Blinatumomab + Asciminib for Philadelphia Chromosome Positive Leukemia

Overseen By Nicholas Short, MD

Age: 18+

Sex: Any

Trial Phase: Phase 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)

Prior Safety Data This treatment has passed at least one previous human trial

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

Trial Summary

What is the purpose of this trial?

To learn if the combination of blinatumomab and asciminib can help to control Ph+ ALL.

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.

What data supports the effectiveness of the drug Asciminib for Philadelphia Chromosome Positive Leukemia?

Asciminib has shown effectiveness in treating chronic myeloid leukemia (CML) in patients who have not responded to at least two other treatments, with better results and fewer side effects compared to another drug, bosutinib. It is particularly effective for patients with specific mutations that make other treatments less effective. ^{1 2 3 4 5}

Is the combination of Blinatumomab and Asciminib safe for humans?

Asciminib has been studied in patients with chronic myeloid leukemia and has shown a generally favorable safety profile. Common side effects include increased pancreatic enzymes, low platelet counts, high blood pressure, and low white blood cell counts. Most side effects occurred in the first year of treatment, and the likelihood of new side effects decreased over time. ^{2 4 6 7 8}

How is the drug combination of Blinatumomab and Asciminib unique for treating Philadelphia Chromosome Positive Leukemia?

This drug combination is unique because Asciminib is a novel type of drug that specifically targets a unique part of the BCR-ABL1 protein, which is often resistant to other treatments, while Blinatumomab helps the immune system attack cancer cells. Asciminib's ability to target the myristoyl pocket of the BCR-ABL1 protein makes it effective against mutations that other drugs can't treat. ^{1 2 4 5 7}

Research Team

Nicholas Short

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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 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]

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 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]

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 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 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]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Asciminib: First Approval. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Asciminib monotherapy for newly diagnosed chronic myeloid leukemia in chronic phase: the ASC4FIRST phase III trial. [2023]

3. England pubmed.ncbi.nlm.nih.gov

An evaluation of asciminib for patients with chronic myeloid leukemia previously treated with ≥2 tyrosine kinase inhibitors. [2022]

4. England 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. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Asciminib for chronic myeloid leukaemia: Next questions. [2022]

6. England 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. [2023]

7. England 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. [2023]

8. Japan 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]. [2023]