Blinatumomab + Chemotherapy/Dasatinib for Acute Lymphoblastic Leukemia

Not currently recruiting at 233 trial locations

Age: 65+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Steroids, Hydroxyurea

Must not be taking: Proton pump inhibitors

Disqualifiers: CNS pathology, Autoimmune 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: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of different treatment combinations for older patients with acute lymphoblastic leukemia (ALL), a type of blood cancer. It examines two main treatments: blinatumomab, an immunotherapy that aids the immune system in fighting cancer, and dasatinib, which inhibits cancer cell growth. Participants will receive these treatments alongside standard chemotherapy drugs to determine which combination is most effective in killing cancer cells and to monitor side effects. Eligible participants have been diagnosed with ALL and have not received certain prior treatments. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, certain medications like proton pump inhibitors and some chemotherapy drugs must be stopped before registration. It's best to discuss your current medications with the study team to understand any specific requirements.

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

Research has shown that blinatumomab is generally well-tolerated for treating acute lymphoblastic leukemia. In real-world use, serious side effects occurred in about 12.5% of patients, indicating that most people manage it well. This medication helps the body's immune system fight cancer cells.

Dasatinib, also part of this trial, works by blocking enzymes that promote cancer growth. The FDA has approved it for other conditions, indicating its safety for humans. While specific side effect data is not provided here, its approval suggests it is usually safe with careful monitoring.

Overall, these treatments have shown promise with a safety profile that most people can handle well, though monitoring for side effects remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for Acute Lymphoblastic Leukemia (ALL) because they combine innovative therapies with traditional chemotherapy methods to enhance effectiveness. Blinatumomab is an immunotherapy that uniquely targets specific proteins on cancer cells, potentially improving the immune system's ability to attack leukemia cells more precisely. Dasatinib, on the other hand, is a targeted therapy that blocks certain enzymes involved in cancer cell growth, offering a more focused approach compared to conventional chemotherapy. Together, these treatments aim to provide a more comprehensive attack on leukemia cells, potentially leading to better outcomes for patients.

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

Research has shown that blinatumomab effectively treats certain types of acute lymphoblastic leukemia (ALL). One study found that 78% of patients achieved MRD (minimal residual disease) negativity, meaning no detectable cancer cells remained after treatment. In this trial, participants in Cohort I will receive blinatumomab with POMP chemotherapy, while those in Cohort II will receive dasatinib, prednisone, and blinatumomab. Dasatinib blocks enzymes that help cancer cells grow, potentially preventing leukemia from spreading. Both treatments have shown promise in improving patient outcomes. This combination aims to boost the immune system to fight cancer and halt cancer cell growth, offering a comprehensive approach to tackling ALL. ^{5 6 7 8 9}

Who Is on the Research Team?

Anjali S Advani

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for older patients (65+) with acute lymphoblastic leukemia (ALL), including those with Philadelphia chromosome positive ALL or Ph-like DSMKF. It's suitable for newly diagnosed, relapsed, or refractory cases. Participants must have a certain percentage of lymphoblasts in blood/marrow and be able to provide consent for immunogenicity testing. Exclusions include CNS3 status, Burkitt's leukemia, prior significant treatments for ALL within specific time frames before registration, uncontrolled infections, and other serious health conditions.

Inclusion Criteria

Patients known to be positive for HIV must meet specific additional criteria

Patients must not have any known autoimmune disease

I do not have any ongoing serious infections.

Exclusion Criteria

I do not have Burkitt's lymphoma.

I do not have CNS3 condition.

I have never had a stem cell transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Induction

Patients receive blinatumomab or dasatinib and prednisone based on cohort assignment

4-12 weeks

Continuous monitoring (in-person)

Re-Induction

Patients not achieving CR or CRi receive additional blinatumomab treatment

6 weeks

Continuous monitoring (in-person)

Post-Remission

Patients receive blinatumomab and dasatinib treatment based on cohort assignment

18 weeks

Continuous monitoring (in-person)

Maintenance

Patients receive POMP or dasatinib and prednisone treatment based on cohort assignment

18 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Every 3 months for 2 years, every 6 months for 2 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• Dasatinib
• Mercaptopurine
• Methotrexate
• Prednisone
• Vincristine
• Vincristine Sulfate

Trial Overview The trial tests blinatumomab combined with chemotherapy drugs like prednisone and vincristine versus dasatinib plus prednisone and blinatumomab in treating older adults with ALL. Blinatumomab is an immunotherapy that may help the immune system attack cancer cells while dasatinib targets enzymes needed by cancer cells to grow.

How Is the Trial Designed?

Group I: Cohort II (dasatinib, prednisone, blinatumomab) Experimental Treatment 11 Interventions

See Detailed Description

Group II: Cohort I (blinatumomab, POMP) Experimental Treatment 15 Interventions

See Detailed Description

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?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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]

Blinatumomab is a promising new treatment for adults with relapsed or refractory B-cell acute lymphoblastic leukemia, showing effectiveness in targeting and destroying tumor cells by engaging both T-cells and B-cells.

While there are potential side effects like immunological toxicities and cytokine release syndrome, most patients tolerate blinatumomab well, indicating a favorable safety profile compared to traditional therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults. Lee, KJ., Chow, V., Weissman, A., 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 shown a 43% response rate in adult patients with relapsed or refractory Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia, with 40% of responders achieving complete remission and proceeding to stem cell transplantation.

Management strategies, such as premedication with dexamethasone and gradual dose escalation, have successfully reduced the incidence and severity of adverse effects like cytokine release syndrome and neurotoxicity associated with early use of blinatumomab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab: Bridging the Gap in Adult Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia. Folan, SA., Rexwinkle, A., Autry, J., et al.[2018]

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 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, 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 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]

Citations

1. 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.

2. nejm.org nejm.org/doi/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).

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. 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 ...

5. 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12325004/

Blinatumomab in pediatric B-acute lymphoblastic leukemia Extended follow-up data revealed that patients receiving blinatumomab consolidation therapy maintained event-free survival (EFS) exceeding 50% ...

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. 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 ...

9. nature.com nature.com/articles/s41408-024-01179-4

Frontline Ph-negative B-cell precursor acute lymphoblastic ... Additionally, 3-year relapse-free survival was 80% for the blinatumomab arm versus 64% for chemotherapy alone (HR, 0.53 [95% CI, 0.32–0.87]; P = ...