Paediatric patients with B-cell acute lymphoblastic leukaemia and lymphoma who are refractory, relapsed to prior treatments
Conditions
Interventions
Product Code: CTL019
Pharmaceutical Form: Dispersion for infusion
INN or Proposed INN: tisagenlecleucel
Current Sponsor code: CTL019
Other descriptive name: TISAGENLECLEUCEL-T
Concentration unit: Othe
Sponsors
Novartis Pharmaceuticals
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: •Relapsed or refractory pediatric B-cell ALL: 1.2nd or greater Bone Marrow (BM) relapse OR 2.Any BM relapse after allogeneic SCT and must be > 6 months from SCT at the time of CTL019 infusion OR 3.Refractory as defined by not achieving a CR (morphology 60 mL/min/1.73 m2 OR serum creatinine based on age/gender; 2.Alanine Aminotransferase (ALT) 91% on room air 5.Left Ventricular Shortening Fraction (LVSF) = 28% confirmed by echocardiogram, or Left Ventricular Ejection Fraction (LVEF) = 45% confirmed by echocardiogram or MUGA •Bone marrow with = 5% lymphoblasts by morphologic assessment at screening •Life expectancy > 12 weeks •Age 2 at the time of initial diagnosis to age 21 at the time of initial diagnosis •Karnofsky (age = 16 years) or Lansky (age =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: •Isolated extra-medullary disease relapse •Patients with concomitant genetic syndrome: such as patients with Fanconi anemia, Kostmann syndrome, Shwachman syndrome or any other known bone marrow failure syndrome. Patients with Down Syndrome will not be excluded. •Patients with Burkitt's lymphoma/leukemia (i.e. patients with mature B-cell ALL, leukemia with B-cell [surface Immunoglobulin (sIg) positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation) •Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease •Prior treatment with gene therapy product •Treatment with any prior anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy •Active or latent hepatitis B or active hepatitis C, or any uncontrolled infection at screening •HIV infection at screening •Presence of grade 2 to 4 acute or extensive chronic graft-versus-host disease (GVHD) •The following medications are excluded: 1.Steroids: Therapeutic doses of steroids must be stopped > 72 hours prior to CTL019 infusion. However, the following physiological replacement doses of steroids are allowed: 6 weeks prior to CTL019 infusion; 3.GVHD therapies: Any drug used for GVHD must be stopped > 4 weeks prior to CTL019 infusion (e.g. calcineurin inhibitors, methotrexate or other chemotherapy drugs, mycophenolyate, steroids [see above] rapamycin, thalidomide, or immunosuppressive antibodies such as rituximab anti-CD20 (rituximab), anti-TNF, anti-IL6, or anti-IL6R; 4.Chemotherapy: i. The following drugs must be stopped > 1 week prior to CTL019 infusion and should not be administered concomitantly or following lymphodepleting chemotherapy: hydroxyurea, vincristine, 6-mercaptopurine, 6-thioguanine, methotrexate 4 weeks prior to CTL019 infusion: salvage chemotherapy (e.g. clofarabine, cytosine arabinoside > 100 mg/m2, anthracyclines, cyclophosphamide), excluding the required lymphodepleting chemotherapy drugs; 5.CNS disease prophylaxis: i. CNS prophylaxis treatment must be stopped > 1 week prior to CTL019 infusion (e.g. intrathecal methotrexate). •Active 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 eligible12. Patient has participated in an investigational research study using an investigational agent within the last 30 days prior to screening •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 •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 CTL019 infusion). Highly effective contraception methods include: 1.Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are NOT acceptable methods of contraception); 2.Female
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: •Overall Remission Rate (ORR) [ Time Frame: within 6 months after CTL019 administration ] ;Secondary Objective: Overall Remission Rate (ORR), which includes Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi), as determined by assessments of peripheral blood, bone marrow, CNS symptoms, physical exam (PE) and cerebrospinal fluid (CSF). The primary endpoint was based on the independent review committee (IRC) assessment. •Safety [ Time Frame: 12 months ] Adverse events and laboratory abnormalities (type, frequency and severity) ;Primary end point(s): •Overall Remission Rate (ORR) ;Timepoint(s) of evaluation of this end point: [ Time Frame: within 6 months after CTL019 administration ] | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Overall Remission Rate (ORR), which includes Complete Remission (CR) and Complete Remission with Incomplete Blood Count Recovery (CRi), as determined by assessments of peripheral blood, bone marrow, CNS symptoms, physical exam (PE) and cerebrospinal fluid (CSF). The primary endpoint was based on the independent review committee (IRC) assessment. •Safety Adverse events and laboratory abnormalities (type, frequency and severity) ;Timepoint(s) of evaluation of this end point: Safety [ Time Frame: 12 months ] | — |
Countries
United States
Contacts
Public ContactClinical Trial Information Desk
Novartis Pharma AG
Outcome results
None listed