Study of chemotherapy with blinatumomab and tyrosine kinase inhibitors in newly diagnosed children and young adults with Philadelphia chromosome positive B-cell acute lymphoblastic leukemia
This study involves patients with two types of B-cell Acute Lymphoblastic Leukemia, which is a cancer of the blood and bone marrow where the body makes too many immature white blood cells. The first type is called Philadelphia Chromosome Positive leukemia, which has a specific genetic change involving a chromosome abnormality called BCR::ABL1. The second type is called ABL-class Philadelphia Chromosome-Like leukemia, which behaves similarly to the first type and has genetic changes involving certain genes that include ABL1, ABL2, CSF1R, and PDGFRB. The treatment being tested combines chemotherapy with a medication called blinatumomab, which is given through a vein, along with targeted drugs called tyrosine kinase inhibitors. Patients with Philadelphia Chromosome Positive leukemia will receive dasatinib, while those with ABL-class leukemia will receive either imatinib if they have PDGFRB gene changes or dasatinib if they do not.
The purpose of this study is to measure how well this treatment combination works over a three-year period and to examine its safety in children, adolescents, and young adults with these types of leukemia. The treatment approach uses a modified chemotherapy plan that includes three cycles of blinatumomab without traditional consolidation chemotherapy, combined with continuous use of the targeted drugs. The study will track various side effects including infections, mouth sores, nerve problems, cytokine release syndrome which is a reaction from the immune system, low levels of protective antibodies in the blood, treatment delays, and deaths related to treatment.
During the study, patients will receive a combination of standard chemotherapy drugs including vincristine, steroids, and pegaspargase or calaspargase pegol, with or without an anthracycline drug. The treatment plan is designed to work differently for the two types of leukemia, with patients having already started some initial therapy before joining the study. The study will follow patients to see how many remain free from disease events over three years and will also track overall survival rates and how the treatment works based on the specific genetic changes present in each patient’s leukemia.
1Induction Therapy
This phase begins before enrollment in the study. For patients with Philadelphia Chromosome positive leukemia, induction therapy includes vincristine, a corticosteroid (a type of anti-inflammatory medication), and pegaspargase or calaspargase pegol (medications that help fight cancer cells). Some patients may also receive an anthracycline (another type of cancer-fighting medication) or other standard chemotherapy drugs.
This phase lasts no more than 14 days from the first dose of vincristine for patients with Philadelphia Chromosome positive leukemia.
For patients with ABL-class Philadelphia Chromosome-Like leukemia, induction therapy consists of multiple chemotherapy drugs given over 4 or 5 weeks.
During this phase, a tyrosine kinase inhibitor (a targeted medication that blocks specific proteins in cancer cells) may be started. This can be either imatinib or dasatinib, taken for no more than 14 days for Philadelphia Chromosome positive leukemia or no more than 35 days for ABL-class leukemia before joining the study.
2Modified Chemotherapy Backbone with Blinatumomab
After induction therapy, treatment continues with a modified chemotherapy plan based on the Berlin-Frankfurt-Münster protocol.
This phase includes three cycles of blinatumomab. Blinatumomab is an immunotherapy medication given as a continuous infusion into a vein (intravenous administration). The medication is prepared from a powder and solution, with a dose of 38.5 micrograms.
Traditional consolidation chemotherapy (an intensive phase of treatment typically used to eliminate remaining cancer cells) is not included in this treatment plan.
3Continuous Tyrosine Kinase Inhibitor Therapy
Throughout the treatment, a tyrosine kinase inhibitor is taken continuously alongside other therapies.
For patients with Philadelphia Chromosome positive leukemia, dasatinib is used continuously.
For patients with ABL-class Philadelphia Chromosome-Like leukemia, the choice of medication depends on the specific genetic characteristics: imatinib is used for those with PDGFRB gene fusions, while dasatinib is used for those without PDGFRB gene fusions.
These medications are taken orally and work by blocking specific proteins that help cancer cells grow.
4Monitoring and Safety Assessments
Throughout the treatment, regular monitoring is conducted to assess response to therapy and detect any side effects.
Safety assessments include monitoring for infections, mucositis (inflammation of the digestive tract lining), neurotoxicity (effects on the nervous system), cytokine release syndrome (an immune system reaction), and hypogammaglobulinemia (low levels of antibodies in the blood).
Any delays in treatment longer than 14 days are tracked, as well as any serious complications related to the therapy.
Blood tests are performed to check minimal residual disease (very small amounts of cancer cells that may remain after treatment), with a target of less than 0.01% at specific time points.
5Follow-up Period
After completing active treatment, a follow-up period extends up to 3 years.
During this time, regular assessments are conducted to monitor for any signs of disease recurrence and to evaluate long-term outcomes.
The study tracks event-free survival (the length of time without cancer returning or other serious complications) and overall survival over this 3-year period.
Who Can Join the Study?
Patients must be older than 365 days (1 year) and younger than 18, 22, or 46 years at the time of joining the study, depending on which study group they join.
Patients must have newly-diagnosed Ph+ B-ALL (a type of blood cancer with a specific genetic change called Philadelphia chromosome) or ABL-class Ph-like B-ALL (a type of blood cancer with genetic changes similar to Philadelphia chromosome). The cancer cells must have a protein called CD19 on their surface.
Patients must have evidence of a genetic change called BCR::ABL1 confirmed by a laboratory test before entering the study on Day 15 from the first dose of a medicine called vincristine during initial treatment.
Patients with Ph+ B-ALL must have already started initial treatment called Induction therapy, which includes medicines such as vincristine (a cancer medicine), a steroid (a medicine to reduce inflammation), pegaspargase or calaspargase pegol (enzymes that fight cancer cells), with or without anthracycline (another cancer medicine), and possibly other standard cancer medicines.
Patients with Ph+ B-ALL must not have received more than 14 days of initial treatment starting from the first dose of vincristine.
Patients with ABL-class Ph-like B-ALL must have already completed 4 or 5 weeks of initial treatment with multiple cancer medicines.
Patients may have started taking medicines called imatinib or dasatinib (medicines that target specific cancer cells) before joining the study, but should not have taken them for more than 14 days if they have Ph+ B-ALL or more than 35 days if they have ABL-class Ph-like B-ALL.
Patients must have adequate liver function, meaning their liver is working well enough to process medicines.
Patients must have adequate kidney function, meaning their kidneys are working well enough to filter waste from the blood.
Patients must have adequate heart function, meaning their heart is working well enough to pump blood properly.
Patients must have a performance status (a measure of how well they can perform daily activities) that corresponds to certain scores: ECOG score of 2 or less, or Karnofsky or Lansky performance score of 50% or higher. The Karnofsky score is used for patients older than 16 years, and the Lansky score is used for patients 16 years or younger.
Who Cannot Join the Study?
The study information provided does not list specific reasons why patients cannot participate in this clinical trial
If you are considering participation in this study, the research team will evaluate whether you meet the requirements during the screening process
General exclusion criteria typically exist for clinical trials but were not included in the available study documentation
Blinatumomab is a medicine that helps the body’s immune system find and attack leukemia cells. It works by connecting immune cells to cancer cells so they can be destroyed. In this trial, patients will receive three cycles of this medication as part of their treatment plan.
Dasatinib is a targeted therapy pill that blocks specific proteins that help leukemia cells grow and survive. It is given continuously to patients who have a specific genetic change called Philadelphia chromosome positive leukemia, and to some patients with ABL-class Philadelphia chromosome-like leukemia who do not have PDGFRB gene changes.
Imatinib is a targeted therapy pill that blocks specific proteins that help cancer cells grow. It is given continuously to patients with ABL-class Philadelphia chromosome-like leukemia who have specific genetic changes involving the PDGFRB gene.
Chemotherapy is a treatment that uses strong medicines to kill cancer cells or stop them from growing. In this trial, patients will receive a modified combination of chemotherapy drugs based on a treatment plan called Berlin-Frankfurt-Münster, but without the traditional consolidation chemotherapy phase.
Philadelphia Chromosome Positive B-cell Acute Lymphoblastic Leukemia – This is a type of blood cancer that affects white blood cells called B-cells. It occurs when a specific genetic abnormality called the Philadelphia chromosome forms in the bone marrow cells. This chromosome results from an abnormal exchange of genetic material between chromosomes 9 and 22, creating a fusion gene called BCR-ABL1. The disease causes the bone marrow to produce large numbers of immature white blood cells that do not function properly. These abnormal cells multiply rapidly and crowd out healthy blood cells in the bone marrow and bloodstream. The condition progresses quickly and affects the body’s ability to fight infections and produce normal blood cells.
ABL-class Philadelphia Chromosome-Like B-cell Acute Lymphoblastic Leukemia – This is a subtype of blood cancer that affects B-cells and shares similar characteristics with Philadelphia chromosome positive leukemia but has different genetic changes. Instead of the BCR-ABL1 fusion, it involves other genetic abnormalities in ABL-class genes that affect similar cellular pathways. The disease can involve various gene fusions, including those affecting the PDGFRB gene and other ABL-class genes. Like other forms of acute lymphoblastic leukemia, it causes the bone marrow to produce excessive numbers of immature white blood cells. These abnormal cells accumulate in the bone marrow and blood, interfering with the production of normal blood cells. The condition progresses rapidly and impairs the immune system’s ability to function properly.
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