None listed
Conditions
Brief summary
Brief description of the study purpose The CAPITALL Study aims to determine whether introducing blinatumomab earlier in the treatment of children and adolescents with B-cell acute lymphoblastic leukaemia (B-ALL) can achieve similar levels of leukaemia clearance and cure, while potentially reducing the overall treatment burden compared with the standard chemotherapy regime. Who is it for? You may be eligible for this study if you are under 18 years of age who are newly diagnosed with B-cell acute lymphoblastic leukaemia (B-ALL), including certain infant cases without KMT2A rearrangement. Study details All those who are eligible will be treated according to their risk group (standard, medium, or high risk) using established clinical, genetic, and molecular criteria. Most participants (excluding standard-risk patients) will receive blinatumomab following initial induction therapy. Blinatumomab is an approved medication given as a continuous intravenous infusion over 28 days, with 1–3 treatment blocks depending on the participant’s treatment plan. This is a single-arm study, meaning all participants receive study treatment, and there is no randomisation. Study results will be compared to historical patient data from previous trials and standard treatment regimens. Participants will undergo regular assessments, including blood tests and molecular testing (e.g. minimal residual disease testing), to measure how effectively the treatment clears leukaemia cells. It is hoped that the results from this study will help demonstrate whether earlier use of blinatumomab can maintain treatment effectiveness while reducing treatment intensity, potentially improving outcomes and quality of life for children with B-ALL.
Interventions
The purpose of this study is to evaluate the effects of introducing blinatumomab earlier in treatment for paediatric patients with acute lymphoblastic leukaemia (ALL), compared with the current standard treatment schedule. The study will compare leukaemia clearance, treatment outcomes, and overall treatment burden between the two treatment approaches.
Patients will be stratified into risk groups as with standard treatment (standard, medium and high risk). Patients are stratified using a clinic
The purpose of this study is to evaluate the effects of introducing blinatumomab earlier in treatment for paediatric patients with acute lymphoblastic leukaemia (ALL), compared with the current standard treatment schedule. The study will compare leukaemia clearance, treatment outcomes, and overall treatment burden between the two treatment approaches. Patients will be stratified into risk groups as with standard treatment (standard, medium and high risk). Patients are stratified using a clinical, genetic and molecular response criteria at diagnosis and at specified timepoints throughout treatment. This is not a randomised study and most patients will receive blinatumomab during their treatment, not including standard risk patients (as per standard treatment). Patients on the CAPITALL study will have complete assessments and have their medical records reviewed. We will compare the results of patients treated on CAPITALL with those of patients recently treated at our hospitals using the standard treatment regime. This trial uses only approved drugs and will have a focus on blinatumomab. Blinatumomab is given in blocks (1-3) depending on the patients risk stratification and determined treatment plan. Blinatumomab Dose: 15mcg/m2/day (maximum dose 28 mcg/day) Blinatumomab Duration: 28 days Blinatumomab Mode: Continuous 28 day Intravenous Infusion On this study patients will receive the following treatment blocks based on their risk stratification in the order listed below: Standard Risk: Induction, Consolidation, Protocol M, Protocol III and Maintenance. This is the exact course of treatment as per standard of care. Medium Risk: Induction, Blinatumomab Block 1, Consolidation, Protocol M, Protocol II, Blinatumomab Block 2 and Maintenance. High Risk: Induction, Blinatumomab Block 1, Consolidation, High Risk Course 1, then either High Risk Blinatumomab Blocks 2 & 3 or alternatively High Risk Course 2 & 3 (for patients who don’t respond as well to Blinatumomab), Protocol III and Maintenance. All patients regardless of risk stratification will be on treatment for at least 2 years from the start of Induction.
Sponsors
University of New South Wales - Sydney
Study design
Allocation
Non-randomised trial
Intervention model
Other
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
12 Months to 18 Years
Healthy volunteers
No
Inclusion criteria
Each patient must meet all of the following criteria to be enrolled in this trial: • Patient must provide a signed and dated informed consent form or have a legally acceptable representative capable of understanding the informed consent document and providing consent on the patient’s behalf. • Patients must be newly diagnosed with B-cell acute lymphoblastic leukaemia or newly diagnosed non-KMT2A rearranged infant (<12month old) ALL. • Age <18 years on the day of diagnosis. • Females of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to initiation of treatment, agree to use adequate contraception during the study and for 12 months following completion of anti-leukaemic therapy.
Exclusion criteria
Patients meeting any of the following criteria will be excluded from the trial: • Patients with Ph+ (BCR-ABL1 or t(9;22) positive) ALL. • Patients with CD19 -negative precursor B ALL at diagnosis. • Patients with Mixed phenotype acute leukaemia (MPAL), undifferentiated leukaemia or biphenotypic leukaemia. • Infants <12mo with KMT2A rearranged ALL. • Patients with B cell lymphoblastic lymphoma. • Pre-treatment with ?1mg/kg/day prednisone equivalent for more than 2 weeks during the last month before diagnosis. • Pre-treatment with other cytotoxic agents or following another protocol. • Patients with an underlying disease, condition or circumstance that will interfere with ability to deliver treatment according to the protocol. • Pregnant or nursing (lactating) females. • Live vaccine immunisation within 2 weeks before start of protocol treatment. • Sexually active patients not willing to use highly effective contraceptive method until 12 months after the end of anti-leukaemic therapy. The following additional exclusion criteria apply to non-SR patients who would be ineligible for blinatumomab treatment and thus taken off study: • Patients with significant CNS pathology that would preclude treatment with blinatumomab, including a history of severe neurologic disorder or autoimmune disease with CNS involvement. • Evidence of active CNS ALL at time of blinatumomab. Patients with CNS disease present at diagnosis which has cleared remain eligible. • Patients with uncontrolled HIV infection. • Known hypersensitivity to immunoglobulins. Patients who are not enrolled on treatment prior to Day 12 of induction treatment will not be eligible.
Outcome results
None listed