B-cell acute lymphoblastic leukemia (B-ALL) is an aggressive blood cancer; about 30% of B-ALL cases in adults have a mutation called BCR-ABL that drives the disease.
Blinatumomab is an antibody drug that targets B-ALL cells and helps the immune system to kill them. It is usually given intravenously, but a newer formulation can be given under the skin. Ponatinib is a drug, taken by mouth, that targets and kills leukemia cells that have the BCR-ABL mutation.
The goal of this clinical trial is to test the effectiveness of treating patients with BCR-ABL positive B-ALL with blinatumomab given subcutaneously (under the skin) combined with ponatinib tablets. The study will also evaluate what side effects occur using this combination.
Participants will first receive ponatinib tablets for 70 days, along with prednisone for the first month. This will be followed by blinatumomab injections 3 times per week for 4 weeks, repeated for 5 treatment cycles, along with ponatinib. Participants will then continue ponatinib tablets alone for 5 years from the start of treatment.
During treatment, participants will undergo regular blood and bone marrow tests to see how well the treatment is working, and to check for side effects. The effect of this treatments on their quality of life will also be evaluated.
Ph positive [either t(9;22) and/or BCR-ABL1 positive] ALL, CD19 positive
Age ≥18 years at time of informed consent
No prior induction treatment for ALL. A brief corticosteroid pre-phase (< 1 week), or hydroxyurea for cytoreduction or symptom control is permitted.
Left ventricular ejection fraction > 40%
Uncontrolled infection
Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus
Uncontrolled hypertension
History or presence of clinically relevant CNS pathology or event.
Single group
Treatment with blinatumomab given subcutaneously.
DrugPrevious studies have used intravenous blinatumomab combined with a TKI (ponatinib or dasatinib) for patients with BCR-ABL positive B-ALL. This study is using subcutaneous blinatumomab combined with ponatinib for previously untreated patients with this disease.
• MR4 rate for BCR-ABL1 by PCR after 2 cycles of blinatumomab
After 2 cycles of blinatumomab, the bone marrow will be tested for MRD by PCR for BCR-ABL. The rate of MRD4 (MRD\<10\[-4\]) at this timepoint will constitute a primary outcome.
Complete molecular response (CMR) by IgR (Clonoseq[R]) after 2 cycles of blinatumomab.
After 2 cycles of Blinatumomab the marrow will be tested for MRD by Clonoseq. The rate of MRD negativity by IgR will constitute a primary outcome.
Complete response rate
Complete response rate (CR and CRh) of ponatinib + prednisone
Patient and caregiver experience
EORTC QLQ-C30 scores
Molecular response duration
The duration of MR4 by PCR and CMR by Clonoseq will be determined in follow-up bone marrow assessments.
Relapse-free survival (RFS)
Time from primary outcome to molecular disease progression.
Exploratory: comparison of different MRD outcomes
Concordance between MRD results in bone marrow by BCR-ABL PCR vs IgR vs flow cytometry
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University of Alberta
Lead sponsor
Amgen
Collaborator
This trial is not recruiting at the moment. You can still explore other options:
