Blinatumomab for Acute Lymphoblastic Leukemia

Recruiting at 194 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

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

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

Compensation: Varies

Number of Visits: Unknown

669 Participants Needed

Trial Summary

What is the purpose of this trial?

This randomized phase III trial studies how well blinatumomab works compared with standard combination chemotherapy in treating patients with B-cell acute lymphoblastic leukemia that has returned after a period of improvement (relapsed). Immunotherapy with blinatumomab may allow the body's immune system to attack and destroy some types of leukemia cells. It is not yet known whether blinatumomab is more effective than standard combination chemotherapy in treating relapsed B-cell acute lymphoblastic leukemia.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there are specific requirements about the timing of previous treatments, such as a 14-day gap after cytotoxic therapy and a 7-day gap after biologic agents, except for certain allowed medications like hydroxyurea and intrathecal chemotherapy.

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

Blinatumomab has shown effectiveness in treating both adults and children with a type of blood cancer called B-cell acute lymphoblastic leukemia (ALL), especially in cases where the disease has returned or is resistant to other treatments. It works by helping the body's immune system attack cancer cells, leading to significant improvements in some patients. ^{1 2 3 4 5}

Is Blinatumomab safe for treating acute lymphoblastic leukemia?

Blinatumomab has been associated with serious side effects like cytokine release syndrome (a severe immune reaction) and neurological issues (such as seizures and confusion). However, most patients tolerate the treatment relatively well. ^{6 7 8 9 10}

What makes the drug Blinatumomab unique for treating acute lymphoblastic leukemia?

Blinatumomab is unique because it is a bispecific T cell-engaging antibody that targets CD19 on B-cells and CD3 on T-cells, helping the immune system attack leukemia cells. It is used for patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia, including those with minimal residual disease, and has shown effectiveness in inducing remission. ^{1 8 11 12 13}

Research Team

Patrick A Brown

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for young patients under 31 years old with a first relapse of B-cell acute lymphoblastic leukemia. They must not have had prior stem cell transplants or blinatumomab treatment, and their major organs need to function well. Patients with HIV, pregnant or breastfeeding women, and those with certain genetic syndromes or significant CNS pathology are excluded.

Inclusion Criteria

Specific criteria for direct bilirubin levels

I completed my last cancer treatment a specific time ago.

Requirement for written informed consent

Exclusion Criteria

I have Burkitt leukemia/lymphoma or mature B-cell leukemia.

I have B-lymphoblastic lymphoma.

Lactating females who plan to breastfeed

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Block 1

Patients receive a combination of chemotherapy drugs including dexamethasone, vincristine sulfate, pegaspargase, mitoxantrone hydrochloride, and methotrexate

4 weeks

Multiple visits for drug administration

Randomization and Treatment

Patients are randomized to receive either intensive chemotherapy blocks or blinatumomab blocks, followed by allogeneic HSCT if eligible

10-12 weeks

Regular visits for drug administration and monitoring

Continuation and Maintenance

Patients receive continuation therapy and maintenance, including chemotherapy and blinatumomab cycles

Up to 2 years

Regular visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 10 years

Treatment Details

Interventions

• Blinatumomab

Trial Overview The trial is testing the effectiveness of blinatumomab (an immunotherapy) against standard combination chemotherapy in treating relapsed B-cell acute lymphoblastic leukemia. It aims to see if blinatumomab can better engage the immune system to attack leukemia cells compared to traditional treatments.

Participant Groups

Group I: Arm D (LR blinatumomab) Experimental Treatment 15 Interventions

Patients receive Block 2 over 4 weeks, Blinatumomab Cycle 1 over 5 weeks, Continuation 1 over 8 weeks, Blinatumomab Cycle 2 over 5 weeks, Continuation 2 over 8 weeks, Blinatumomab Cycle 3 over 5 weeks, and then Maintenance.

Group II: Arm B (HR and IR blinatumomab) Experimental Treatment 7 Interventions

Patients receive Blinatumomab Block 1 over 5 weeks, Blinatumomab Block 2 over 5 weeks, and then undergo allogeneic HSCT.

Group III: Arm C (LR control) Active Control 15 Interventions

Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, Continuation 1 over 8 weeks, Continuation 2 over 8 weeks, and then Maintenance.

Group IV: Arm A (HR and IR control) Active Control 15 Interventions

Patients receive Block 2 over 4 weeks, Block 3 over 4 weeks, and then undergo allogeneic HSCT. Closed effective September 18, 2019.

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, 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]

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 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 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]

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 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]

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]

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]

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 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 (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]

In a phase 2 study, blinatumomab demonstrated a significant overall survival benefit for patients with relapsed/refractory Ph(-) B-precursor acute lymphoblastic leukemia, with a mean survival of 76.1 months compared to 39.8 months for historical patients receiving standard chemotherapy.

At 60 months, 12.6% of patients treated with blinatumomab were still alive, which is more than double the 5.4% survival rate of historical controls, indicating its potential as a more effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data. Barlev, A., Lin, VW., Katz, A., et al.[2021]

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]

References

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

A Systematic Review of Blinatumomab in the Treatment of Acute Lymphoblastic Leukemia: Engaging an Old Problem With New Solutions. [2021]

2. Korea (South) pubmed.ncbi.nlm.nih.gov

Immunoglobulin repletion during blinatumomab therapy does not reduce the rate of secondary hypogammaglobulinemia and associated infectious risk. [2022]

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

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

4. England pubmed.ncbi.nlm.nih.gov

Bispecific antibodies in acute lymphoblastic leukemia therapy. [2021]

5. China pubmed.ncbi.nlm.nih.gov

[Safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia]. [2023]

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

Blinatumomab: A First-in-Class Bispecific T-Cell Engager for Precursor B-Cell Acute Lymphoblastic Leukemia. [2018]

7. Switzerland pubmed.ncbi.nlm.nih.gov

The safety of blinatumomab in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis. [2022]

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

Blinatumomab (Blincyto) for acute lymphoblastic leukemia. [2015]

9. United States 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. [2023]

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

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

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

A closer look at blinatumomab. [2018]

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

Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data. [2021]

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

A Multidisciplinary Approach to Standardizing Processes for Blinatumomab Administration. [2017]