Acute Lymphoblastic Leukemia (ALL) Philadelphia Chromosome-positive (Ph+)Phase 2NCT07301424
Subcutaneous Blinatumomab Plus Ponatinib for BCR-ABL+ B-ALL
A Phase 2 study testing Treatment with blinatumomab given subcutaneously. in people with Acute Lymphoblastic Leukemia (ALL) Philadelphia Chromosome-positive (Ph+) and BCR-ABL Positive Acute Lymphoblastic Leukemia, run by University of Alberta at 1 site in Canada.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Lymphoblastic Leukemia (ALL) Philadelphia Chromosome-positive (Ph+), BCR-ABL Positive Acute Lymphoblastic Leukemia
- What is being tested?
- Treatment with blinatumomab given subcutaneously.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteCanada
- Study dates
- 2 Jan 2027to Dec 2031
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 3. Greater than or equal to 5% blasts in the BM.
- 4. Performance status ≤2 (ECOG Scale, see Appendix IV)
- 5. Adequate organ function: 5.1.5.1 Hepatic:
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- Adequate liver function as defined by the following criteria (unless the increased values are judged to be leukemia disease related):
- Total serum bilirubin less than 2 x upper limit of normal (ULN), unless due to Gilbert's syndrome or Meulengracht disease Alanine aminotransferase (ALT) less than 3 x ULN Aspartate aminotransferase (AST) less than 3 x ULN 5.1.5.2 Pancreatic:
- Serum lipase less than 2 x ULN 5.1.5.3 Renal:
- Estimated Creatinine clearance ≥ 40 mL/min 5.1.5.4 Cardiac:
- Left ventricular ejection fraction > 40%
Who cannot join
- Uncontrolled infection
- Known infection with human immunodeficiency virus (HIV) or chronic infection with hepatitis B virus or hepatitis C virus
- Presence of cardiovascular disease of clinical relevance within the past 3 months. This includes:
- 5.2.3.1 Unstable angina 5.2.3.2 Myocardial infarction 5.2.3.3 Transient ischemic attack or stroke 5.2.3.4 Peripheral vascular infarction, claudication and/or revascularization 5.2.3.5 Symptomatic congestive heart failure 5.2.3.6 Clinically significant significant atrial/ventricular tachyarrhythmias 5.2.3.7 Venous thromboembolic event requiring systemic anticoagulation
- Please consult the sponsor if there are specific concerns outside of these criteria
- Uncontrolled hypertension
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- History or presence of clinically relevant CNS pathology or event.
- This may include, for example:
- epilepsy, childhood or adult seizure, paresis, aphasia, stroke, severe brain injuries, dementia, Parkinson's disease, cerebellar disease, organic brain syndrome or psychosis.
- Before excluding a potential subject, please consult the sponsor.
- Any other concurrent disease or medical condition that could be exacerbated by the treatment or would seriously complicate compliance with the protocol.
- History of malignancy other than ALL within 3 years prior to start of protocol-specified therapy except for:
- malignancy treated with curative intent and with no known active disease present for 3 years before enrollment, and felt to be at low risk for recurrence by the treating physician
- adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- adequately treated cervical carcinoma in situ without evidence of disease
- adequately treated breast ductal carcinoma in situ without evidence of disease
- prostatic intraepithelial neoplasia without evidence of prostate cancer
- Prior hematologic malignancy and/or alloSCT; this includes known CML
- Concurrent or prior (within 30 days) treatment with another investigational agent or study drug
- Female subject is pregnant or breastfeeding or planning to become pregnant breastfeed during treatment, and for an additional 4 months after the last dose of protocol-specified therapy
- Inability to swallow or absorb tablets
- Subject considered unsuitable for study for any other reason in the physician's best judgement. Before excluding a potential subject, please consult the sponsor.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site
University of Alberta
Edmonton, Alberta, T6G 2G3
Joseph Brandwein, MD, FRCPC, 7804075184, jbrandwe@ualberta.ca
About this study
Official title: Phase II Study of Subcutaneous Blinatumomab Plus Ponatinib for BCR-ABL Positive B-Cell Acute Lymphoblastic Leukemia
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.
Read more
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.
Read the detailed description
This Phase II clinical trial will evaluate with efficacy and tolerance of subcutaneous (sc) blinatumomab (blina) combined with ponatinib for previously untreated patients with BCR-ABL (Ph) positive B-cell acute lymphoblastic leukemia (ALL).
Participants will, after a brief steroid pre-phase, receive induction therapy with ponatinib 30 mg/day x 70 days, with prednisone for the first month. They will then receive 5 cycles of consolidation therapy with sc blina. The first cycle will consist of blina 250 mcg sc daily x 7 days, then 500 mcg sc 3x/week x 3 weeks. Cycles 2-5 will consist of blina 500 mcg sc 3x/week x 4 weeks. There will be a 2 week break in between each consolidation cycle. Ponatinib will continue at 30 mg daily through the end of consolidation. Participants will then receive maintenance therapy with ponatinib 15 mg/day until 5 years from the start of induction.
Intrathecal chemotherapy will be administered for a total of 15 doses; this will include 7 doses during induction, 1 dose in between each consolidation cycle, and 4 during maintenance.
Efficacy will be determined by bone marrow assessments for MRD at various timepoints. The primary endpoint is the measurable residual disease (MRD) response after the end of consolidation cycle 2, by both BCR-ABL PCR (MRD4 or greater) and by IgR (MRD negativity by Clonoseq[R]). The CR rate, MRD response duration, RFS and OS will also be assessed.
Toxicity will be evaluated throughout the study and graded using CTCAE V5. Quality of life will be assessed at various timepoints using QLQ-C30.
- Conditions
- Acute Lymphoblastic Leukemia (ALL) Philadelphia Chromosome-positive (Ph+), BCR-ABL Positive Acute Lymphoblastic Leukemia
- Being tested
- Treatment with blinatumomab given subcutaneously.
- Keywords
- Blinatumomab, Ponatinib, BiTE antibody, Acute lymphoblastic leukemia, BCR-ABL positive acute lymphoblastic leukemia
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Treatment with blinatumomab given subcutaneously.Drug
Previous 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.
| Study group | Role | What they receive |
|---|---|---|
| Treatment with subcutaneous blinatumomab plus ponatinib | Experimental | Not described Receives: Drug: Treatment with blinatumomab given subcutaneously. |
What is being measured
The primary outcome is the main question the study is designed to answer.
• 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.
Measured: At end of cycle 2 of blinatumomab (each cycle is 28 days).
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.
Measured: At end of cycle 2 of Blinatumomab (each cycle being 28 days).
Secondary outcomes (9)
Complete response rate
Complete response rate (CR and CRh) of ponatinib + prednisone
Measured: Determined at the end of the 70 day induction phase
Patient and caregiver experience
EORTC QLQ-C30 scores
Measured: At screening, end of induction (Day 70), end of cycles 2 and 5 of blinatumomab, and one year after start of maintenance therapy with ponatinib.
Molecular response duration
The duration of MR4 by PCR and CMR by Clonoseq will be determined in follow-up bone marrow assessments.
Measured: From the time of documented remission at Day 70 of induction, until the date of first documented molecular progression, assessed up to 5 years from the start of treatment.
Relapse-free survival (RFS)
Time from primary outcome to molecular disease progression.
Measured: From the date of documented remission at day 70 until the date of first documented relapse or date of death from any cause, whichever came first, assessed up to 5 years from the start of treatment.
Overall survival (OS)
Time from start of treatment until death form any cause or last follow-up.
Measured: From the date of enrollment until the date of death from any cause or last follow-up, assessed up to 5 years from the start of treatment.
Safety and tolerability
Safety and tolerability of the ponatinib plus blinatumomab combination, based on TEAE's, graded by CTCAE V5, as well as by CRS and ICANS grading.
Measured: From the start of study treatment through the completion of study treatment at 5 years.
Prognostic factors for remission
Correlation of primary efficacy endpoints (MR4, CMR) with diagnostic NGS, IKZFplus genotype, age and baseline WBC
Measured: At the primary endpoint at the end of cycle 2 of blinatumomab (each cycle being 28 days).
Prognostic factors for relapse-free survival
Correlation of RFS with diagnostic NGS, IKZFplus genotype, age and baseline WBC
Measured: From date of documented remission at day 70 of induction, until the date of relapse or date of death from any cause, whichever came first, assessed up to 5 years.
Prognostic factors for overall survival
Correlation of OS with diagnostic NGS, IKZFplus genotype, age and baseline WBC
Measured: From date of enrollment until the date of death from any cause or last follow-up, assessed up to 5 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2025
- Study start2 Jan 2027 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lymphoblastic Leukemia (ALL) Philadelphia Chromosome-positive (Ph+)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Alberta
- Sponsor type
- University, hospital or other
- Collaborators
- Amgen
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07301424
- Sponsor's protocol ID
- CLSG-ALL-2
- Status last verified
- Aug 2026
- First submitted
- 12 Dec 2025
- Last updated
- 12 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual participant data (IPD) regarding baseline molecular data and molecular response data collected in this study will be made available to other researchers on request.