Pembrolizumab + Blinatumomab for Acute Lymphoblastic Leukemia
Recruiting in Palo Alto (17 mi)
Overseen ByLihua Budde
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: City of Hope Medical Center
Must not be taking: Antidepressants, Immunosuppressants
Disqualifiers: CNS disease, Organ transplantation, Autoimmune, others
No Placebo Group
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase I/II studies the side effects of pembrolizumab and blinatumomab and to see how well they work in treating participants with acute lymphoblastic leukemia that has come back or has not responded to the treatment. Monoclonal antibodies, such as pembrolizumab and blinatumomab, may interfere with the ability of tumor cells to grow and spread.
Will I have to stop taking my current medications?
The trial requires participants to stop taking certain cancer treatments before starting the study. You must stop chemotherapy, radiotherapy, tyrosine-kinase inhibitors, and immunotherapy at least 1 week or 5 half-lives before the study begins. Some maintenance medications for ALL, like glucocorticoids, can be taken up to 3 days before the study, but others like vinca alkaloids must be stopped 14 days prior.
What data supports the effectiveness of the drug pembrolizumab in treating cancer?
Pembrolizumab has been shown to improve survival in patients with certain types of lung cancer, as it helps the immune system attack cancer cells more effectively. It has been approved for use in advanced melanoma and non-small cell lung cancer, demonstrating significant improvements in survival compared to chemotherapy.
12345Is the combination of Pembrolizumab and Blinatumomab safe for humans?
Blinatumomab, used for certain types of leukemia, generally has a favorable safety profile, but it can cause side effects like cytokine-release syndrome (a reaction that can cause fever and low blood pressure) and neurological issues (like seizures), which are usually manageable with treatment. Pembrolizumab, used in various cancers, is also generally considered safe but can cause immune-related side effects. While specific safety data for the combination of these drugs is not provided, both have been used safely in humans for other conditions.
678910How is the drug combination of Pembrolizumab and Blinatumomab unique for treating acute lymphoblastic leukemia?
This drug combination is unique because it combines Pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells, with Blinatumomab, a bispecific T-cell engager that directs T-cells to target and destroy leukemia cells. This dual approach aims to enhance the immune response against leukemia, potentially offering a novel treatment option for patients who do not respond to standard therapies.
78111213Eligibility Criteria
This trial is for people with acute lymphoblastic leukemia that's come back or didn't respond to treatment. They must have had prior treatments, be relatively healthy and active (ECOG status 0-1), have good heart and lung function, normal kidney and liver tests, not pregnant or breastfeeding, no HIV/HBV/HCV infections, and willing to use contraception.Inclusion Criteria
Ability to understand and sign informed consent form
My kidney function, measured by creatinine levels, is within the normal range.
Beta HCG negative
+23 more
Exclusion Criteria
Concurrent participation in another investigational drug trial
Current participation in or recent completion of another investigational study
Psychiatric or substance abuse disorders
+16 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive pembrolizumab IV on day 15 of cycle 1 and days 1 and 22 of cycles 2-5, and blinatumomab IV on days 1-28. Treatment repeats every 35-42 days for up to 5 cycles.
35-42 days per cycle, up to 5 cycles
Optional Extension
Patients who achieve complete response have the option to receive blinatumomab IV for up to 4 additional cycles.
Up to 4 cycles
Follow-up
Participants are monitored for safety and effectiveness after treatment completion.
1 year
Follow-up at 30 days, then every 3 months
Participant Groups
The study is testing the effectiveness of two monoclonal antibodies—pembrolizumab and blinatumomab—in treating recurrent or unresponsive acute lymphoblastic leukemia. It aims to see how these drugs affect tumor growth.
1Treatment groups
Experimental Treatment
Group I: Treatment (pembrolizumab, blinatumomab)Experimental Treatment3 Interventions
Participants receive pembrolizumab IV over 30 minutes on day 15 of course 1 and days 1 and 22 of courses 2 -4, and blinatumomab IV on days 1-28. Treatment repeats every 35-42 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
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:
City of Hope Medical CenterDuarte, CA
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Who Is Running the Clinical Trial?
City of Hope Medical CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]A phase II trial investigating the therapeutic effect of neoadjuvant programmed cell death 1 (PD-1) inhibitor pembrolizumab (MK-3475, KEYTRUDA®) administered prior to surgery for the treatment of non-small cell lung cancer (NSCLC) has been conducted (NCT03197467). We report the first clinical results of a planned interim safety analysis after 15 patients were enrolled.
FDA Approval Summary: Pembrolizumab for Treatment of Metastatic Non-Small Cell Lung Cancer: First-Line Therapy and Beyond. [2022]On October 24, 2016, the U.S. Food and Drug Administration (FDA) approved pembrolizumab (Keytruda; Merck & Co., Inc., https://www.merck.com) for treatment of patients with metastatic non-small cell lung cancer (mNSCLC) whose tumors express programmed death-ligand 1 (PD-L1) as determined by an FDA-approved test, as follows: (a) first-line treatment of patients with mNSCLC whose tumors have high PD-L1 expression (tumor proportion score [TPS] ≥50%), with no epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) genomic tumor aberrations, and (b) treatment of patients with mNSCLC whose tumors express PD-L1 (TPS ≥1%), with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving pembrolizumab.Approval was based on two randomized, open-label, active-controlled trials demonstrating statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients randomized to pembrolizumab compared with chemotherapy. In KEYNOTE-024, patients with previously untreated mNSCLC who received pembrolizumab (200 mg intravenously [IV] every 3 weeks) had a statistically significant improvement in OS (hazard ratio [HR] 0.60; 95% confidence interval [CI]: 0.41-0.89; p = .005), and significant improvement in PFS (HR 0.50; 95% CI: 0.37-0.68; p < .001). In KEYNOTE-010, patients with disease progression on or after platinum-containing chemotherapy received pembrolizumab IV 2 mg/kg, 10 mg/kg, or docetaxel 75 mg/m2 every 3 weeks. The HR and p value for OS was 0.71 (95% CI: 0.58-0.88), p < .001 comparing pembrolizumab 2 mg/kg with chemotherapy and the HR and p value for OS was 0.61 (95% CI: 0.49-0.75), p < .001 comparing pembrolizumab 10 mg/kg with chemotherapy.
Pembrolizumab for Patients with Relapsed or Refractory Extranodal NK/T-Cell Lymphoma in Korea. [2023]PD-1 blockade with pembrolizumab has shown promising activity in relapsed/refractory (R/R) extranodal natural killer (NK)/T-cell lymphoma (NKTCL), but studies are limited, with small patient numbers.
Pembrolizumab for the treatment of PD-L1 positive advanced or metastatic non-small cell lung cancer. [2020]The emergence of immune checkpoint inhibitors marked an important advancement in the development of cancer therapeutics. Pembrolizumab is a selective humanized IgG4 kappa monoclonal antibody that inhibits the programmed death-1 (PD-1) receptor, an integral component of immune checkpoint regulation in the tumor microenvironment. The drug is currently approved by the Food and Drug Administration for the treatment of advanced melanoma and metastatic squamous and nonsquamous non-small cell lung cancer (NSCLC). Several published studies demonstrate that single-agent pembrolizumab is safe and has efficacy in patients with NSCLC. Many ongoing protocols are investigating the role of pembrolizumab in combination with other agents in lung cancer and various other cancer types. We review the available data on pembrolizumab in NSCLC and examine the role of potential predictive biomarkers of response to therapy.
KEYNOTE-022: Pembrolizumab with trametinib in patients with BRAF wild-type melanoma or advanced solid tumours irrespective of BRAF mutation. [2022]Parts 4 and 5 of the phase 1/2 KEYNOTE-022 study investigated the maximum tolerated dose (MTD), safety, and efficacy of pembrolizumab plus trametinib in solid tumours and BRAF wild-type melanoma.
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).
Effect of Postreinduction Therapy Consolidation With Blinatumomab vs Chemotherapy on Disease-Free Survival in Children, Adolescents, and Young Adults With First Relapse of B-Cell Acute Lymphoblastic Leukemia: A Randomized Clinical Trial. [2021]Standard chemotherapy for first relapse of B-cell acute lymphoblastic leukemia (B-ALL) in children, adolescents, and young adults is associated with high rates of severe toxicities, subsequent relapse, and death, especially for patients with early relapse (high risk) or late relapse with residual disease after reinduction chemotherapy (intermediate risk). Blinatumomab, a bispecific CD3 to CD19 T cell-engaging antibody construct, is efficacious in relapsed/refractory B-ALL and has a favorable toxicity profile.
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).
Immunotargeting relapsed or refractory precursor B-cell acute lymphoblastic leukemia - role of blinatumomab. [2020]Patients with refractory or relapsed (R/R) acute lymphoblastic leukemia (ALL) have a dismal prognosis of around 5% long-term survival when treated with cytotoxic chemotherapy and allogenic stem cell transplantation. T-cell immunobased strategies open up new therapeutic perspectives. Blinatumomab is the first of a new class of antibody constructs that was labeled bispecific T-cell engager (BiTE): it consists of two single chain variable fragment connected with a flexible linker, one side binding CD3, the other CD19. The tight binding and the close proximity to the CD19-positive B-cells and leukemic cells leads to non-major histocompatibility complex-restricted T-cell activation, polyclonal T-cell expansion and direct target cell killing. Applied by continuous infusion, blinatumomab achieves morphological complete response rates ranging from 39% to 69% in R/R ALL patients (compared to 25% after second-line chemotherapy) with prolonged overall survival (blinatumomab median overall survival, 7.7 months vs chemotherapy, 4.0 months). In comparison to conventional cytotoxic second-line protocols blinatumomab has a favorable safety profile. The main adverse event is related to the mode of action of blinatumomab: the induction of a cytokine-release syndrome that can be managed by interruption and/or the application of steroids or tocilizumab. Another typical complication is the occurrence of neurological side effects, such as seizures and encephalopathy. This neurotoxicity is reversible after application of steroids and/or withdrawal of blinatumomab. Blinatumomab has proven to be a powerful therapeutic option in R/R ALL patients both adult and pediatric because of its efficacy and limited toxicity.
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.
Changes in clinical laboratory parameters and pharmacodynamic markers in response to blinatumomab treatment of patients with relapsed/refractory ALL. [2022]Blinatumomab has shown a remission rate of 69% in an exploratory single-arm, phase II dose-escalation study in adult patients with relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL). We evaluated changes in laboratory parameters and immunopharmacodynamic markers in patients who received blinatumomab in the exploratory phase II study.
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.