A clinical study to determine the efficacy and safety of tisagenlecleucel, an investigational therapy, in first-line high-risk children and adolescent/young adult patients with B-cell acute lymphoblastic leukemia who are minimal residual disease positive at the end of consolidation therapy

Phase 1

• Conditions: Pediatric and young adult patients aged 1 to 25 years with first-line NCI high-risk (HR) B-cell acute lymphoblastic leukemia (B-ALL) who are in CR1 with minimal residual disease (MRD) positive (MRD = 0.01%) at the end of consolidation (EOC) therapy by central laboratory assessment.; MedDRA version: 20.0 Level: LLT Classification code 10063625 Term: Acute lymphoblastic leukemia recurrent System Organ Class: 100000004864; MedDRA version: 20.0 Level: LLT Classification code 10063621 Term: Acute lymphoblastic leukaemia recurrent System Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2017-002116-14-FR
• Lead Sponsor: ovartis Pharma AG

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-08-10
• Last Update Posted: 28 February 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 140

Inclusion Criteria

Patients eligible for inclusion in this study have to meet all of the following criteria:
1. CD19 expressing B-cell Acute Lymphoblastic Leukemia
2. De novo NCI HR B-ALL who received 1st line treatment and are at MRD = 0.01% at EOC. EOC bone marrow MRD will be collected prior to screening and will be assessed by multi-parameter flow cytometry using central laboratory analysis.
3. Age 1 to 25 years at the time of screening
4. Lansky (age <16 years) or Karnofsky (age =16 years) performance status =60% at screening
5. Adequate organ function during the screening period
• Renal function based on age/gender as described in the protocol
• ALT =5 times ULN for age
• AST =5 times ULN for age
• Total bilirubin <2 mg/dL (for Gilbert’s Syndrome patients total bilirubin <4 mg/dL)
• Adequate pulmonary function defined as
- no or mild dyspnea (= Grade 1)
- oxygen saturation of > 90% on room air
• Adequate cardiac function defined as LVSF = 28% confirmed by echocardiogram or LVEF = 45% confirmed by echocardiogram or MUGA within 6 weeks of screening
6. Prior induction and consolidation chemotherapy allowed, as decribed in the protocol
7. Signed written informed consent and assent forms, if applicable, must be obtained prior to any study procedures
8. Must meet the institutional criteria to undergo leukapheresis
9. Once all other eligibility criteria are confirmed, must have a leukapheresis product of non-mobilized cells received and accepted by the manufacturing site.
NOTE: Leukapheresis product will not be shipped to or assessed for acceptance by the manufacturing site until documented confirmation of all other clinical eligibility criteria is received.

Other protocol-defined inclusion criteria may apply.
Are the trial subjects under 18? yes
Number of subjects for this age range: 125
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

Patients eligible for this study must not meet any of the following criteria:
1. M3 marrow (= 25% blasts by morphologic criteria) at the completion of first-line induction therapy
2. M2 (i.e. = 5% blasts by morphologic criteria) or M3 marrow or persistent extramedullary disease at the completion of first-line consolidation therapy. Patients with previous CNS disease are eligible if there is no active CNS involvement of leukemia at the time of enrollment.
3. Philadelphia chromosome positive (Ph+) ALL
4. Hypodiploid: less than 44 chromosomes and/or DNA index < 0.81, or other clear evidence of a hypodiploid clone
5. Prior tyrosine kinase inhibitor therapy
6. Subjects with concomitant genetic syndromes associated with bone marrow failure states: 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.
7. Patients with Burkitt’s lymphoma/leukemia (i.e. patients with mature B-ALL, leukemia with B-cell [sIg positive and kappa or lambda restricted positivity] ALL, with FAB L3 morphology and /or a MYC translocation).
8. Prior malignancy, except carcinoma in situ of the skin or cervix treated with curative intent and with no evidence of active disease.
9. Has had treatment with any prior anti-CD19 therapy
10. Treatment with any prior gene or engineered T cell therapy
11. Uncontrolled acute life threatening bacterial, viral or fungal infection (e.g. blood culture positive = 72 hours prior to tisagenlecleucel infusion)
12. Presence of active or prior hepatitis B or C as indicated by serology. Serology must be repeated, if the interval between testing at screening and tisagenlecleucel infusion exceeds 8 weeks.
13. Human Immunodeficiency Virus (HIV) positivity as indicated by serology. Serology must be repeated, if the interval between testing at screening and tisagenlecleucel infusion exceeds 8 weeks.
14. Subject had an investigational medicinal product within the last 30 days prior to screening
NOTE: Investigational therapies must not be used at any time while on study until the first relapse following CTL019 infusion.
15. If subjects are taking any of the medications defined in the protocol, their infusion (including a second infusion) must be delayed until the medications have been stopped (details according to in the protocol):
a. Medications to be stopped > 72 hours prior to tisagenlecleucel infusion: Therapeutic systemic doses of steroids.
b. Medications to be stopped at least 1 week prior to tisagenlecleucel infusion:
• 6-thioguanine, asparginase (non-pegylated), vincristine, 6-mercaptopurine, and intrathecal methotrexate
c. Medications to be stopped at least 2 weeks prior to tisagenlecleucel infusion:
• Anthracyclines and cytarabine
• Intravenous methotrexate.
• Radiotherapy: Non-CNS site of radiation
d. Medications to be stopped at least 4 weeks prior to tisagenlecleucel infusion: Pegylated-asparaginase
e. Medications/Therapy to be stopped at least 8 weeks prior to tisagenlecleucel infus

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified