Intrathecal Chemoprophylaxis for Acute Lymphoblastic Leukemia

Overseen By Caitlin Guzowski

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Northside Hospital, Inc.

Disqualifiers: CNS disorders, Prior blinatumomab, 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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new schedule for administering intrathecal chemotherapy, a cancer treatment delivered directly into the spinal fluid, to individuals with B-cell Acute Lymphoblastic Leukemia (ALL). The researchers aim to combine it with the drug blinatumomab (Blincyto) to effectively combat leukemia while minimizing side effects on the brain. Adults with a stubborn form of ALL who are beginning their first round of blinatumomab may find this trial suitable. Participants must have healthy liver and kidney function and should not have any active infections or other major health issues. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether 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 has shown that blinatumomab, a treatment for B-cell acute lymphoblastic leukemia (B-ALL), is generally well-tolerated. In studies, many patients who received the recommended dose went into remission, demonstrating its effectiveness. Although some patients experienced side effects, these were usually manageable.

The treatment has already received approval for other uses, indicating a certain level of safety. However, like any medication, it can cause side effects, including nerve damage. This trial aims to adjust the timing of chemotherapy to reduce this risk while maintaining the benefits of blinatumomab.

The trial seeks to find the safest way to use blinatumomab. It is important to consult a healthcare provider about potential risks before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for acute lymphoblastic leukemia, which typically involve systemic chemotherapy, blinatumomab offers a targeted approach. This drug is a type of immunotherapy known as a bispecific T-cell engager (BiTE), which uniquely directs the body's immune cells to attack cancer cells. Researchers are particularly excited about blinatumomab because it harnesses the immune system to fight leukemia more precisely, potentially leading to fewer side effects and improved outcomes. Additionally, by delivering it intrathecally, directly into the cerebrospinal fluid, blinatumomab may more effectively target leukemia cells that have spread to the central nervous system, a common complication in this type of cancer.

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

Research has shown that blinatumomab, which participants in this trial may receive, effectively treats B-cell acute lymphoblastic leukemia (B-cell ALL). In earlier studies, patients using blinatumomab showed significant improvements, with 78% showing no signs of remaining cancer cells after just one treatment cycle. Another study found that all new patients experienced complete or nearly complete remission, even if their blood counts weren't fully normal. Additionally, 87.2% of patients had no detectable cancer cells after two cycles. These results suggest that blinatumomab can effectively target leukemia cells and improve patient outcomes. ^{1 4 6 7 8}

Who Is on the Research Team?

Melhem Solh, MD

Principal Investigator

Blood and Marrow Transplant Group of Georgia

Are You a Good Fit for This Trial?

Adults with B-cell Acute Lymphoblastic Leukemia who are about to start their first cycle of blinatumomab can join. They must have good kidney and liver function, be HIV negative, not pregnant if applicable, and without active infections or other serious health issues that could interfere with the study.

Inclusion Criteria

I am starting blinatumomab for my relapsed or MRD-positive B-cell ALL.

Negative serum pregnancy test, if applicable

My kidney and liver are working well.

Exclusion Criteria

I do not have any infections or conditions that could affect the study.

My acute lymphoblastic leukemia has spread to my brain or spinal cord.

I cannot receive methotrexate injections into my spine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Intrathecal Chemotherapy

Participants receive intrathecal chemotherapy before and during blinatumomab to prevent neurotoxicity

4 weeks

Blinatumomab Therapy

Participants receive blinatumomab therapy with monitoring for neurotoxicity and cytokine release syndrome

4 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• Methotrexate

Trial Overview The trial is testing a new schedule for giving intrathecal chemotherapy (directly into the spinal fluid) alongside blinatumomab to see if it reduces brain-related side effects while still fighting leukemia effectively.

How Is the Trial Designed?

Group I: Intrathecal chemotherapy before blinatumomab Experimental Treatment 2 Interventions

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?

Northside Hospital, Inc.

Lead Sponsor

Trials

26

Recruited

1,100+

Published Research Related to This Trial

In a study of 33 children with refractory or relapsed precursor B-cell acute lymphoblastic leukemia (R/R-BCP-ALL), a short course of blinatumomab resulted in a high complete remission rate of 78.8%, with remission lasting approximately 14 days.

The treatment was associated with manageable side effects, including cytokine release syndrome in 54.5% of patients, but no treatment-related deaths, indicating that blinatumomab is both effective and safe for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-course blinatumomab for refractory/relapse precursor B acute lymphoblastic leukemia in children. Xie, J., Liu, S., Zhou, M., et al.[2023]

Blinatumomab monotherapy demonstrated a complete remission (CR) rate of 54% and a minimal residual disease (MRD) response rate of 43% in treating relapsed/refractory acute lymphoblastic leukemia (R/R B-ALL) across 18 studies involving 1,373 patients.

The treatment showed a manageable safety profile, with 80% of patients experiencing grade ≥3 adverse events, but only 7% experiencing significant neurological toxicity and 3% experiencing cytokine release syndrome, indicating that while effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Blinatumomab for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: A Systemic Review and Meta-Analysis. Liu, H., Xi, R., Mao, D., et al.[2023]

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 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]

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]

In a study of 23 adults with B-cell acute lymphoblastic leukemia treated with blinatumomab, pre-emptive intravenous immune globulin (IVIG) did not reduce the incidence of hypogammaglobulinemia or associated infections compared to a control group.

Both groups experienced similar rates of infections and immunoglobulin levels, indicating that IVIG repletion may not be effective in mitigating the risks associated with blinatumomab treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunoglobulin repletion during blinatumomab therapy does not reduce the rate of secondary hypogammaglobulinemia and associated infectious risk. Wo, S., Levavi, H., Mascarenhas, J., et al.[2022]

Blinatumomab, a bispecific T-cell-engaging antibody, has shown a response rate of 34% to 66% in heavily pretreated children with relapsed/refractory acute lymphoblastic leukemia (R/R-ALL), making it a promising treatment option, especially as a bridge to stem cell transplantation.

Recent randomized controlled trials indicate that blinatumomab leads to a greater reduction in minimal residual disease and improved survival compared to standard treatments, suggesting its potential for frontline use in high-risk patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab in Pediatric Acute Lymphoblastic Leukemia-From Salvage to First Line Therapy (A Systematic Review). Queudeville, M., Ebinger, M.[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]

Blinatumomab (Blincyto®) is an effective treatment for relapsed or refractory acute lymphoblastic leukemia, having received accelerated approval for its use.

A multidisciplinary collaboration among nursing, pharmacy, prescribers, and support staff is essential for the safe administration of blinatumomab, and this approach can be adapted by other institutions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multidisciplinary Approach to Standardizing Processes for Blinatumomab Administration. DePadova, S., Howlett, C., Rivera, K.[2017]

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 39 pediatric patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL), treatment with blinatumomab resulted in a complete remission (CR) rate of 46% for those with ≥5% blasts and 81% for those with <5% blasts, demonstrating its efficacy in inducing remission and reducing minimal residual disease (MRD).

The treatment was generally well tolerated, with 56.4% of patients experiencing adverse events, most of which were mild (≤2 grade), and only two patients required temporary discontinuation due to neurological side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab in Children and Adolescents with Relapsed/Refractory B Cell Precursor Acute Lymphoblastic Leukemia: A Real-Life Multicenter Retrospective Study in Seven AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) Centers. Beneduce, G., De Matteo, A., Stellato, P., et al.[2022]

Blinatumomab, a bispecific T-cell engager, significantly improves overall survival in adults and children with relapsed and refractory B-cell acute lymphoblastic leukemia (ALL), showing a median overall survival of 7.7 months compared to 4.0 months with standard chemotherapy.

The drug achieved a complete measurable residual disease response in 78% of patients in the phase II BLAST trial, but it is associated with potential side effects, including cytokine release syndrome and neurotoxicity in about 15% and 65% of patients, respectively.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of Blinatumomab in the Treatment of Acute Lymphoblastic Leukemia: Engaging an Old Problem With New Solutions. Halford, Z., Coalter, C., Gresham, V., et al.[2021]

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. aob.amegroups.org aob.amegroups.org/article/view/11031/html

Immunotherapy with blinatumomab in B-cell acute ... Overall, 78% of patients achieved MRD negativity after one cycle of blinatumomab (18). TOWER (NCT02013167), a phase III study, further explored ...

3. 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- ...

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 ... Blinatumomab is efficacious in patients with B-cell acute lymphoblastic leukemia (B-ALL), yet limited real-world data exists in this context.

7. blincytohcp.com blincytohcp.com/clinical-data/adult-aya/real-world-evidence-study

Real-World Evidence in Adult & AYA B-cell ALL See real-world clinical outcomes for BLINCYTO® (blinatumomab) in treating adult and AYA patients with B-cell acute lymphoblastic leukemia (ALL).

8. 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 Phase 3 Study Results Demonstrated Three Year, Disease-Free Survival of 96%. THOUSAND OAKS, Calif. , Dec. 7, 2024 /PRNewswire/ -- Amgen ...