BLINCYTO for Leukemia

Overseen By Ashkan Emadi, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Maryland, Baltimore

Must be taking: Intrathecal chemotherapy

Must not be taking: Investigational agents

Disqualifiers: CNS pathology, Cytogenetic abnormalities, 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

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

Compensation: Varies

Number of Visits: Unknown

2 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a research study to find out if a drug called blinatumomab is effective for treating patients with relapsed or refractory (R/R) or measurable residual disease (MRD) CD19-positive mixed phenotypic acute leukemia (MPAL). Measurable Residual Disease (MRD) means that there are a small number of cancer cells remaining after treatment

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on other investigational drugs, chemotherapy, radiation, or immunotherapy (except corticosteroids or hydroxyurea). It's best to discuss your current medications with the study team.

Is Blincyto (Blinatumomab) safe for humans?

Blincyto (Blinatumomab) has been associated with serious side effects like cytokine release syndrome (a severe immune reaction) and neurologic events (problems with the nervous system), as well as common side effects like fever, headache, and nausea. It is important to discuss these risks with your healthcare provider. ^{1 2 3 4 5}

What makes the drug Blinatumomab (Blincyto) unique for treating leukemia?

Blinatumomab (Blincyto) is unique because it is a bispecific T-cell engaging antibody that connects T-cells to cancer cells, specifically targeting CD19 antigens on leukemia cells, which helps the immune system destroy them. This mechanism is different from traditional chemotherapy and is particularly used for patients with relapsed or hard-to-treat acute lymphoblastic leukemia. ^{1 2 6 7 8}

What data supports the effectiveness of the drug Blincyto for leukemia?

Research shows that Blincyto (Blinatumomab) can help about 33% of patients with a specific type of leukemia (acute lymphoblastic leukemia) achieve complete remission, meaning their cancer is no longer detectable. ^{1 2 6 7 9}

Who Is on the Research Team?

Vu H Duong, MD

Principal Investigator

University of Maryland, Baltimore

Are You a Good Fit for This Trial?

Adults with relapsed or refractory CD19-positive mixed phenotypic acute leukemia (MPAL) or those in remission but with detectable cancer cells after treatment. Participants must be over 18, have stable vital organ functions, and women of childbearing age must test negative for pregnancy. Those who've had a stem cell transplant should be past certain recovery milestones.

Inclusion Criteria

Direct bilirubin ≤ 2.5 mg/dL

I am of childbearing age and have a negative pregnancy test.

Ability to understand and willingness to sign a written informed consent document

Exclusion Criteria

My acute leukemia has specific genetic changes.

I have a very high white blood cell count but can take hydroxyurea for it.

I do not have any severe illnesses that my doctor thinks would interfere with the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Participants receive blinatumomab by continuous IV infusion for 28 days followed by a 14±3 days treatment-free interval

6 weeks

Consolidation

Participants continue to receive blinatumomab by continuous IV infusion for 28 days followed by a 28±3 days treatment-free interval

8 weeks

Maintenance

Participants receive blinatumomab by continuous IV infusion for 28 days followed by a 56±3 days treatment-free interval

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab

Trial Overview The trial is testing the effectiveness of blinatumomab for patients with specific types of acute leukemia that are either not responding to standard treatments or have lingering cancer cells post-treatment. The study focuses on how well this drug can treat these conditions.

How Is the Trial Designed?

Group I: Subjects with R/R CD19-positive MPAL Experimental Treatment 1 Intervention

Cohort A: Evaluate the efficacy of blinatumomab to achieve the best morphologic response after the first two cycles of therapy in subjects with morphologic R/R CD19-positive MPAL * The treatment of blinatumomab consists of induction, consolidation and maintenance therapy * Subject will receive study drug blinatumomab by continuous IV infusion (CIV) * Each treatment cycle consists of 28 days of blinatumomab CIV followed by a 14±3 days treatment-free interval for induction, 28±3 days treatment-free interval for consolidation, and 56±3 days treatment-free interval for maintenance * The initial dose of blinatumomab is 9 mcg/day for 7 days. The target dose for rest of treatment is 28 mcg/day

Group II: Subjects with CD19-positive MPAL in CR/CRh/CRi/CRp and detectable MRD Experimental Treatment 1 Intervention

Cohort B: Evaluate the efficacy of blinatumomab to achieve MRD-negativity in subjects with CD19-positive MPAL in CR, or CRh, or CRi or CRp after receiving at least one chemotherapy block of standard ALL or AML treatment with MRD-positivity at a level of ≥ 0.1% using an assay with a minimum sensitivity of 0.01% * The treatment of blinatumomab consists of induction, consolidation and maintenance therapy * Subject will receive study drug blinatumomab by continuous IV infusion (CIV) * Each treatment cycle consists of 28 days of blinatumomab CIV followed by a 14±3 days treatment-free interval for induction, 28±3 days treatment-free interval for consolidation, and 56±3 days treatment-free interval for maintenance. * The dose of blinatumomab is 28 mcg/day

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?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Published Research Related to This Trial

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 (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]

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 (BLINCYTO™) is a bispecific T-cell engaging antibody that effectively targets CD19 on B-cell cancers, activating T cells to induce cell lysis, making it a promising treatment for hematological cancers.

Approved by the US FDA in December 2014 for relapsed/refractory B-cell precursor acute lymphoblastic leukemia (BCP-ALL), blinatumomab is currently undergoing further development and awaiting EU approval.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab: first global approval. Sanford, M.[2020]

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 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) received accelerated FDA approval for treating relapsed or refractory precursor B-cell acute lymphoblastic leukemia (R/R ALL) based on a trial with 185 adults, showing a complete remission rate of 32% and a median response duration of 6.7 months.

While blinatumomab is effective, it is associated with serious side effects like cytokine release syndrome and neurological events, along with common adverse reactions such as fever, headache, and neutropenia, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval: Blinatumomab. Przepiorka, D., Ko, CW., Deisseroth, A., et al.[2021]

Blinatumomab is a first-in-class immunotherapy that effectively treats B-cell malignancies by engaging the patient's T cells to target CD19-expressing tumor cells, showing significant efficacy in relapsed B-cell Acute Lymphoblastic Leukemia (B-ALL) and B-cell Non-Hodgkin's Lymphoma.

Clinical trials have demonstrated its effectiveness even in patients who are resistant to chemotherapy, highlighting its potential as a vital treatment option in difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Blinatumomab, a bispecific B-cell and T-cell engaging antibody, in the treatment of B-cell malignancies. Burt, R., Warcel, D., Fielding, AK.[2020]

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]

Citations

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

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

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

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

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

Blinatumomab: A New Treatment for Adults With Relapsed Acute Lymphocytic Leukemia. [2017]

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

Blinatumomab: first global approval. [2020]

5. 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]

6. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

FDA Approval: Blinatumomab. [2021]

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

Blinatumomab, a bispecific B-cell and T-cell engaging antibody, in the treatment of B-cell malignancies. [2020]

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

A closer look at blinatumomab. [2018]