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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding blinatumomab (Blincyto) to the usual treatment with corticosteroids and a TKI, such as dasatinib (Sprycel), can more effectively treat individuals with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Researchers aim to improve patient responses compared to the standard treatment alone. The trial targets those with confirmed Ph+ ALL who have not received treatment beyond basic options like corticosteroids. Individuals with this type of leukemia who have not yet undergone extensive treatment might be suitable for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that patients generally tolerate the combination of blinatumomab and dasatinib well. Studies have reported encouraging survival rates; one study showed a 95% survival rate after 18 months, while another reported 80.7% survival after 53 months. Although some side effects may occur, many patients can manage them.

Real-world data from a study in China also support the safety of blinatumomab in newly diagnosed patients. While specific side effects were not listed, the ongoing use and study of this treatment combination suggest a reasonable safety profile.

Since this trial is in Phase 2, researchers are still evaluating the treatment's safety. However, early evidence suggests it might be safe for testing in a larger group. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of Blinatumomab and Dasatinib for treating Acute Lymphoblastic Leukemia (ALL) because this approach targets cancer in a novel way. Blinatumomab is a bispecific T-cell engager that helps the immune system recognize and attack leukemia cells, while Dasatinib is a tyrosine kinase inhibitor that blocks signals that promote cancer cell growth. Together, they offer a potent one-two punch that could lead to more effective and faster clearing of cancer cells compared to traditional chemotherapy. This combination also allows for a more tailored treatment approach, potentially improving outcomes for patients with ALL.

What evidence suggests that blinatumomab combined with TKI therapy could be an effective treatment for acute lymphoblastic leukemia?

In this trial, participants will receive a combination of blinatumomab and a tyrosine kinase inhibitor (TKI), with dasatinib as the planned initial TKI. Studies have shown that using blinatumomab and dasatinib together holds promise for treating Ph+ Acute Lymphoblastic Leukemia (ALL). One study found a 95% survival rate after 18 months with this combination. Another study reported that 75.8% of patients remained disease-free after 53 months. This treatment enhances the body's immune response against cancer cells. These findings suggest that adding blinatumomab to dasatinib could improve outcomes for people with Ph+ ALL. ^{1 2 6 7 8}

Who Is on the Research Team?

Mark Geyer, MD

Principal Investigator

Memorial Sloan Kettering Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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 (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 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 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]

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 (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]

Citations

1. nejm.org nejm.org/doi/full/10.1056/NEJMoa2016272

Dasatinib–Blinatumomab for Ph-Positive Acute ... At a median follow-up of 18 months, overall survival was 95% and disease-free survival was 88%; disease-free survival was lower among patients ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38127722/

Long-Term Results of the Dasatinib-Blinatumomab ... We report the long-term results of the frontline trial with dasatinib and blinatumomab in induction/consolidation (GIMEMA LAL2116, D-ALBA) for ...

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/838/530283/Immunomodulatory-Effect-of-Dasatinib-Plus

Immunomodulatory Effect of Dasatinib Plus Blinatumomab ... Our study shows that in adult Ph+ ALL front-line treatment with dasatinib and blinatumomab induces a more profound NK, T-NK and Treg immune ...

4. ascopubs.org ascopubs.org/doi/10.1200/JCO.23.01075

Long-Term Results of the Dasatinib-Blinatumomab ... The final analysis of the D-ALBA study shows that at a median follow-up of 53 months DFS and OS are 75.8% and 80.7%, respectively, which is ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124035857

Immunomodulatory Effect of Dasatinib Plus Blinatumomab ... Our study shows that in adult Ph+ ALL front-line treatment with dasatinib and blinatumomab induces a more profound NK, T-NK and Treg immune modulation.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11164718/

Real-world evidence on treatment pattern, effectiveness, and ... This retrospective study provided real-world data on the treatment pattern, effectiveness, and safety of blinatumomab in Chinese patients with newly diagnosed ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06124157

NCT06124157 | A Study Testing the Combination of ... Blinatumomab may strengthen the immune system's ability to fight cancer cells by activating the body's own immune cells to destroy the tumor. Dasatinib and ...

8. ashpublications.org ashpublications.org/bloodadvances/article/9/15/3946/537699/Blinatumomab-use-in-pediatric-B-ALL-where-are-we

Blinatumomab use in pediatric B-ALL: where are we now? Among 70 patients who received the recommended dosage, 27 (39%) achieved a complete remission (CR; defined as no circulating blasts or ...