New Therapies for Acute Lymphoblastic Leukemia

Recruiting at 1 trial location

Overseen By Seth E. Karol, MD, MSCI

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: St. Jude Children's Research Hospital

Disqualifiers: CNS pathology, Autoimmune disease, Uncontrolled infection, 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

128 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two new treatments, inotuzumab and blinatumomab (also known as Blincyto), for children and young adults newly diagnosed with B-cell precursor acute lymphoblastic leukemia or lymphoma. The study aims to determine if these treatments lead to a better response than traditional methods. It also evaluates safety and impact on survival. The trial seeks participants diagnosed with these conditions who have received minimal treatment, particularly those with high-risk features like elevated white blood cell counts or specific disease spread, such as in the central nervous system or testicles. As a Phase 2 trial, the research focuses on measuring 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. However, it mentions that no prior chemotherapy is allowed, except for specific cases. It's best to discuss your current medications with the trial team to get a clear answer.

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

Previous studies have shown that blinatumomab is generally safe. Serious side effects occurred in 12.5% of patients, but many tolerated the treatment well without major issues. This suggests that blinatumomab is usually well-tolerated by patients with B-cell acute lymphoblastic leukemia.

Research on inotuzumab also indicates it is generally safe. Studies found it to be well-tolerated, even when combined with chemotherapy, suggesting that serious side effects are uncommon.

Both treatments have demonstrated promising safety results in earlier studies. However, patients should always consult their healthcare provider to understand what these findings mean for them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Blinatumomab and Inotuzumab for acute lymphoblastic leukemia (ALL) because these treatments offer a unique approach compared to traditional chemotherapy. Blinatumomab is a bispecific T-cell engager that directs the body's immune system to target and destroy cancer cells, offering a novel mechanism where it connects T-cells to cancer cells, leading to their destruction. Inotuzumab, on the other hand, is an antibody-drug conjugate that delivers a potent anti-cancer drug directly to the leukemia cells, minimizing damage to healthy cells. These treatments provide targeted action, which could potentially lead to more effective outcomes with fewer side effects than conventional therapies.

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

Research has shown that blinatumomab yields promising results for treating B-cell acute lymphoblastic leukemia (B-cell ALL) in children. Studies have found that, when combined with chemotherapy, it helps patients remain cancer-free longer. In one study, 39% of children achieved complete remission, with no signs of cancer detected.

Inotuzumab has also proven effective in treating B-cell ALL. In a study, 74% of patients achieved complete remission or remission with some recovery, and 82% reached minimal residual disease (MRD) negativity, indicating very few cancer cells remained. Both blinatumomab and inotuzumab are being tested together as part of the initial therapy in this trial to determine if they can improve remission rates in high-risk patients. ^{1 4 6 7 8}

Who Is on the Research Team?

Seth E. Karol, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for children and young adults newly diagnosed with B-cell precursor acute lymphoblastic leukemia or lymphoma. Participants should not have favorable genetic features and must be considered high-risk by the National Cancer Institute's criteria.

Inclusion Criteria

My liver and kidneys are working well.

My condition meets the criteria for lymphoblastic lymphoma.

Enrollment on INITIALL

Exclusion Criteria

I have an active autoimmune disease or a history of one that could affect my brain.

I have had a condition where small veins in my liver were blocked.

I am not willing to use birth control.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive induction therapy including dexamethasone, vincristine, inotuzumab, blinatumomab, dasatinib, and IT MHA

6 weeks

Weekly visits for treatment administration

Early Post Induction

Includes Consolidation, Blinatumomab 1, High-Dose Methotrexate, Reinduction, Interim, Reconsolidation, and Blinatumomab 2

Approximately 56 days

Maintenance

Maintenance therapy includes dexamethasone, vincristine, methotrexate, 6-mercaptopurine, thioguanine, dasatinib, and IT MHA

80 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Until remission for 10 years and at least 18 years old

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• Inotuzumab

Trial Overview The trial tests two immunotherapy drugs, inotuzumab and blinatumomab, during the first treatment phase (induction therapy). It aims to see if these drugs can lead to a higher rate of no detectable cancer cells compared to previous standard treatments.

How Is the Trial Designed?

Group I: SJALL23H Treated Patients Experimental Treatment 13 Interventions

All eligible patients receive intervention according to the Detailed Description section with the following: Induction: Dexamethasone, Vincristine, Inotuzumab, Blinatumomab, Cyclophosphamide, Dasatinib, IT MHA. Early Post Induction: Cyclophosphamide, Cytarabine, Inotuzumab, Methotrexate, IT MHA, Dasatinib, Blinatumomab, 6-mercaptopurine, Dexamethasone, Vincristine, Daunorubicin, Calaspargase. Maintenance: Dexamethasone, Vincristine, Methotrexate, 6-mercaptopurine, Thioguanine, Dasatinib, IT MHA.

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?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Pfizer

Industry Sponsor

Trials

4,712

Recruited

50,980,000+

Known For

Vaccine Innovations

Top Products

Viagra, Zoloft, Lipitor, Prevnar 13

Albert Bourla

Pfizer

Chief Executive Officer since 2019

PhD in Biotechnology of Reproduction, Aristotle University of Thessaloniki

Patrizia Cavazzoni

Pfizer

Chief Medical Officer

MD from McGill University

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 (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 shows a favorable safety profile in pediatric patients with B-cell acute lymphoblastic leukemia (ALL), associated with a lower risk of serious adverse events, febrile neutropenia, and infections compared to traditional chemotherapy.

While blinatumomab does not significantly increase the risk of cytokine release syndrome or seizures, it is linked to a higher risk of encephalopathy, indicating the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of blinatumomab in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis. Marrapodi, MM., Mascolo, A., di Mauro, G., et al.[2022]

In a study of six children with relapsed/refractory acute lymphoblastic leukemia (R/R-ALL), blinatumomab demonstrated good short-term safety and effectiveness, with three children achieving complete remission after treatment.

Five out of six children experienced cytokine release syndrome (CRS), indicating a manageable side effect profile, and the overall survival rate was 41.7% with a median survival time of 126 days, suggesting potential for further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia]. Li, XL., Liu, LP., Liu, F., et al.[2023]

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]

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 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 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]

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]

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. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9813344/

Real-world use of blinatumomab in adult patients with B-cell ... In a Phase 2 trial in patients with R/R Ph+ B-cell ALL, 36% of patients achieved complete remission (CR), of whom 88% attained MRD negativity [ ...

3. 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 ...

4. 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.

5. stjude.org stjude.org/research/progress/2024/blinatumomab-added-to-chemo-improves-survival-for-adults-with-all.html

Blinatumomab added to chemotherapy improves survival ... B-cell precursor acute lymphoblastic leukemia (B-ALL) has a cure rate exceeding 85% in children, but outcomes in adults are poor.

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

Real-world evidence on treatment pattern, effectiveness ... Grade ≥ 3 adverse events were observed in 12.5% patients. Blinatumomab was found to be effective with a tolerable safety profile in real world setting. Keywords ...

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 ...