Blinatumomab for Acute Lymphoblastic Leukemia

Recruiting at 70 trial locations

Overseen By Amgen Call Center

Age: Any Age

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Amgen

Disqualifiers: CNS leukemia, CNS pathology, others

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

281 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new method of administering the drug blinatumomab (Blincyto) to individuals with Acute Lymphoblastic Leukemia (ALL) that has returned or is unresponsive to other treatments. The trial aims to assess the safety and effectiveness of the drug when given under the skin and to determine the optimal dose. It targets patients whose leukemia worsens despite treatments like chemotherapy or stem cell transplants. Suitable candidates have experienced a relapse of B-precursor ALL after initial treatments and have more than 5% cancer cells in their bone marrow. As a Phase 1, Phase 2 trial, this research seeks to understand the treatment's mechanism and measure its effectiveness in an initial, smaller group, offering participants a chance to contribute to significant medical advancements.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking your current medications. However, you cannot have had cancer chemotherapy within 2 weeks or immunotherapy within 4 weeks before starting the trial. It's best to discuss your current medications with the trial team.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does mention that cancer chemotherapy and immunotherapy should not be taken within 2 to 4 weeks before starting the trial. It's best to discuss your current medications with the trial team to get specific guidance.

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

Research has shown that under-the-skin blinatumomab has been tested in several studies for safety. One study found it safe for patients who had already received extensive treatment for relapsed or hard-to-treat B cell precursor acute lymphoblastic leukemia (R/R B-ALL). While some side effects occurred, most patients managed them well.

Another study examined the safety and pharmacokinetics of under-the-skin blinatumomab in adults with R/R B-ALL. The results were promising, indicating that patients generally tolerated it well.

Blincyto, the brand name for blinatumomab, has already received FDA approval for certain uses. This suggests safety when used as directed, although the under-the-skin form is still under study to confirm these findings.

Overall, while research continues, early studies suggest the treatment is generally well-tolerated, with manageable side effects for most patients. ^{1 2 3 4 5}

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

Blinatumomab is unique because it employs a novel mechanism of action as a bispecific T-cell engager (BiTE) that helps the immune system fight cancer cells directly. Unlike standard treatments for acute lymphoblastic leukemia (ALL), such as chemotherapy, blinatumomab specifically targets and binds to both T-cells and cancer cells, facilitating the immune system’s ability to attack the leukemia cells. Researchers are also excited about the subcutaneous (SC) formulation of blinatumomab, which may offer a more convenient administration method compared to the traditional intravenous delivery, potentially improving patient comfort and compliance. This innovative approach not only aims to enhance treatment effectiveness but also strives to minimize side effects typically associated with conventional therapies.

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

Research has shown that blinatumomab may effectively treat Acute Lymphoblastic Leukemia (ALL). In earlier studies, about 78% of patients had no detectable cancer cells after just one treatment cycle. Additionally, 39% of patients who received the recommended dose experienced complete symptom disappearance. This trial will evaluate different formulations and dosing strategies of blinatumomab in various treatment arms. These findings suggest that blinatumomab can successfully target and reduce cancer cells in people with this type of leukemia. Overall, the treatment appears to offer strong potential for those whose B-cell precursor ALL has returned or is not responding to other treatments. ^{6 7 8 9 10}

Who Is on the Research Team?

MD

Principal Investigator

Amgen

Are You a Good Fit for This Trial?

This trial is for adults with B-precursor Acute Lymphoblastic Leukemia (ALL) who may have relapsed after stem cell transplant, have a certain percentage of cancer cells in their bone marrow, or are not responding to other treatments. It's open to those with an ECOG Performance Status of 2 or less and includes patients intolerant to tyrosine kinase inhibitors.

Inclusion Criteria

I have B-precursor acute lymphoblastic leukemia.

My condition is in its first or later relapse and has not been treated yet.

My disease did not fully respond to the initial treatment.

Exclusion Criteria

- Currently receiving treatment in, or less than 30 days since ending treatment on another investigational study(ies)

I have leukemia in my brain or spinal cord.

I had a stem cell transplant from a donor within the last 12 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Cohorts of at least 3 participants each will be treated with escalating doses of blinatumomab to determine the maximum tolerated dose (MTD). Safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy will be assessed.

8-12 weeks

Dose Expansion

Up to 4 cohorts of participants with R/R B-ALL will be enrolled to the preliminary recommended phase 2 dose (RP2D) and schedule determined from dose escalation phase. Each cohort will aim to further assess safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy.

12-16 weeks

Clinical PK Evaluation

The clinical PK evaluation cohort (Ph-IIC) will be conducted to compare the PK of SC1 and SC2 formulations at the RP2D determined from the dose expansion phase, in participants with R/R B-ALL.

4-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab

Trial Overview The study tests the safety and effectiveness of Blinatumomab given under the skin for treating ALL. It aims to find the highest dose patients can tolerate without severe side effects and establish recommended doses for future phases. The trial also examines how the body processes this drug.

How Is the Trial Designed?

Group I: Ph-IIR: Efficacy of SC Blinatumomab in Participants with R/R B-ALL Experimental Treatment 1 Intervention

The efficacy of SC blinatumomab (in the SC2 formulation) will be evaluated in adults and adolescents with R/R B-ALL.

Group II: Ph-IIM: Efficacy of SC Blinatumomab in Participants with MRD+ B-ALL Experimental Treatment 1 Intervention

The efficacy of SC blinatumomab (in the SC2 formulation) will be evaluated in adults and adolescents with MRD+ B-ALL.

Group III: Ph-IIC: Clinical PK Evaluation of SC Blinatumomab Formulations Experimental Treatment 1 Intervention

1 cohort of adult participants will be enrolled into the Ph-IIC arm. The clinical PK evaluation cohort (Ph-IIC) will be conducted to compare the PK of SC1 and SC2 formulations at the preliminary RP2D determined from the dose expansion phase, in participants with R/R B-ALL.

Group IV: Dose Expansion Phase: Blinatumomab SC1 Experimental Treatment 1 Intervention

Up to 4 cohorts of adult participants with R/R B-ALL will be enrolled at different dose levels to support identification of the RP2D. Each cohort will aim to further assess safety, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy.

Group V: Dose Escalation Phase: Blinatumomab Subcutaneous Formulation 1 (SC1) Experimental Treatment 1 Intervention

Cohorts of at least 3 adult participants with R/R B-ALL will be treated with escalating doses of blinatumomab to determine the maximum tolerated dose (MTD). The MTD will be defined as the dose for which the estimate of the toxicity rate from an isotonic regression (Yan et al, 2017) is closest to the target toxicity rate. Safety, pharmacokinetics (PK), pharmacodynamics (PD) and efficacy will be assessed.

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?

Amgen

Lead 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

BeiGene

Industry Sponsor

Trials

216

Recruited

32,500+

BeOne Medicines

Industry Sponsor

Published Research Related to This Trial

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 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]

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]

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 (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]

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, 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]

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]

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]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2352302625001449

Subcutaneous blinatumomab in adults with relapsed or ... Treatment with subcutaneous blinatumomab at the two dose regimens of 250 μg/500 μg and 500 μg/1000 μg resulted in promising preliminary activity and a ...

2. thelancet.com thelancet.com/journals/lanhae/article/PIIS2352-3026(25)00144-9/abstract

Subcutaneous blinatumomab in adults with relapsed or ... Patients received between two and five cycles. The primary endpoint for the dose-expansion phase was complete remission or complete remission ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT07134088

A Study of Subcutaneous Blinatumomab in Children With R ... The main objective of this study is to evaluate the safety and efficacy of SC blinatumomab in children below 12 years of age. Official Title. A ...

4. aob.amegroups.org aob.amegroups.org/article/view/11031/html

Immunotherapy with blinatumomab in B-cell acute ... Overall, 78% of patients achieved MRD negativity after one cycle of blinatumomab (18). TOWER (NCT02013167), a phase III study, further explored ...

5. ashpublications.org ashpublications.org/bloodadvances/article/9/15/3946/537699/Blinatumomab-use-in-pediatric-B-ALL-where-are-we

Blinatumomab use in pediatric B-ALL: where are we now? Among 70 patients who received the recommended dosage, 27 (39%) achieved a complete remission (CR; defined as no circulating blasts or ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2018/125557s013lbl.pdf

BLINCYTO® (blinatumomab) for injection - accessdata.fda.gov The safety data described below reflect exposure to BLINCYTO in a randomized, open-label, active-controlled clinical study (TOWER Study) in which 376 patients ...

7. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/6122/488037/Safety-and-Pharmacokinetics-of-Subcutaneous

Safety and Pharmacokinetics of Subcutaneous Blinatumomab ... Safety and pharmacokinetics of subcutaneous blinatumomab (SC blinatumomab) for the treatment of adults with relapsed or refractory B cell precursor acute ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT04521231

NCT04521231 | A Study of Subcutaneous Blinatumomab ... The Phase II part of the study will evaluate the safety, efficacy, and tolerability of SC blinatumomab for treatment of R/R B-ALL and Minimum Residual Disease ...

9. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38317420/

Single agent subcutaneous blinatumomab for advanced ... Treatment with SC blinatumomab resulted in high efficacy, with high MRD-negativity rates and acceptable safety profile in heavily pretreated adults with R/R B- ...

10. sciencedirect.com sciencedirect.com/science/article/pii/S0006497121042543

Safety and Efficacy of Subcutaneous (SC) Blinatumomab ... In this phase 1b dose-finding study, SC blinatumomab has demonstrated encouraging anti-leukemia activity in heavily pretreated patients with R/R B-ALL.