;19)], TCF3-HLF [t(17;19)], hypodiploidy (i.e., <44 chromosomes), TP53 alterations, early (i.e., <30 months from diagnosis)/very early (i.e.,
<18 months from diagnosis) isolated or combined bone marrow relapse
b. MRD > 0.1% after either reinduction therapy or any course of consolidation for relapsed ALL
c. Patients with DLBCL or PML in 1st or subsequent relapse, after at least one standard frontline chemotherapy
2. Age: 1 year – 25 years for BCP-ALL and 1-35 years for B-NHL.
3. Adequate venous access for apheresis or eligible for appropriate catheter placement, and no other contraindications for leukapheresis
4. Voluntary informed consent is given. For subjects < 18 year-old 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.
5. 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%.
Treatment eligibility (i.e., eligibility to drug product infusion)
1. Diagnosis of CD19 expressing B-ALL or DLBCL or PML and one of the following:
a. Patients in 1st relapse, with High-Risk (HR) features including: MLL-rearrangements, E2A/TCF3-PBX1, TCF3-HLF [t(17;19)], hypodiploidy (i.e., <44 chromosomes), TP53 alterations, early (i.e., <30 months from diagnosis)/very early (i.e., <18 months from diagnosis) isolated or combined bone marrow relapse
b. MRD > 0.1% after either reinduction therapy or any course of consolidation for relapsed
c. Patients with DLBCL or PML in 1st or subsequent relapse, after at least one standard frontline chemotherapy
2. Age: 1 year – 25 years for Bcp-ALL and 1-35 years for B-NHL.
3. Voluntary informed consent is given. For subjects < 18 year-old 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.
4. 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%.
5. Patients of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen.
6. Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.
Are the trial subjects under 18? yes
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 3
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
Procurement eligibility
1. Severe, uncontrolled active infections
2. HIV, or active HCV and/or HBV infection (detection of viral RNA/DNA in blood)
3. Previous allogeneic HSCT in the preceding 100 days before apheresis
4. Concurrent or recent prior therapies, before apheresis:
a) Systemic steroids (at a dose equivalent to or greater 2 mg/kg prednisone) in the 2 weeks before apheresis collection. Recent or current use of inhaled/topical/non-absorbable steroids is not exclusionary.
b) Systemic chemotherapy in the 2 weeks preceding apheresis collection.
c) Anti-thymocyte globulin (ATG) in the 4 weeks preceding apheresis collection.
d) Immunosuppressive agents in the 2 weeks preceding apheresis collection.
e) Radiation therapy must have been completed at least 1 week prior to apheresis.
f) Other anti-neoplastic investigational agents currently administered or within 30 days prior to apheresis (i.e., start of protocol therapy);
Treatment eligibility
1. Pregnant or lactating women
2. Severe, uncontrolled active infections
3. HIV, or active HCV and/or HBV infection (detection of viral RNA/DNA in blood)
4. Life-expectancy < 6 weeks
5. Hepatic function: Inadequate liver function defined as total bilirubin > 4x upper limit of normal (ULN) or transaminase (ALT and AST) > 6 x ULN
6. Renal function: serum creatinine > 3x ULN for age.
7. Blood oxygen saturation < 90%.
8. Cardiac function: Left ventricular ejection fraction lower than 45% by ECHO.
9. 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.
10. BM blasts > 50% pre-infusion.
11. Hyperleukocytosis (greater than or equal to 20,000 blasts/microliter) or rapidly progressive disease that in the evaluation of the investigator would compromise ability to complete study therapy
12. Presence of active, grade 2-4 acute or moderate-severe chronic GvHD
13. Recurrent or refractory ALL with testicular involvement
14. Concurrent or recent prior therapies, before infusion:
a) 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.
b) Systemic chemotherapy in the week preceding infusion.
c) Anti-thymocyte globulin (ATG) in the 4 weeks preceding infusion.
d) Immunosuppressive agents in the 1 week preceding infusion.
e) Radiation therapy must have been completed at least 3 weeks prior to enrollment.
f) Other anti-neoplastic investigational agents currently administered or within 30 days prior to infusion (i.e. start of protocol therapy);
15. Patient-derived CD19-CAR_Lenti production failure: vitality of the fresh product <80%, CD3+ cells <80%, CD3+ CAR+ cells <10%, non-sterility in IPC at day 5, endotoxin contamination (> 5 EU/ml) in IPC at day 5, mycoplasma contamination in IPC at day 5, failure of the visual inspection.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method