Blinatumomab + TKI for Acute Lymphoblastic Leukemia

Recruiting at 2 trial locations

Overseen By Jae Park, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Memorial Sloan Kettering Cancer Center

Must be taking: Corticosteroids, TKI therapy

Must not be taking: T-cell suppressive therapy

Disqualifiers: Philadelphia chromosome-negative ALL, Heart disease, 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

17 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test whether blinatumomab in combination with TKI therapy (such as dasatinib) is an effective treatment for people with Ph+ ALL. Researchers want to improve the response to standard-of-care treatment of corticosteroids + TKI therapy by adding the study drug, blinatumomab.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, it mentions that you should not have ongoing needs for certain medications like systemic T-cell suppressive therapy. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Blinatumomab + TKI for treating Acute Lymphoblastic Leukemia?

Blinatumomab has shown promise in treating certain types of acute lymphoblastic leukemia (ALL), with studies indicating it can lead to remission in some patients. Additionally, combining Blinatumomab with a TKI has shown effectiveness in a few cases of a specific type of ALL, suggesting potential benefits of this combination. ^{1 2 3 4 5}

Is the combination of Blinatumomab and TKI safe for treating acute lymphoblastic leukemia?

Blinatumomab (also known as Blincyto) has been used in treating acute lymphoblastic leukemia (ALL) and has shown some effectiveness, but it can cause serious side effects in some patients. These side effects can be severe, so it's important to discuss potential risks with your doctor. ^{1 4 6 7 8}

What makes the drug Blinatumomab + TKI unique for treating acute lymphoblastic leukemia?

Blinatumomab is a unique drug because it is a bispecific T-cell engager, which means it helps the body's immune cells target and destroy cancer cells. When combined with a tyrosine kinase inhibitor (TKI) like Dasatinib, it offers a novel approach for treating certain types of acute lymphoblastic leukemia, especially in patients who have relapsed or have specific genetic markers. ^{1 2 3 6 7}

Research Team

Mark Geyer, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Eligibility Criteria

Adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) who haven't had treatment beyond corticosteroids or certain chemotherapies. Participants must be able to consent, have acceptable liver function and organ health, agree to use birth control during and after the study, and have a performance status indicating they are relatively active.

Inclusion Criteria

Able to give informed consent

I can take care of myself and perform daily activities.

Histology confirmed by enrolling institution

Exclusion Criteria

My leukemia is not caused by the Philadelphia chromosome.

I have an active hepatitis C infection.

My heart condition meets specific health criteria.

Timeline

Pre-phase

Patients may receive corticosteroids and/or hydroxyurea prior to beginning induction therapy

7 days

Induction Therapy

Induction therapy consists of dexamethasone in combination with TKI, with CNS prophylaxis and bone marrow evaluations

6 weeks

Consolidation Therapy

Patients in complete response proceed to consolidation therapy with blinatumomab and TKI, including CNS prophylaxis and bone marrow evaluations

3 cycles of 28 days each, with 14 days off between cycles

Maintenance Therapy

Patients achieving complete molecular response may proceed to maintenance therapy with additional cycles of blinatumomab and TKI

4 cycles of 28 days each, with 28 days off between cycles

Follow-up

Patients are monitored for long-term survival and relapse outcomes

2 years

Treatment Details

Interventions

• Blinatumomab
• Dasatinib

Trial Overview The trial is testing blinatumomab combined with tyrosine kinase inhibitor therapy (like dasatinib) against standard care for Ph+ ALL. The goal is to see if adding blinatumomab improves outcomes compared to just corticosteroids plus TKI therapy.

Participant Groups

Group I: Blinatumomab & Concurrent Oral Tyrosine Kinase Inhibitor (TKI) Experimental Treatment 4 Interventions

Patients may receive steroids and hydroxyurea pre-study entry and receive a 7-day steroid prephase before starting TKI therapy. Planned initial TKI is dasatinib 140 mg daily; dasatinib dose may be reduced or TKI may be changed to a different agent under certain conditions. Induction consists of continuous TKI + 24 days of dexamethasone, followed by taper of dexamethasone, with bone marrow aspirate/biopsy (BMA) and CNS prophylaxis at days 22 and 43. Patients achieving morphologic complete response post-induction proceed to consolidation with up to 3 cycles of blinatumomab (28-day cycles, 14 days between cycles) + TKI, with BMA and CNS prophylaxis between cycles. Patients achieving complete molecular response may proceed to maintenance with up to 4 more cycles of blinatumomab (28-day cycles with 28 days between cycles) + TKI, with CNS prophylaxis between cycles and BMA after cycles 5 and 7. Patients can come off study to undergo allogeneic hematopoietic cell transplantation at any time.

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

Approved in European Union as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• High-risk first relapse BCP-ALL

Approved in United States as Blincyto for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL)
• First or second complete remission with minimal residual disease (MRD)

Who Is Running the Clinical Trial?

Memorial Sloan Kettering Cancer Center

Lead Sponsor

Trials

1,998

Recruited

602,000+

Amgen

Industry Sponsor

Trials

1,508

Recruited

1,433,000+

Founded

1980

Headquarters

Thousand Oaks, USA

Known For

Human Therapeutics

Top Products

Enbrel, Prolia, Neulasta, Otezla

Robert A. Bradway

Amgen

Chief Executive Officer since 2012

MBA from Harvard Business School

Paul Burton

Amgen

Chief Medical Officer since 2023

MD from University of London, PhD in Molecular and Cellular Biology from Imperial College London

Findings from Research

Blinatumomab is a groundbreaking treatment for B-cell precursor relapsed/refractory acute lymphoblastic leukemia (ALL), showing the ability to induce deep remissions in some patients, but many still do not respond or relapse, highlighting the need for improved treatment strategies.

Understanding how patients respond or resist blinatumomab could help identify those who will benefit most, and combining it with other therapies or using it earlier in treatment protocols may enhance its effectiveness and reduce relapse rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific antibodies in acute lymphoblastic leukemia therapy. Chitadze, G., Laqua, A., Lettau, M., et al.[2021]

Blinatumomab pharmacokinetics were effectively modeled using a one-compartment linear model, showing a clearance rate of 2.22 L/h and a central volume of 5.98 L, based on data from 674 patients.

Body surface area (BSA) significantly affects the clearance of blinatumomab, particularly in pediatric patients, suggesting that BSA-based dosing is important for lighter patients to ensure effective treatment while minimizing variability.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Blinatumomab in Pediatric and Adult Patients with Hematological Malignancies. Clements, JD., Zhu, M., Kuchimanchi, M., et al.[2021]

In a study of 36 adults with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), blinatumomab treatment led to a high remission rate of 69%, with transient increases in liver enzymes and inflammatory markers that returned to baseline without clinical symptoms.

Patients who responded to blinatumomab exhibited significant T-cell expansion and specific immune responses, indicating that the drug effectively activates the immune system against leukemia cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL. Nägele, V., Kratzer, A., Zugmaier, G., et al.[2022]

Blinatumomab represents a significant advancement in immunotherapy for relapsed or refractory acute lymphoblastic leukemia (ALL), demonstrating unprecedented efficacy by stimulating a strong T-cell response, which is a departure from traditional chemotherapy.

While blinatumomab offers promising benefits, it also presents unique immunological toxicities and complex administration requirements, necessitating careful consideration of its use compared to other emerging therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab: enlisting serial killer T-cells in the war against hematologic malignancies. Rogala, B., Freyer, CW., Ontiveros, EP., et al.[2023]

Blinatumomab is a first-in-class bispecific T-cell engager that effectively targets both CD19 on B-cells and CD3 on T-cells, showing a high response rate of 43% for complete remission in patients with relapsed or refractory precursor B-cell acute lymphoblastic leukemia (B-ALL).

Patients treated with blinatumomab had a median overall survival of 6.1 months and 60% achieved minimal residual disease negativity, although common side effects included fever, neurological events, and anemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab: A First-in-Class Bispecific T-Cell Engager for Precursor B-Cell Acute Lymphoblastic Leukemia. Buie, LW., Pecoraro, JJ., Horvat, TZ., et al.[2018]

Blinatumomab (Blincyto) received accelerated approval for treating B-cell precursor acute lymphoblastic leukemia (ALL) in patients with minimal residual disease, highlighting its efficacy in maintaining remission in both adults and children.

As a bispecific CD19-directed CD3 T-cell engager, blinatumomab works by activating T-cells to target and eliminate leukemia cells, demonstrating a novel mechanism of action in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A closer look at blinatumomab. Mattison, RJ.[2018]

Blinatumomab (Blincyto) achieved a complete remission in 33% of patients with relapsed or refractory Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (ALL), indicating its efficacy as a treatment option.

However, the treatment is associated with frequent grade 3 or 4 adverse effects, highlighting the need for careful monitoring of patients during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab (Blincyto) for acute lymphoblastic leukemia. [2015]

References

1. England pubmed.ncbi.nlm.nih.gov

Bispecific antibodies in acute lymphoblastic leukemia therapy. [2021]

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

Molecular remission after combination therapy with blinatumomab and ponatinib with relapsed/refractory Philadelphia chromosome-positive acute lymphocytic leukemia: two case reports. [2021]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Population Pharmacokinetics of Blinatumomab in Pediatric and Adult Patients with Hematological Malignancies. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL. [2022]

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

Blinatumomab: enlisting serial killer T-cells in the war against hematologic malignancies. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Blinatumomab: A First-in-Class Bispecific T-Cell Engager for Precursor B-Cell Acute Lymphoblastic Leukemia. [2018]

7. United States pubmed.ncbi.nlm.nih.gov

A closer look at blinatumomab. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Blinatumomab (Blincyto) for acute lymphoblastic leukemia. [2015]