Blinatumomab for Acute Lymphoblastic Leukemia and Non-Hodgkin's Lymphoma

Recruiting at 1 trial location

Overseen By Jonathan A. Webster

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Duration: 6 weeks per cycle

44 Participants Needed

Trial Summary

What is the purpose of this trial?

The investigators primary objective is to determine the safety and toxicity of incorporating blinatumomab into the post-allogeneic hematopoietic stem cell transplant (HSCT) maintenance setting for patients with CD19+-B-cell malignancies (Acute Lymphoblastic Leukemia \[ALL\], Non-Hodgkin's Lymphoma \[NHL\]).

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, like calcineurin inhibitors or other systemic immunosuppressants, at least 4 weeks before starting the treatment. If you're on steroids for GVHD, you need to be off them for at least 4 weeks too. It's best to discuss your specific medications with the trial team.

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

Blinatumomab has shown effectiveness in treating acute lymphoblastic leukemia (ALL), with a remission rate of 69% in a study involving patients with relapsed or hard-to-treat ALL. It works by activating the body's immune system to attack cancer cells, offering a new option for patients who did not respond to traditional chemotherapy. ^{1 2 3 4 5}

Is blinatumomab safe for humans?

Blinatumomab has been associated with some serious side effects, including cytokine release syndrome (a severe immune reaction) and neurological issues like seizures. However, these side effects can often be managed with medication or by stopping the treatment temporarily. ^{6 7 8 9 10}

How is the drug blinatumomab different from other treatments for acute lymphoblastic leukemia and non-Hodgkin's lymphoma?

Blinatumomab is unique because it is a bispecific T-cell engager that targets both CD19 on B cells and CD3 on T cells, helping the immune system attack cancer cells. It is administered as a continuous infusion over four weeks, which is different from many other treatments that are given in shorter, more intermittent doses. ^{1 2 6 9 11}

Research Team

Jonathan A. Webster

Principal Investigator

Johns Hopkins University

Ivana Gojo, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

Adults over 18 with B-cell malignancies like ALL or NHL, post-allogeneic HSCT. They must be in remission but at high risk of relapse, within a specific time frame from transplant, and have recovered blood counts without disease progression. Fertility requires contraception use during the study. Exclusions include recent chemo/radiotherapy, uncontrolled illnesses, certain medications for GVHD, poor organ function, pregnancy/lactation, infections like HIV/HBV/HCV, severe GVHD history or active CNS/testes disease.

Inclusion Criteria

I have high-risk Pre-B ALL in my first complete remission or am in my second or later complete remission.

I was treated with blinatumomab and my leukemia cells still have CD19.

I can take care of myself and perform daily activities.

Exclusion Criteria

I haven't had chemotherapy or radiotherapy in the last 2 weeks.

I have had severe acute or active severe chronic graft-versus-host disease.

I weigh less than 45 kg.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Blinatumomab is administered as a continuous intravenous (IV) infusion over four weeks followed by a two-week treatment-free interval

6 weeks per cycle

Hospitalization recommended for at least the first three days of the first cycle and the first two days of the second cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

Treatment Details

Interventions

• Blinatumomab

Trial Overview The trial is testing blinatumomab's safety as a maintenance therapy after allogeneic HSCT in patients with CD19+ B-cell cancers (ALL and NHL). It aims to prevent cancer recurrence by using different doses of blinatumomab along with dexamethasone to manage potential side effects.

Participant Groups

Group I: Post-alloHSCT Maintenance Experimental Treatment 4 Interventions

Blinatumomab will be administered as a continuous intravenous (IV) infusion over four weeks followed by a two-week treatment free interval. It is recommended that patients are hospitalized at least during the first three days of the first cycle and the first two days of the second cycles.

Who Is Running the Clinical Trial?

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Lead Sponsor

Trials

578

Recruited

33,600+

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

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]

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]

In a study of 36 adults with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), blinatumomab treatment led to a high remission rate of 69%, with transient increases in liver enzymes and inflammatory markers that returned to baseline without clinical symptoms.

Patients who responded to blinatumomab exhibited significant T-cell expansion and specific immune responses, indicating that the drug effectively activates the immune system against leukemia cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL. Nägele, V., Kratzer, A., Zugmaier, G., et al.[2022]

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, a bispecific T-cell engager, shows significant efficacy in treating refractory or relapsed acute lymphoblastic leukemia (ALL), achieving complete response rates of 39% to 69% and a median overall survival of 7.7 months, compared to 4.0 months with traditional chemotherapy.

The treatment has a favorable safety profile, with manageable side effects such as cytokine-release syndrome and reversible neurological issues, making it a promising option for both adult and pediatric patients with R/R ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotargeting relapsed or refractory precursor B-cell acute lymphoblastic leukemia - role of blinatumomab. Queudeville, M., Handgretinger, R., Ebinger, M.[2020]

Blinatumomab is an effective treatment for relapsed or refractory B-acute lymphoblastic leukemia (ALL), particularly in patients with minimal residual disease, as it engages T-cells to target CD19 positive B cells.

While it shows promise, blinatumomab can cause significant adverse effects, including infections and neurotoxicity, requiring careful management by experienced medical centers during its continuous four-week infusion administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical applications and safety evaluation of the new CD19 specific T-cell engager antibody construct blinatumomab. Wilke, AC., Gökbuget, N.[2017]

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 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]

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. China pubmed.ncbi.nlm.nih.gov

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

5. England pubmed.ncbi.nlm.nih.gov

Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL. [2022]

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

Immunotargeting relapsed or refractory precursor B-cell acute lymphoblastic leukemia - role of blinatumomab. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Clinical applications and safety evaluation of the new CD19 specific T-cell engager antibody construct blinatumomab. [2017]

10. 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]

11. 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]