Blinatumomab + Chemotherapy/Dasatinib for Acute Lymphoblastic Leukemia

Recruiting at 227 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

53 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Blinatumomab for treating Acute Lymphoblastic Leukemia?

Blinatumomab has shown effectiveness in treating relapsed or refractory acute lymphoblastic leukemia (ALL), with clinical trials demonstrating higher complete remission rates and improved survival compared to standard chemotherapy. In the TOWER trial, patients receiving Blinatumomab had a 34% complete remission rate compared to 16% with standard chemotherapy, and a median survival of 7.7 months versus 4.0 months. ^{1 2 3 4 5}

Is the combination of Blinatumomab and chemotherapy safe for treating acute lymphoblastic leukemia?

Blinatumomab, used in treating acute lymphoblastic leukemia, has shown some side effects like cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage), but these can be managed with strategies like premedication and dose adjustments. In trials, it was generally well-tolerated, and patients recovered from severe chemotherapy-related toxicity when treated with Blinatumomab. ^{1 2 5 6 7}

What makes the drug combination of Blinatumomab and Dasatinib unique for treating acute lymphoblastic leukemia?

This drug combination is unique because it offers a chemotherapy-free option for treating Philadelphia chromosome-positive acute lymphoblastic leukemia, with Blinatumomab engaging the immune system to target cancer cells and Dasatinib inhibiting cancer cell growth. This approach can lead to significant molecular responses with potentially fewer toxicities compared to traditional chemotherapy. ^{1 2 4 8 9}

What is the purpose of this trial?

This phase II trial studies the side effects and how well blinatumomab and combination chemotherapy or dasatinib, prednisone, and blinatumomab work in treating older patients with acute lymphoblastic leukemia. Immunotherapy with monoclonal antibodies, such as blinatumomab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as prednisone, vincristine sulfate, methotrexate, and mercaptopurine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Dasatinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving blinatumomab with combination chemotherapy or dasatinib and prednisone may kill more cancer cells.

Research Team

Anjali S Advani

Principal Investigator

SWOG Cancer Research Network

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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, 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]

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 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 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]

References

1. England pubmed.ncbi.nlm.nih.gov

Blinatumomab: enlisting serial killer T-cells in the war against hematologic malignancies. [2023]

2. England pubmed.ncbi.nlm.nih.gov

FDA Supplemental Approval: Blinatumomab for Treatment of Relapsed and Refractory Precursor B-Cell Acute Lymphoblastic Leukemia. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Bispecific antibodies in acute lymphoblastic leukemia therapy. [2021]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Blinatumomab in Pediatric Acute Lymphoblastic Leukemia-From Salvage to First Line Therapy (A Systematic Review). [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Blinatumomab: Bridging the Gap in Adult Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia. [2018]

6. New Zealand pubmed.ncbi.nlm.nih.gov

Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults. [2022]

7. United States 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. [2020]

8. United States pubmed.ncbi.nlm.nih.gov

Drug Combo May Obviate Chemotherapy in ALL. [2021]

9. United States 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. [2021]