Relapsed or Refractory B cell Acute Lymphoblastic Leukemia after Haematopoietic Stem Cell Transplantation MedDRA version: 21.0 Level: LLT Classification code 10063625 Term: Acute lymphoblastic leukemia recurrent System Organ Class: 100000004864
Conditions
Interventions
Product Name: CARCIK-CD19
Product Code: PTG-CARCIK-CD19
Pharmaceutical Form: Suspension for injection
Current Sponsor code: PTG-CARCIK-CD19
Other descriptive name: CARCIK-CD19
Concentration unit: Othe
Sponsors
FONDAZIONE TETTAMANTI M.DE MARCHI ONLUS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Children and adults (1-75 years old); 2. Relapsed or refractory adult and pediatric B-cell precursor ALL after HSCT; 3. Evidence of CD19 tumor expression in bone marrow and/or peripheral blood by flow cytometry; 4. Bone marrow with = 5% lymphoblasts by morphologic assessment at screening ; 5. No evidence of overall aGVHD > Grade I or chronic GVHD (cGVHD) greater than mild at time of enrollment and in the previous 30 days; 6. No longer taking immunosuppressive agents for at least 30 days prior to enrollment; 7. No evidence of concomitant life-threatening infectious disease; 8. Life expectancy > 60 days; 9. Lansky/Karnofsky scores > 60; 10. Absence of severe renal disease (creatinine > x 3 normal for age); 11. Absence of severe hepatic disease (direct bilirubin > 3 mg/dl or SGOT > 500); 12. Patient/guardian able to give informed consent. 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 12 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 2
Exclusion criteria
Exclusion criteria: 1. Patients with GVHD Grades II-IV; 2. Any cell therapy in the last 30 days; 3. Patient with concomitant life-threatening infectious disease ; 4. Lansky/Karnofsky score <60; 5. Patients with hepatic or renal disease as specific above; 6. Pregnant or breast feeding females; 7. Rapidly progressive disease that in the estimation of the investigator and sponsor would compromise ability to complete study therapy; 8. Subjects must have recovered from the acute side effects of their prior therapy, such that eligibility criteria are met.; 9. HIV/HBV/HCV Infection: Seropositive for HIV antibody. Seropositive for hepatitis C or positive for Hepatitis B surface antigen (HBsAG); 10. Uncontrolled, symptomatic, intercurrent illness including but not limited to infection, congestive heart failure, unstable angina pectoris and cardiac arrhythmia; 11. Active Central Nervous System (CNS) involvement by malignancy, defined as CNS-3 per National Comprehensive Cancer Network (NCCN) guidelines. Note: Patients with history of CNS disease that has been effectively treated will be eligible 12. Patient has received an investigational medicinal product within the last 30 days prior to screening 13. Pregnant or nursing (lactating) women. NOTE: female study participants of reproductive potential must have a negative serum or urine pregnancy test performed within 48 hours before infusion 14. Women of child-bearing potential (defined as all women physiologically capable of becoming pregnant) and all male participants, unless they are using highly effective methods of contraception for a period of 1 year after the CARCIK-CD19 infusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1.To determine the Maximum Tolerated Dose (MTD) and the Recommended Phase 2 Dose (RP2D) of CARCIK-CD19 infusion 2.To assess the safety of CARCIK-CD19 infusion ;Secondary Objective: 1.To evaluate activity of CARCIK-CD19 administration as Overall Remission Rate (ORR) which includes Complete Remission (CR) and CR with incomplete blood count recovery (CRi) 2.To evaluate the duration of remission (DOR). 3.To evaluate relapse-free survival (RFS), event-free survival (EFS) and overall survival (OS). 4.To characterize the in vivo cellular pharmacokinetic (PK) profile (levels, persistence, trafficking) of CARCIK-CD19 cells in target tissues (blood, bone marrow, and other tissues if available). 5.To describe the levels of B and T cells (peripheral blood and bone marrow) prior to and following CARCIK-CD19 infusion for safety monitoring. 6.To describe the prevalence and incidence of immunogenicity to CARCIK-CD19.¿ ;Primary end point(s): 1.Dose Limiting Toxicities (DLT): rate and severity of the cytokine release syndrome (CRS) grade IV at 1 month; 2.Incidence of adverse events, serious adverse events, laboratory evaluations, vital signs, physical examination, and echocardiogram/electrocardiogram results. ;Timepoint(s) of evaluation of this end point: 1 month | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. The overall remission rate (ORR) at 1 and 6 months after CARCIK-CD19 administration, which includes CR and CR with incomplete blood count recovery (CRi). (See Section 12.5) 2. Duration of Reponse (DOR), i.e. the time from achievement of CR or CRi, whichever occurs first, to relapse or death due to ALL 3. Relapse Free Survival (RFS), i.e. the time from achievement of CR or CRi whichever occurs first to relapse or death due to any cause during CR or CRi 4. Event Free Survival (EFS), i.e. the time from date of CARCIK-CD19 infusion to the earliest of death, relapse or treatment failure 5. Overall Survival (OS), i.e. the time from date of CARCIK-CD19 infusion to the date of death due to any reason 6. Persistence of CARCIK-CD19 cells in target tissues (blood, bone marrow, and other tissues if available). 7. Levels of B and T cells (peripheral blood and bone marrow) prior to and following CARCIK-CD19 infusion for safety monitoring. 8. Prevalence and incidence of immunogenicity and anti- CARCIK-CD19 assay titers. ;Timepoint(s) of evaluation of this end point: 1,6,12 Months | — |
Countries
Italy
Contacts
Public ContactUNITA' RICERCA CLINICA
FONDAZIONE MBBM
Outcome results
None listed