Subcutaneous Blinatumomab Plus Ponatinib for BCR-ABL+ B-ALL

NCT07301424 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: CLSG-ALL-2
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Acute Lymphoblastic Leukemia (ALL) Philadelphia Chromosome-positive (Ph+); BCR-ABL Positive Acute Lymphoblastic Leukemia

Keywords

Blinatumomab; Ponatinib; BiTE antibody; Acute lymphoblastic leukemia; BCR-ABL positive acute lymphoblastic leukemia

Outcome Measures

Primary Outcomes (2)

• • 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.

  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.

  At end of cycle 2 of Blinatumomab (each cycle being 28 days).

Secondary Outcomes (9)

• Complete response rate

  Determined at the end of the 70 day induction phase

• Patient and caregiver experience

  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

  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)

  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)

  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.

Other Outcomes (1)

• Exploratory: comparison of different MRD outcomes

  After the completion of cycle 2 of blinatumomab (each cycle being 28 days).

Study Arms (1)

Treatment with subcutaneous blinatumomab plus ponatinib

EXPERIMENTAL

Drug: Treatment with blinatumomab given subcutaneously.

Interventions

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.

Treatment with subcutaneous blinatumomab plus ponatinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• \. Greater than or equal to 5% blasts in the BM.
• \. Performance status ≤2 (ECOG Scale, see Appendix IV)
• \. Adequate organ function: 5.1.5.1 Hepatic:
• 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%

You may not qualify if:

• 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:
• 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
• 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

Sponsors & Collaborators

• Amgen: collaborator
• University of Alberta: lead

Study Sites (1)

University of Alberta

Edmonton, Alberta, T6G 2G3, Canada

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Therapeutics

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Joseph Brandwein, MD, FRCPC

CONTACT

780-407-5184; jbrandwe@ualberta.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2025
• First Posted: December 24, 2025
• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 1, 2031
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Time Frame: These data will be made available once the primary outcome data on all subjects are available, and after results have been reported and published.
• Access Criteria: Academic researchers may be provided with the data on request only.

Locations

CA (1)