Blinatumomab and Chemotherapy for Acute Lymphoblastic Leukemia

Recruiting at 265 trial locations

Overseen By Amgen Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Amgen

Disqualifiers: CNS leukemia, Autoimmune disease, HIV, Hepatitis, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

304 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for acute lymphoblastic leukemia (ALL), a type of blood cancer, using the drug blinatumomab (also known as Blincyto) with low-intensity chemotherapy. The goal is to determine if this combination is safer and more effective than standard chemotherapy alone. Individuals newly diagnosed with Philadelphia-negative B-cell precursor ALL, who have health conditions making intense chemotherapy risky, might be suitable candidates. By comparing different treatment approaches, the trial aims to improve survival outcomes for participants. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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

Research shows that blinatumomab, combined with mild chemotherapy, is generally easy for patients to handle. In previous studies, patients who received this treatment combination had encouraging results, with many remaining disease-free. Specifically, one study found that 97.5% of patients with an average risk of relapse were disease-free after three years.

Additionally, real-world data from Chinese patients showed good results in treatment success and safety. Although some patients experienced side effects, these were manageable and did not outweigh the survival benefits.

Since this treatment is being tested in a late-stage trial, earlier tests have demonstrated its safety for broader use. This is a positive sign for those considering joining the trial, as it indicates the treatment has passed several safety checks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about blinatumomab for acute lymphoblastic leukemia because it offers a novel approach compared to standard chemotherapy regimens like GMALL or HyperCVAD. Blinatumomab is a bispecific T-cell engager, which means it works by connecting cancer cells to the body's T-cells, effectively directing the immune system to attack the leukemia cells. This treatment is unique because it can potentially target cancer cells more precisely than traditional chemotherapy, which often affects both healthy and cancerous cells. Additionally, the alternating regimen with low-intensity chemotherapy may reduce the intensity of side effects typically associated with standard chemotherapy.

What evidence suggests that this trial's treatments could be effective for acute lymphoblastic leukemia?

Research has shown that blinatumomab, when combined with mild chemotherapy, holds promise for treating acute lymphoblastic leukemia (ALL). In this trial, some participants will receive blinatumomab alternating with a low-intensity chemotherapy regimen. In children whose B-cell ALL returned, blinatumomab significantly improved health outcomes. Specifically, studies found that all newly diagnosed patients achieved complete remission, with no signs of cancer, or nearly complete remission after using blinatumomab. Most of these patients also had no detectable cancer cells after two treatment cycles. This suggests that blinatumomab, particularly when combined with chemotherapy, could effectively treat ALL. ^{1 5 6 7 8}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

Adults aged 55+ with newly diagnosed Philadelphia-negative B-cell precursor acute lymphoblastic leukemia (ALL) can join. Those 40-54 with severe comorbidities may also qualify. Participants need an ECOG performance status ≤2, adequate kidney and liver function, and a heart ejection fraction ≥50%. Exclusions include active CNS leukemia, autoimmune diseases affecting the CNS, HIV/Hepatitis B or C infections, uncontrolled chronic infections, or prior cancer chemotherapy for ALL.

Inclusion Criteria

I have been recently diagnosed with a specific type of leukemia that is not Philadelphia chromosome-positive.

I am 55 years old or older.

I can care for myself but may not be able to do heavy physical work, unless it's due to my leukemia.

Exclusion Criteria

My leukemia in the brain is not responding to spinal fluid chemotherapy.

I am HIV positive.

I have B cell ALL and may have had initial chemo but not started the main treatment yet.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Evaluate the safety and tolerability of blinatumomab alternating with low-intensity chemotherapy

Up to 14 weeks

Multiple visits for monitoring and dose adjustments

Phase 3 Treatment

Participants receive blinatumomab alternating with low-intensity chemotherapy or standard of care chemotherapy

Up to 5 years

Regular visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• Low-intensity chemotherapy regimen
• SOC chemotherapy regimen

Trial Overview The trial is testing blinatumomab alternating with low-intensity chemotherapy against standard of care (SOC) chemotherapy in older adults. It aims to see which treatment is safer and improves event-free survival (EFS) and overall survival (OS). The first part checks safety; the second compares how long patients live without events like disease worsening.

How Is the Trial Designed?

Group I: Safety Run-in: Blinatumomab alternating with low-intensity chemotherapy Experimental Treatment 2 Interventions

The safety run-in will be performed prior to initiating the phase 3 randomized part of the study. This safety run-in is to evaluate the safety and tolerability of blinatumomab alternating with low-intensity chemotherapy. The safety run-in also evaluates a shorter dose step interval from (4 days instead of 7 days) and a 1-week (instead of 2-week) drug free interval between blinatumomab cycles. Blinatumomab will be infused at a lower dose for 4 days and increase to a higher dose on Day 5 of the infusion for the remainder of the infusion.

Group II: Phase 3: Blinatumomab alternating with low-intensity chemotherapy Experimental Treatment 2 Interventions

Participants will receive blinatumomab alternating with low-intensity chemotherapy.

Group III: Phase 3: Standard of care (SOC) chemotherapy Active Control 1 Intervention

Participants will receive 1 of 2 SOC chemotherapy regimens (GMALL or HyperCVAD) per investigator's choice.

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?

Amgen

Lead 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, a bispecific T-cell engager, has been successfully used in 11 pediatric patients with relapsed/refractory acute lymphoblastic leukemia (ALL) after they experienced severe chemotherapy-induced toxicity, leading to recovery in all cases.

This treatment offers a nonmyelotoxic alternative for patients who cannot tolerate traditional cytotoxic therapies, suggesting it could be a valuable option in managing severe toxicity during leukemia treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab as a bridge to further therapy in cases of overwhelming toxicity in pediatric B-cell precursor acute lymphoblastic leukemia: Report from the Israeli Study Group of Childhood Leukemia. Elitzur, S., Arad-Cohen, N., Barzilai-Birenboim, S., et al.[2020]

In a study of 646 adult patients with relapsed/refractory acute lymphoblastic leukaemia, blinatumomab dosing at 28 μg/day was linked to a higher likelihood of achieving complete remission and a longer overall survival compared to standard chemotherapy.

The blinatumomab dosing regimen did not increase the risk of cytokine release syndrome or neurological events, indicating it is a safe treatment option for managing these potential side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exposure-response analysis of blinatumomab in patients with relapsed/refractory acute lymphoblastic leukaemia and comparison with standard of care chemotherapy. Kuchimanchi, M., Zhu, M., Clements, JD., et al.[2021]

Blinatumomab is an effective treatment for patients with relapsed or refractory Philadelphia chromosome-negative B-cell acute lymphocytic leukemia (ALL), as demonstrated in two phase II clinical trials.

Patients who achieve remission with blinatumomab may be eligible for stem cell transplantation, offering a potential cure for their leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab: A New Treatment for Adults With Relapsed Acute Lymphocytic Leukemia. Turner, J., Schneider, SM.[2017]

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) 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 has been approved for treating relapsed or refractory precursor B-cell acute lymphoblastic leukemia (ALL), showing a significant improvement in overall survival and complete remission rates compared to standard chemotherapy, with a median survival of 7.7 months versus 4.0 months for chemotherapy.

In clinical trials, blinatumomab demonstrated a complete remission rate of 34% in Philadelphia chromosome (Ph)-negative ALL and 31% in Ph-positive ALL, while also presenting some adverse events like cytokine release syndrome and neurological issues, although it had fewer cases of neutropenia and infections compared to standard treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Supplemental Approval: Blinatumomab for Treatment of Relapsed and Refractory Precursor B-Cell Acute Lymphoblastic Leukemia. Pulte, ED., Vallejo, J., Przepiorka, D., et al.[2019]

In a phase 3 clinical trial involving 669 patients aged 1 to 30 years with first relapse of B-cell acute lymphoblastic leukemia (B-ALL), substituting blinatumomab for intensive chemotherapy in consolidation therapy showed a 2-year disease-free survival rate of 54.4% compared to 39.0% for the chemotherapy group, suggesting a potential benefit of blinatumomab in this high-risk population.

Blinatumomab also demonstrated a better safety profile, with significantly lower rates of serious adverse events such as infections and febrile neutropenia compared to traditional chemotherapy, indicating it may be a safer option for treating relapsed B-ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. Brown, PA., Ji, L., Xu, X., et al.[2021]

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/NEJMoa2411680

Blinatumomab in Standard-Risk B-Cell Acute ... Treatment with blinatumomab has been shown to improve outcomes in children with relapsed B-cell acute lymphoblastic leukemia (B-cell ALL).

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38662275/

Real-world evidence on treatment pattern, effectiveness ... The ND patients using blinatumomab induction therapy achieved 100% CR/CRi rate; 87.2% achieved MRD negativity within two cycles of blinatumomab. In R/R re- ...

3. cancer.gov cancer.gov/news-events/cancer-currents-blog/2025/childhood-leukemia-blincyto-first-treatment

Blincyto Effective as Initial Treatment for Childhood ALL - NCI Children in the trial treated with the combination of blinatumomab and a standard chemotherapy regimen had a substantial improvement in disease-free survival.

4. 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6173178/

Impact of blinatumomab on patient outcomes in relapsed ... A majority of the events resolved, and there were no treatment-related deaths. Overall, these data showed that blinatumomab was effective in patients with MRD ...

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. amgen.com amgen.com/newsroom/press-releases/2024/12/blincyto-blinatumomab-added-to-chemotherapy-significantly-improves-survival-in-newly-diagnosed-pediatric-patients-with-bcell-precursor-acute-lymphoblastic-leukemia-ball

Press Releases BLINCYTO (BLINATUMOMAB) added to chemotherapy significantly improves survival in newly diagnosed pediatric patients with B-cell precursor acute lymphoblastic ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04994717

NCT04994717 | Study Comparing Blinatumomab ... The safety run-in part of the study aims to evaluate the safety and tolerability of blinatumomab alternating with low-intensity chemotherapy.