Blinatumomab for Acute Lymphoblastic Leukemia
Recruiting in Palo Alto (17 mi)
+59 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Waitlist Available
Sponsor: Amgen
No Placebo Group
Breakthrough Therapy
Approved in 2 jurisdictions
Trial Summary
What is the purpose of this trial?The study aims to evaluate the safety, efficacy, and tolerability of subcutaneous (SC) blinatumomab for treatment of Acute Lymphoblastic Leukemia (ALL), to determine the maximum tolerated dose (MTD), and recommended phase 2 dose(s) (RP2D) of SC administered blinatumomab. It will also conduct a clinical PK evaluation of SC1 and SC2 blinatumomab formulations.
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.
What data supports the idea that Blinatumomab for Acute Lymphoblastic Leukemia (also known as: Blinatumomab, Blincyto) is an effective drug?
The available research shows that Blinatumomab is effective for treating Acute Lymphoblastic Leukemia (ALL), especially in cases where the disease has returned or is not responding to other treatments. It works by activating the body's immune system to attack cancer cells. Studies have shown that it can lead to deep remissions, meaning a significant reduction in cancer cells, in some patients. Compared to older treatments, which often had limited success and more side effects, Blinatumomab offers a new approach with better outcomes for some patients. However, not all patients respond to the drug, and some may experience a return of the disease, indicating that further improvements are needed.
12345What safety data is available for Blinatumomab in treating acute lymphoblastic leukemia?
Blinatumomab, also known as Blincyto, has been associated with serious adverse events such as cytokine release syndrome (CRS) and neurologic events, including seizures and encephalopathy. Grade 3 or 4 adverse effects are common. Despite these risks, most patients tolerate the therapy relatively well. Safety data has been evaluated in both pediatric and adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia.
678910Is the drug Blinatumomab a promising treatment for Acute Lymphoblastic Leukemia?
Yes, Blinatumomab is a promising drug for treating Acute Lymphoblastic Leukemia. It has been effective in helping some patients achieve complete remission, meaning their cancer symptoms disappear. It has received approval for use in both adults and children, showing its potential to help people with this aggressive type of cancer.
58111213Eligibility Criteria
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 am 18 years old or older.
I have B-precursor acute lymphoblastic leukemia.
My condition is in its first or later relapse and has not been treated yet.
+11 more
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.
+7 more
Participant Groups
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.
3Treatment groups
Experimental Treatment
Group I: Ph-IIC: Clinical PK Evaluation of SC Blinatumomab FormulationsExperimental Treatment1 Intervention
1 cohort of 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 RP2D determined from the dose expansion phase, in participants with R/R B-ALL.
Group II: Dose Expansion Phase: Blinatumomab SC1Experimental Treatment1 Intervention
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.
Group III: Dose Escalation Phase: Blinatumomab Subcutaneous Formulation 1 (SC1)Experimental Treatment1 Intervention
Cohorts of at least 3 participants each will be treated with escalating doses of bilinatumomab 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
New York University Grossman School of Medicine and New York University Langone HospitalsNew York, NY
Princess Margaret Cancer CentreToronto, Canada
University of AlbertaEdmonton, Canada
Tom Baker Cancer CentreCalgary, Canada
More Trial Locations
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Who Is Running the Clinical Trial?
AmgenLead Sponsor
References
Blinatumomab: enlisting serial killer T-cells in the war against hematologic malignancies. [2023]The approval of blinatumomab signals the long awaited arrival of immunotherapy for acute lymphoblastic leukemia (ALL). Previous options for relapsed or refractory disease were restricted to cytotoxic chemotherapy with limited efficacy and significant toxicity. Through an innovative mechanism of action, blinatumomab stimulates a polyclonal antitumor T-cell response, yielding unprecedented single agent efficacy in the relapsed/refractory setting. Success comes at the cost of immunological toxicities rarely encountered with previous therapies and challenging administration logistics requiring clinical expertise.
Bispecific antibodies in acute lymphoblastic leukemia therapy. [2021]Blinatumomab, first in a class of bispecific T-cell engagers, revolutionized treatment paradigm of B-cell precursor relapsed/refractory or minimal residual disease positive acute lymphoblastic leukemia (ALL) in adults and children, inducing deep remissions in a proportion of patients. However, significant numbers of patients do not respond or eventually relapse. Strategies for improvement of treatment outcomes are required.
[Safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia]. [2023]To study the safety and short-term effectiveness of blinatumomab in the treatment of childhood relapsed/refractory acute lymphoblastic leukemia (R/R-ALL).
Immunoglobulin repletion during blinatumomab therapy does not reduce the rate of secondary hypogammaglobulinemia and associated infectious risk. [2022]Blinatumomab has demonstrated efficacy in minimal residual disease (MRD) positive and relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) by inciting rapid and sustained B-cell depletion.
A Systematic Review of Blinatumomab in the Treatment of Acute Lymphoblastic Leukemia: Engaging an Old Problem With New Solutions. [2021]To assess the current literature for blinatumomab in the treatment of adult and pediatric B-cell acute lymphoblastic leukemia (ALL).
Efficacy and Safety of Blinatumomab for the Treatment of Relapsed/Refractory Acute Lymphoblastic Leukemia: A Systemic Review and Meta-Analysis. [2023]The aim was to evaluate the efficacy and safety of blinatumomab monotherapy for the treatment of relapsed/refractory acute lymphoblastic leukemia (R/R B-ALL).
Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults. [2022]Adults with relapsed or refractory B-cell acute lymphoblastic leukemia have a dismal prognosis with a short median overall survival that can be measured in months. Because most patients will have chemotherapy-resistant disease, allogeneic hematopoietic stem cell transplantation remains the only potentially curative treatment. Despite advances in current management, patients continue to have poor outcomes and lack of durable responses. Thus, new therapies with alternative modes of actions are currently being investigated. Blinatumomab is a novel bispecific T-cell engager that simultaneously binds CD3-positive cytotoxic T-cells and CD19-positive B-cells, resulting in selective lysis of tumor cells. It has shown promising results in patients with relapsed or refractory acute lymphoblastic leukemia or those achieving hematologic response with persistent minimum residual disease. Future clinical trials will answer questions regarding its optimal place in the treatment paradigm. Dose-limiting toxicities include immunological toxicities and cytokine release syndrome. However, most patients tolerate the therapy relatively well. This review will focus on the pharmacology, clinical efficacy, and safety of blinatumomab in the treatment of adult B-cell acute lymphoblastic leukemia while highlighting its unique drug warnings and toxicity management.
Blinatumomab (Blincyto) for acute lymphoblastic leukemia. [2015]Blinatumomab (Blincyto) was effective in inducing a complete remission in 33% of patients with relapsed or refractory Philadelphia chromosome-negative (Ph-) B-cell precursor acute lymphoblastic leukemia (ALL). Grade 3 or 4 adverse effects occur frequently.
Blinatumomab: A First-in-Class Bispecific T-Cell Engager for Precursor B-Cell Acute Lymphoblastic Leukemia. [2018]To review the clinical pharmacology, efficacy, and safety of blinatumomab for the treatment of pediatric and adult precursor B-cell acute lymphoblastic leukemia (B-ALL).
The safety of blinatumomab in pediatric patients with acute lymphoblastic leukemia: A systematic review and meta-analysis. [2022]Blinatumomab is a bispecific CD19-directed CD3 T-cell engager that has proven efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL). Despite its efficacy, it has also been associated with the development of potentially serious adverse events such as the cytokine release syndrome (CRS) and neurologic events. The present meta-analysis aimed to assess the safety profile of blinatumomab in terms of serious adverse events, CRS, and neurologic events (such as seizure and encephalopathy) in pediatric patients with B-cell ALL.
A closer look at blinatumomab. [2018]On March 29, 2018, blinatumomab (Blincyto, Amgen) received an accelerated expanded approval for the treatment of adult and pediatric patients with B-cell precursor acute lymphoblastic leukemia (ALL) who are in first or second complete remission (CR) and have minimal residual disease (MRD). Blinatumomab was first approved for use in adult patients (in December 2014) and later in pediatric patients (in September 2016) with relapsed or refractory Philadelphia chromosome (Ph)-negative B-cell precursor ALL; the approval was expanded in July 2017 to include patients with Ph-positive disease. The agent is a bispecific CD19-directed CD3 T-cell engager.
Estimating Long-Term Survival of Adults with Philadelphia Chromosome-Negative Relapsed/Refractory B-Precursor Acute Lymphoblastic Leukemia Treated with Blinatumomab Using Historical Data. [2021]Blinatumomab is a bispecific T cell-engaging antibody construct indicated for adult patients with relapsed/refractory (R/R) Ph(-) B-precursor acute lymphoblastic leukemia (ALL), an aggressive disease with poor prognosis. A phase 2 single-arm clinical study showed that 43% of patients achieved CR/CRh within two cycles and approximately 20% of patients receiving blinatumomab were still alive after 2 years.
A Multidisciplinary Approach to Standardizing Processes for Blinatumomab Administration. [2017]Blinatumomab (Blincyto®) has received accelerated approval for treatment of relapsed or refractory acute lymphoblastic leukemia. This article describes the authors' experience with a multidisciplinary collaboration among nursing, pharmacy, prescribers, and support staff, which has proven to be key for safe administration. The approach can be applied to other institutions planning to use blinatumomab.