Calaspargase Pegol for Acute Lymphoblastic Leukemia
Recruiting in Palo Alto (17 mi)
+23 other locations
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Waitlist Available
Sponsor: Institut de Recherches Internationales Servier
No Placebo Group
Prior Safety Data
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?This trial is testing Calaspargase pegol, a medication for treating a specific type of blood cancer called Philadelphia-negative Acute Lymphoblastic Leukemia. The study aims to find the best dose and check the safety of the drug. Calaspargase pegol works by starving the cancer cells of a nutrient they need to survive.
Do I have to stop taking my current medications for this trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have had prior therapy for ALL, except for limited corticosteroids or hydroxyurea treatment and a single dose of intrathecal cytarabine.
What data supports the idea that Calaspargase Pegol for Acute Lymphoblastic Leukemia is an effective drug?
The available research shows that Calaspargase Pegol is effective in treating Acute Lymphoblastic Leukemia (ALL) in children and young adults. It was approved by the FDA based on its ability to maintain necessary enzyme levels in the blood, which is crucial for successful treatment. In a study, 99% of patients maintained these levels over several weeks, indicating its effectiveness. Additionally, when compared to another drug, Pegaspargase, Calaspargase Pegol had a similar safety profile and did not negatively impact the patients' chances of staying free from the disease.
12345What safety data is available for Calaspargase Pegol in treating Acute Lymphoblastic Leukemia?
Calaspargase Pegol, approved by the FDA in December 2018 for treating acute lymphoblastic leukemia (ALL) in children and young adults, has been evaluated for safety in several studies. The Dana-Farber Cancer Institute Protocol 11-001 compared its efficacy and toxicity to pegaspargase, showing a similar safety profile. The Children's Oncology Group Study AALL07P4 also assessed its pharmacokinetics and pharmacodynamics, confirming its comparability to pegaspargase. The FDA approval was based on maintaining steady-state nadir serum asparaginase activity, with no substantial impairment in event-free survival compared to pegaspargase. Overall, Calaspargase Pegol has demonstrated a safety profile similar to existing treatments.
12346Is the drug Calaspargase pegol a promising treatment for Acute Lymphoblastic Leukemia?
Yes, Calaspargase pegol is a promising drug for treating Acute Lymphoblastic Leukemia. It has been approved by the FDA for use in children and young adults, showing similar safety and effectiveness compared to existing treatments. It has a longer-lasting effect, which means it can be given less frequently, making it more convenient for patients.
12347Eligibility Criteria
Adults aged 22 or older with newly-diagnosed Philadelphia-negative Acute Lymphoblastic Leukemia (ALL) can join this trial. They should be relatively active and able to care for themselves (ECOG PS 0-2). Prior limited treatment for ALL is okay, but those with certain other leukemias, Down syndrome, hepatitis B or C, HIV-positive status, a history of pancreatitis not caused by gallstones, or severe liver issues cannot participate.Inclusion Criteria
I haven't had treatment for ALL except possibly short-term steroids, hydroxyurea, or a single dose of intrathecal cytarabine.
I can take care of myself and am up and about more than half of my waking hours.
I am 22 or older with a new diagnosis of a specific type of leukemia that is not Philadelphia chromosome positive.
Exclusion Criteria
I have had pancreatitis not caused by gallstones.
Participants known to be HIV-positive.
Patients with Hepatitis B (positive for HBs antigen), and Hepatitis C (HCV antibody) at inclusion.
+3 more
Participant Groups
This phase 2/3 study tests Calaspargase pegol's safety and how the body responds to it in adults with Philadelphia-negative ALL. The goal is to confirm proper dosing levels for effective treatment.
1Treatment groups
Experimental Treatment
Group I: Calaspargase pegol (S95015)Experimental Treatment1 Intervention
Calaspargase pegol is already approved in United States for the following indications:
🇺🇸 Approved in United States as Asparlas for:
- Acute Lymphoblastic Leukemia (ALL) in pediatric and young adult patients aged one month to 21 years
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Dana Farber Cancer InstituteWeymouth, MA
Northwell Health Cancer InstituteLake Success, NY
Oregon Health & Science University (OHSU)Portland, OR
Intermountain Healthcare (IHC)Salt Lake City, UT
More Trial Locations
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Who Is Running the Clinical Trial?
Institut de Recherches Internationales ServierLead Sponsor
ADIR, a Servier Group companyIndustry Sponsor
References
Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001. [2021]Dana-Farber Cancer Institute Acute Lymphoblastic Leukemia (ALL) Consortium Protocol 11-001 assessed efficacy and toxicity of calaspargase pegol (calaspargase), a novel pegylated asparaginase formulation with longer half-life, compared with the standard formulation pegaspargase.
Pharmacokinetic and pharmacodynamic properties of calaspargase pegol Escherichia coli L-asparaginase in the treatment of patients with acute lymphoblastic leukemia: results from Children's Oncology Group Study AALL07P4. [2021]Asparaginase is a critical agent used to treat acute lymphoblastic leukemia (ALL). Pegaspargase (SS-PEG), a pegylated form of Escherichia coli L-asparaginase with a succinimidyl succinate (SS) linker, is the first-line asparaginase product used in Children's Oncology Group (COG) ALL trials. Calaspargase pegol (SC-PEG) replaces the SS linker in SS-PEG with a succinimidyl carbamate linker, creating a more stable molecule. COG AALL07P4 was designed to determine the pharmacokinetic and pharmacodynamic comparability of SC-PEG to SS-PEG in patients with newly diagnosed high-risk (HR) B-cell ALL.
FDA Approval Summary: Calaspargase Pegol-mknl For Treatment of Acute Lymphoblastic Leukemia in Children and Young Adults. [2020]On December 20, 2018, the Food and Drug Administration approved calaspargase pegol-mknl (CALASP), an asparagine-specific enzyme, as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia (ALL) in pediatric and young adult patients age 1 month to 21 years. Efficacy was determined on the basis of achievement and maintenance of steady-state nadir serum asparaginase activity (NSAA) above 0.1 U/mL when using CALASP, 2,500 U/m2 intravenously, every 3 weeks. In a randomized comparison to pegaspargase (PEGASP) every 2 weeks, treatment with CALASP every 3 weeks had a similar safety profile and no substantial impairment in event-free survival. The pharmacokinetics of CALASP were studied when administered in combination with multiagent chemotherapy in 124 patients with B-cell ALL in Study AALL07P4 and Study DFCI 11-001. The results showed that 123 [99%, 95% confidence interval (CI), 96%-100%] of the 124 patients maintained NSAA >0.1 U/mL at weeks 6, 12, 18, 24, and 30 of post-induction phase. Maintaining adequate NSAA levels is critical to successful treatment of ALL. Herein, we describe the FDA review and approval of CALASP.See related commentary by Lew, p. 325.
Space for Calaspargase? A New Asparaginase for Acute Lymphoblastic Leukemia. [2020]In December 2018, the FDA approved calaspargase pegol-mknl (Asperlas, Servier Pharmaceuticals) for acute lymphoblastic leukemia (ALL) in children and young adults up to age 21. Asparaginase is a critical component in the treatment of ALL, but the niche for calaspargase within current treatment protocols is unclear.See related article by Li et al., p. 328.
Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511. [2021]CALGB 9511 used pegaspargase (PEG-ASP) in lieu of the native enzyme. The aim was to compare differences in overall survival (OS) and disease-free survival (DFS) between patients who did and did not achieve asparagine depletion, defined by enzyme levels greater than 0.03 U/mL plasma for 14 consecutive days after at least 1 of 4 planned PEG-ASP administrations. Samples were available from 85 eligible patients. On univariate analyses, the 22 patients who did not achieve asparagine depletion had inferior OS (P = .002; hazard ratio [HR] = 2.37; 95% CI = 1.38-4.09) and DFS (P = .012; HR = 2.21; 95% CI = 1.19-4.13). After adjusting for age, performance status, leukocyte count, and karyotype in a proportional hazards model, both the OS and DFS HRs decreased to 1.8 (P = .056; 95% CI = 1.0-3.2 and P = .084; 95% CI = 0.9-3.6, respectively). We conclude that effective asparagine depletion with PEG-ASP is feasible as part of an intensive multiagent therapeutic regimen in adult acute lymphoblastic leukemia and appears associated with improved outcomes.
Experience with generic pegylated L-asparaginase in children with acute lymphoblastic leukemia and monitoring of serum asparaginase activity. [2019]Pegylated asparaginase (P-Asp) though integral to acute lymphoblastic leukemia (ALL) therapy is often not accessible to patients in developing countries. We share our clinical experience with generic P-Asp along with monitoring of asparaginase activity.
Intravenous pegylated asparaginase versus intramuscular native Escherichia coli L-asparaginase in newly diagnosed childhood acute lymphoblastic leukaemia (DFCI 05-001): a randomised, open-label phase 3 trial. [2022]l-asparaginase is a universal component of treatment for childhood acute lymphoblastic leukaemia, and is usually administered intramuscularly. Pegylated Escherichia coli asparaginase (PEG-asparaginase) has a longer half-life and is potentially less immunogenic than the native Escherichia coli (E coli) preparation, and can be more feasibly administered intravenously. The aim of the Dana-Farber Cancer Institute Acute Lymphoblastic Leukaemia Consortium Protocol 05-001 (DFCI 05-001) was to compare the relative toxicity and efficacy of intravenous PEG-asparaginase and intramuscular native E colil-asparaginase in children with newly diagnosed acute lymphoblastic leukaemia.