Blinatumomab + Asciminib for Philadelphia Chromosome Positive Leukemia

Overseen By Nicholas Short, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Investigational agents

Disqualifiers: Active infection, Secondary malignancy, Cardiac failure, CNS pathology, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 5 months

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two treatments, blinatumomab and asciminib, to determine their effectiveness in controlling Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia (Ph+ ALL), a type of blood cancer. Participants will initially receive both treatments, followed by asciminib alone if it remains beneficial. The trial seeks individuals with Ph+ ALL, particularly those who have tried other unsuccessful treatments or have untreated or minimally treated conditions. Participants should have this type of leukemia and not be suitable for intensive chemotherapy.

As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group. It offers a chance to contribute to groundbreaking advancements in leukemia treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, if you have taken investigational antileukemic or chemotherapy agents in the last 7 days, you may need to wait until you recover from any side effects before joining the study.

Is there any evidence suggesting that the combination of blinatumomab and asciminib is likely to be safe for humans?

Research shows that the combination of blinatumomab and asciminib is being tested for safety in people with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Earlier studies have used these drugs with others like dasatinib, suggesting that asciminib with blinatumomab can be safe for patients with Ph+ leukemia.

Blinatumomab is already known for treating certain types of leukemia and has been tested for safety in many patients. Asciminib is newer but has shown promising safety results when combined with other treatments for similar conditions. So far, no major safety issues have emerged in these early studies.

This trial is in an early stage (Phase 1/Phase 2), meaning researchers are still assessing how well this combination is tolerated. This phase ensures a treatment is safe before larger studies are conducted. The data appears promising so far, but more research is needed for confirmation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Blinatumomab and Asciminib for treating Philadelphia Chromosome Positive Leukemia because it offers a unique approach compared to standard treatments like tyrosine kinase inhibitors. Blinatumomab is a bispecific T-cell engager, which means it helps the body's immune system target and destroy cancer cells more effectively. Asciminib, on the other hand, uses a novel mechanism by specifically inhibiting the BCR-ABL1 fusion protein, a key player in this type of leukemia. This dual-action strategy not only targets the cancer more precisely but also has the potential to overcome resistance seen with traditional treatments.

What evidence suggests that the combination of blinatumomab and asciminib could be effective for Ph+ ALL?

This trial will evaluate the combination of blinatumomab and asciminib for treating Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Research shows that these two drugs together may help treat this type of leukemia. Blinatumomab has been studied before and effectively targets and destroys cancer cells in this leukemia. Asciminib focuses on a specific protein that aids cancer growth, and earlier studies suggest it could be useful, especially when the disease returns or doesn't respond to other treatments. Initial results indicate that combining these drugs might enhance treatment effectiveness by using their different methods of attacking cancer cells. This approach aims to improve outcomes for patients with this challenging form of leukemia. ^{1 2 3 6 7}

Who Is on the Research Team?

Nicholas Short

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

This trial is for patients with a type of leukemia known as Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL). Specific eligibility criteria are not provided, but typically participants would need to meet certain health standards and may be required to have tried other treatments first.

Inclusion Criteria

I have been diagnosed with a specific condition.

My pancreas works well.

My heart is healthy according to my doctor.

Exclusion Criteria

I do not have severe heart failure.

Participants must not have prolonged QTc interval on pre-entry electrocardiogram (> 470 msec) unless corrected after electrolyte replacement or approved by cardiologist

I do not have any significant brain or nervous system conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 5 cycles of blinatumomab and asciminib, followed by asciminib alone

5 months

Continuous infusion and oral administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants continue to receive asciminib alone for as long as it benefits them

As long as beneficial

What Are the Treatments Tested in This Trial?

Interventions

• Asciminib
• Blinatumomab

Trial Overview The study is testing the effectiveness of combining two drugs, Blinatumomab and Asciminib, in treating Ph+ ALL. It's a Phase II trial, which means it focuses on the treatment's efficacy and side effects in a larger group than initial trials.

How Is the Trial Designed?

Group I: Blinatumomab + Asciminib Experimental Treatment 2 Interventions

Participants found to be eligible to take part in this study will receive 5 cycles of blinatumomab and asciminib, followed by asciminib alone for as long as it benefits the participant. Participants will receive blinatumomab as a continuous (non-stop) infusion on Days 4-31 of Cycle 1 and on Days 1-28 of Cycles 2-5. Participants will take asciminib by mouth 2 times every day during this study.

Asciminib is already approved in United States, European Union for the following indications:

Approved in United States as Scemblix for:

• Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) in adults previously treated with ≥2 tyrosine kinase inhibitors (TKIs)
• Ph+ CML in CP with the T315I mutation
• newly diagnosed Ph+ CML in CP

Approved in European Union as Scemblix for:

• Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP) in adults previously treated with ≥2 tyrosine kinase inhibitors (TKIs)
• Ph+ CML in CP with the T315I mutation

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Novartis Pharmaceuticals

Industry Sponsor

Trials

2,963

Recruited

4,275,000+

Founded

1996

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Gleevec, Cosentyx, Entresto, Kisqali

Dr. Vas Narasimhan

Novartis Pharmaceuticals

Chief Executive Officer since 2018

MD from Harvard Medical School

Dr. Shreeram Aradhye

Novartis Pharmaceuticals

Chief Medical Officer since 2021

MD

Published Research Related to This Trial

In a phase 1 trial involving 115 patients with chronic myeloid leukemia (CML-CP), asciminib demonstrated long-term efficacy, with 61.3% of patients achieving a major molecular response (MMR) after approximately 4 years of treatment.

While asciminib was generally well-tolerated, common grade ≥3 adverse events included increased pancreatic enzymes (22.6%) and thrombocytopenia (13.9%), but most adverse events occurred in the first year, indicating a manageable safety profile over time.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib monotherapy in patients with CML-CP without BCR::ABL1 T315I mutations treated with at least two prior TKIs: 4-year phase 1 safety and efficacy results. Mauro, MJ., Hughes, TP., Kim, DW., et al.[2023]

Asciminib hydrochloride, the first tyrosine kinase inhibitor targeting the ABL myristoyl pocket, was approved for chronic myeloid leukemia (CML) patients who are resistant or intolerant to prior therapies, showing significant antitumor effects in both lab and animal studies.

In a phase III study, asciminib demonstrated superior efficacy compared to bosutinib in achieving a major molecular response at week 24 for patients with chronic phase CML previously treated with multiple TKIs, with the most common side effect being thrombocytopenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacological and clinical profile of asciminib hydrochloride, a novel first-in-class tyrosine kinase inhibitor specifically targeting ABL myristoyl pocket]. Chung, J., Ariyoshi, T., Yoneda, T., et al.[2023]

Asciminib (Scemblix®) is an innovative oral medication that selectively inhibits the BCR-ABL1 tyrosine kinase, specifically targeting the myristoyl pocket, making it effective against certain mutations like T315I that resist traditional treatments.

In October 2021, asciminib received accelerated approval for adults with Philadelphia chromosome-positive chronic myeloid leukaemia (CML) who have previously been treated with at least two other tyrosine kinase inhibitors, highlighting its efficacy in difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib: First Approval. Deeks, ED.[2022]

Asciminib is a newly approved BCR-ABL1 inhibitor specifically targeting the ABL myristoyl pocket, offering a potent treatment option for chronic myeloid leukaemia (CML) patients who have not responded to at least two prior therapies or have the T315I mutation.

The drug is noted for its high potency and good tolerability due to limited off-target effects, but further research is needed to determine its optimal use compared to other tyrosine kinase inhibitors like ponatinib, especially in first- and second-line treatments and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib for chronic myeloid leukaemia: Next questions. Shanmuganathan, N., Hughes, TP.[2022]

Asciminib is an effective treatment for chronic myeloid leukemia (CML) in patients who have previously been treated with at least two tyrosine kinase inhibitors, showing a major molecular response (MMR) rate of 25.5% compared to 13.2% in the control group during the phase III ASCEMBL study.

While asciminib is generally effective, it can cause significant side effects, including thrombocytopenia, neutropenia, and increased pancreatic enzymes, with at least 5% of patients experiencing these adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The EMA Assessment of Asciminib for the Treatment of Adult Patients With Philadelphia Chromosome-Positive Chronic Myeloid Leukemia in Chronic Phase Who Were Previously Treated With at Least Two Tyrosine Kinase Inhibitors. Tesileanu, CMS., Michaleas, S., Gonzalo Ruiz, R., et al.[2023]

Asciminib, a new treatment for chronic myeloid leukemia (CML), showed superior efficacy compared to bosutinib, with a major molecular response rate of 37.6% versus 15.8% after 96 weeks in patients who had previously been treated with two or more tyrosine kinase inhibitors.

Patients taking asciminib experienced fewer severe adverse events and were more likely to continue treatment without discontinuation, indicating better safety and tolerability compared to bosutinib.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib vs bosutinib in chronic-phase chronic myeloid leukemia previously treated with at least two tyrosine kinase inhibitors: longer-term follow-up of ASCEMBL. Hochhaus, A., Réa, D., Boquimpani, C., et al.[2023]

Asciminib is the first drug that specifically targets the ABL myristoyl pocket, showing promising efficacy and safety in patients with chronic myeloid leukemia (CML) who have previously been treated with multiple tyrosine kinase inhibitors (TKIs).

The ongoing phase III trial (ASC4FIRST) is comparing asciminib to standard TKIs in newly diagnosed CML patients, with the primary goal of achieving a major molecular response by week 48, highlighting its potential as a new treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Asciminib monotherapy for newly diagnosed chronic myeloid leukemia in chronic phase: the ASC4FIRST phase III trial. Cortes, JE., Hochhaus, A., Takahashi, N., et al.[2023]

Asciminib is a first-in-class BCR::ABL1 inhibitor that specifically targets the ABL myristoyl pocket, showing promise in overcoming resistance or intolerance to existing tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML) patients.

Clinical data indicate that asciminib has considerable efficacy in CML patients who have failed at least two prior TKIs, with a favorable safety profile and low cross-intolerance with other TKIs, making it a significant advancement in CML treatment options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of asciminib for patients with chronic myeloid leukemia previously treated with ≥2 tyrosine kinase inhibitors. García-Gutiérrez, V., Hernandez-Boluda, JC.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06308588?cond=Chromosome%20translocation&viewType=Table&rank=7

Phase I/II Study of the Combination of Blinatumomab and ... Phase I/​II Study of the Combination of Blinatumomab and Asciminib in Patients With Philadelphia Chromosome -Positive Acute Lymphoblastic Leukemia.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.6509

A phase I study of asciminib in combination with dasatinib ... Our phase 1 study (NCT03595917) confirmed the safety and preliminary efficacy of DAS 140 mg/day(d) and ASC 80 mg/d (Luskin Blood 2024).

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11665558/

Ph+ ALL: new approaches for upfront therapy - PMC Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial.

4. ashpublications.org ashpublications.org/bloodadvances/article/9/18/4580/546039/Asciminib-for-relapsed-or-refractory-Philadelphia

Asciminib for relapsed or refractory Philadelphia chromosome ... Asciminib for relapsed or refractory Philadelphia chromosome–positive acute lymphoblastic leukemia Open Access ; High dose chemotherapy, 2 (4.9) ; Low dose ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06773936

Study Details | NCT06773936 | Adding Asciminib to Usual ... Patients will receive Blinatumomab every day for 28 days and Dasatinib every day for 42 days. After weeks of treatment, patients are tested and if there are no ...

6. uchicagomedicine.org uchicagomedicine.org/find-a-clinical-trial/clinical-trial/irb200455

CLINICAL TRIAL / NCT03595917 The reason for this study is to learn whether ABL001 is safe and can have possible benefits for people with Ph+ ALL who are also being treated with dasatinib ...

7. haematologica.org haematologica.org/article/view/12134

Asciminib for Philadelphia chromosome-positive leukemias The safety data ... Ponatinib efficacy and safety in Philadelphia chromosome-positive leukemia: final 5-year results of the phase 2 PACE trial.