Calaspargase Pegol for Acute Lymphoblastic Leukemia

Recruiting at 23 trial locations

Overseen By Institut de Recherches Internationales Servier, Clinical Studies Department

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Institut de Recherches Internationales Servier

Disqualifiers: Philadelphia-positive ALL, Down syndrome, Hepatitis B/C, HIV, 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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 410

122 Participants Needed

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.

Will I have to stop taking my current medications?

The trial protocol does not specify whether you need to stop taking your current medications. However, it mentions that you should not have had prior therapy for ALL, except for limited treatment with corticosteroids or hydroxyurea.

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. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Calaspargase Pegol for treating Acute Lymphoblastic Leukemia?

Calaspargase Pegol has been shown to maintain necessary enzyme activity levels in nearly all patients, which is important for treating Acute Lymphoblastic Leukemia (ALL). It has a similar safety profile to another standard treatment, Pegaspargase, and does not negatively impact event-free survival, making it an effective option for children and young adults with ALL. ^{1 2 3 4 6}

What 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. ^{1 2 3 4 7}

Is calaspargase pegol safe for use in humans?

Calaspargase pegol has been approved by the FDA for treating acute lymphoblastic leukemia in children and young adults, and studies show it has a similar safety profile to the standard treatment, pegaspargase. This means it is generally considered safe when used as part of a multi-drug treatment plan for this condition. ^{1 2 3 4 7}

Is 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. ^{1 2 3 4 8}

How is the drug Calaspargase Pegol different from other treatments for acute lymphoblastic leukemia?

Calaspargase Pegol is unique because it has a longer half-life than the standard pegaspargase, meaning it stays active in the body longer, allowing for less frequent dosing (every 3 weeks instead of every 2 weeks). It also uses a different chemical linker, making it more stable. ^{1 2 3 4 8}

Research Team

Daniel DeAngelo, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute, Boston, MA

Eligibility 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.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Remission Induction

Participants receive Calaspargase pegol to induce remission

4 weeks

Multiple visits on Days 4, 5, 6, 11, 18, 25

Remission Consolidation

Participants continue treatment to consolidate remission

8 weeks

Visits on Days 15, 16, 43, 44, 22, 29, 36, 50, 57, 64

Interim Maintenance

Participants receive maintenance therapy to sustain remission

4 weeks

Visits on Days 22, 23, 29, 36, 43

Delayed Intensification

Participants undergo intensified treatment to prevent relapse

8 weeks

Visits on Days 4, 5, 43, 44, 11, 18, 25, 50, 57, 64

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Day 365 after the first dose, Day 30 after the last dose if discontinuation

Treatment Details

Interventions

• Calaspargase pegol

Trial Overview 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.

Participant Groups

Group I: Calaspargase pegol (S95015) Experimental Treatment 1 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

Who Is Running the Clinical Trial?

Institut de Recherches Internationales Servier

Lead Sponsor

Trials

91

Recruited

67,100+

ADIR, a Servier Group company

Industry Sponsor

Trials

33

Recruited

4,300+

Findings from Research

In a study involving 239 patients aged 1 to 21 with newly diagnosed acute lymphoblastic leukemia (ALL), calaspargase pegol demonstrated similar efficacy to the standard pegaspargase, achieving comparable rates of complete remission (99% for pegaspargase vs. 95% for calaspargase).

Calaspargase, administered every 3 weeks, showed a significantly higher serum asparaginase activity at day 25 compared to pegaspargase (88% vs. 17% with therapeutic levels), while both treatments had similar toxicity profiles and 5-year event-free survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001. Vrooman, LM., Blonquist, TM., Stevenson, KE., et al.[2021]

Calaspargase pegol (SC-PEG) provides a significantly longer half-life and greater systemic exposure of asparaginase activity compared to the standard pegaspargase (SS-PEG), with SC-PEG2500 showing a 2.5 times longer duration of activity.

Both SC-PEG formulations resulted in a longer period of asparagine depletion, lasting up to 18 days, while maintaining a comparable safety profile to SS-PEG in children with high-risk B-cell acute lymphoblastic leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Angiolillo, AL., Schore, RJ., Devidas, M., et al.[2021]

Calaspargase pegol-mknl (CALASP) was approved by the FDA for treating acute lymphoblastic leukemia (ALL) in pediatric and young adult patients, demonstrating its efficacy by maintaining steady-state nadir serum asparaginase activity (NSAA) above 0.1 U/mL in 99% of 124 patients studied.

CALASP showed a similar safety profile to pegaspargase (PEGASP) and did not significantly impair event-free survival, indicating it is a safe and effective option for ALL treatment when administered every 3 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Calaspargase Pegol-mknl For Treatment of Acute Lymphoblastic Leukemia in Children and Young Adults. Li, RJ., Jin, R., Liu, C., et al.[2020]

Calaspargase pegol-mknl (Asperlas) was approved by the FDA in December 2018 for the treatment of acute lymphoblastic leukemia (ALL) in children and young adults up to age 21, highlighting its importance in pediatric oncology.

The specific role of calaspargase within existing treatment protocols for ALL remains uncertain, indicating a need for further research to clarify its niche in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Space for Calaspargase? A New Asparaginase for Acute Lymphoblastic Leukemia. Lew, G.[2020]

In a study of 85 patients with adult acute lymphoblastic leukemia, those who achieved asparagine depletion after treatment with pegaspargase had significantly better overall survival (OS) and disease-free survival (DFS) compared to those who did not, indicating the importance of asparagine depletion in treatment outcomes.

The results suggest that effective asparagine depletion using pegaspargase is not only feasible but also linked to improved patient outcomes, supporting its use in intensive multiagent therapy for this type of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511. Wetzler, M., Sanford, BL., Kurtzberg, J., et al.[2021]

In a study involving 106 patients with acute lymphoblastic leukemia (ALL), generic pegylated asparaginase (P-Asp) was found to be effective, achieving higher mean trough levels compared to native asparaginase (N-Asp), indicating better drug availability.

Both P-Asp and N-Asp had similar rates of toxicity, but P-Asp showed a higher incidence of hospitalization for noninfectious causes during the induction phase, while both treatments had comparable 2-year event-free survival rates (84% for P-Asp and 80.7% for N-Asp).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Experience with generic pegylated L-asparaginase in children with acute lymphoblastic leukemia and monitoring of serum asparaginase activity. Vyas, C., Jain, S., Kapoor, G., et al.[2019]

In a study involving 551 children with newly diagnosed acute lymphoblastic leukaemia, intravenous PEG-asparaginase showed similar efficacy and toxicity compared to intramuscular native E. coli asparaginase, with no significant differences in asparaginase-related toxicities or disease-free survival rates.

Patients receiving intravenous PEG-asparaginase reported lower anxiety levels compared to those receiving intramuscular asparaginase, suggesting that PEG-asparaginase may improve the overall treatment experience for children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Place, AE., Stevenson, KE., Vrooman, LM., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Toxicity of Pegaspargase and Calaspargase Pegol in Childhood Acute Lymphoblastic Leukemia: Results of DFCI 11-001. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

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]

3. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Calaspargase Pegol-mknl For Treatment of Acute Lymphoblastic Leukemia in Children and Young Adults. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Space for Calaspargase? A New Asparaginase for Acute Lymphoblastic Leukemia. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Effective asparagine depletion with pegylated asparaginase results in improved outcomes in adult acute lymphoblastic leukemia: Cancer and Leukemia Group B Study 9511. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Pegasparaginase: where do we stand? [2019]

7. England pubmed.ncbi.nlm.nih.gov

Experience with generic pegylated L-asparaginase in children with acute lymphoblastic leukemia and monitoring of serum asparaginase activity. [2019]

8. England pubmed.ncbi.nlm.nih.gov

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]