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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called blinatumomab (also known as BLINCYTO) for individuals with a type of leukemia that has returned or is difficult to treat. The goal is to determine if blinatumomab can reduce or eliminate remaining cancer cells after other treatments. Participants will receive the drug through an IV in cycles, with breaks in between. Suitable candidates have CD19-positive leukemia and have previously undergone some chemotherapy but still have cancer cells present. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

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 there any evidence suggesting that blinatumomab is likely to be safe for humans?

Research has shown that the FDA has already approved blinatumomab for treating certain types of leukemia, indicating thorough safety testing in those cases. Studies have found that patients usually tolerate blinatumomab well, though some risks exist. Common side effects include cytokine release syndrome, where the immune system overreacts, and neurological issues such as confusion or seizures. While these side effects are important to consider, many patients find that the benefits of the treatment often outweigh these risks. It is essential to consult a healthcare professional to determine if this treatment is appropriate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for leukemia?

Researchers are excited about blinatumomab for leukemia because it offers a unique approach compared to traditional chemotherapy. Blinatumomab is a type of immunotherapy known as a bispecific T-cell engager (BiTE), which works by directing the body's immune cells to attack cancer cells specifically. This targeted mechanism is different from conventional treatments, which often affect both healthy and cancerous cells. Moreover, blinatumomab is administered through continuous IV infusion, which allows for a steady and controlled delivery of the drug, potentially leading to better outcomes with fewer side effects. These features make blinatumomab a promising option for patients with CD19-positive leukemia.

What evidence suggests that blinatumomab might be an effective treatment for leukemia?

Research has shown that blinatumomab effectively treats certain types of leukemia, particularly those that are CD19-positive. In this trial, participants will receive blinatumomab to evaluate its efficacy in different contexts. For patients whose leukemia has returned or hasn't responded to other treatments, blinatumomab can help eliminate cancer cells and prepare them for a stem cell transplant. It is also being tested for patients with measurable residual disease (MRD), where a small number of cancer cells remain after treatment. Overall, blinatumomab has a strong track record in treating challenging leukemia cases. ^{1 3 5 6 7}

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 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) 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 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) 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 (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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11327717/

Effective treatment of relapsed/refractory CD19‐positive B ... Blinatumomab might be a promising treatment and a bridge to stem cell transplantation even in relapsed/refractory CD19‐expressing MPAL‐B/T.

2. sciencedirect.com sciencedirect.com/science/article/pii/S0145212625005880

Efficacy and safety of blinatumomab for CD19 + acute ... Blinatumomab has proven efficacy in the frontline, consolidation, and relapsed/refractory settings in B cell acute lymphoblastic leukemia. Its efficacy and ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07222579

Subcutaneous Blinatumomab for Treatment of Adult ... An arm type in which a group of participants receives an intervention/treatment considered to be effective (or active) by health care providers.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6439498/

Concomitant use of blinatumomab and donor lymphocyte ... Outcomes for MPAL are poor when compared with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) [2,6,7]. According to the WHO criteria, B-cell ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04827745?term=AREA%5BBasicSearch%5D(cd19)&rank=10

Blinatumomab for Treatment of R/R or MRD-positive CD19- ... 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 ...

6. blincytohcp.com blincytohcp.com/

BLINCYTO® (blinatumomab): CD19-Positive B-Cell Precursor ... IMPORTANT SAFETY INFORMATION. WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME.

7. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/966/499579/Blinatumomab-in-Combination-with-Immune-Checkpoint

Blinatumomab in Combination with Immune Checkpoint ... Based on this safety and efficacy data, blina + nivo was expanded to include 6 additional pts without additional DLTs. There were 2 DLTs at DLB1 ...