Calaspargase Pegol for Acute Lymphoblastic Leukemia

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Calaspargase pegol, a type of enzyme therapy, for adults with Philadelphia-negative Acute Lymphoblastic Leukemia (ALL). The main goal is to determine the optimal dosage and ensure the treatment's safety and efficacy. It is suitable for individuals recently diagnosed with this type of leukemia who have not started other treatments, except for short-term use of certain medications. As a Phase 2, Phase 3 trial, this study evaluates the treatment's effectiveness in a smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking therapy.

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.

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

Research has shown that calaspargase pegol is safe for treating acute lymphoblastic leukemia (ALL), particularly in children. Trials involving 208 children with ALL or lymphoblastic lymphoma found the treatment to be well-tolerated, with manageable side effects. The FDA has also approved calaspargase pegol for use in children, indicating a level of safety confidence. Although this study focuses on adults, existing data from its use in children offers positive insights into its safety. Participants should discuss any concerns with their healthcare provider before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Calaspargase pegol is unique because it offers a longer-lasting effect compared to traditional asparaginase treatments for acute lymphoblastic leukemia (ALL). Most treatments for ALL use asparaginase, which breaks down quickly in the body, requiring frequent dosing. Calaspargase pegol, on the other hand, is a pegylated form, which means it stays active in the body longer, potentially reducing the number of doses a patient needs. Researchers are excited about this treatment because it could lead to fewer hospital visits and improved convenience for patients, while maintaining or even enhancing the effectiveness of leukemia treatment.

What evidence suggests that Calaspargase pegol might be an effective treatment for Acute Lymphoblastic Leukemia?

Research has shown that calaspargase pegol, the treatment under study in this trial, effectively treats acute lymphoblastic leukemia (ALL). Studies have found that it extends the activity of asparaginase in the body, which is crucial for combating leukemia cells. This activity reduces asparagine, a nutrient necessary for leukemia cell survival. Calaspargase pegol is considered essential for treating ALL and lymphoblastic lymphoma. These findings suggest that calaspargase pegol could be a promising option for patients with Philadelphia-negative ALL. ^{1 2 6 7 8}

Who Is on the Research Team?

Daniel DeAngelo, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute, Boston, MA

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 (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 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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4239306/

Results From Children's Oncology Group Study AALL07P4 Asparaginase is a critical agent used to treat acute lymphoblastic leukemia (ALL). Pegaspargase (SS-PEG), a pegylated form of Escherichia coli L-asparaginase ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT00671034

Study Details | NCT00671034 | Calaspargase Pegol or ... This randomized clinical trial is studying giving calaspargase pegol together with combination chemotherapy to see how well it works compared with giving ...

3. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2014.55.5763

Results From Children's Oncology Group Study AALL07P4 SC-PEG2500 achieves a significantly longer period of asparaginase activity above defined thresholds and asparagine depletion compared with SS-PEG2500.

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/25348002/

results from Children's Oncology Group Study AALL07P4 SC-PEG2500 achieves a significantly longer period of asparaginase activity above defined thresholds and asparagine depletion compared with SS-PEG2500.

5. aetna.com aetna.com/cpb/medical/data/900_999/0957.html

Calaspargase pegol (Asparlas) - Medical Clinical Policy ... Aetna considers calaspargase pegol - mknl (Asparlas) medically necessary for the treatment of acute lymphoblastic leukemia or lymphoblastic lymphoma.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2021/761102s008lbl.pdf

ASPARLAS (calaspargase pegol - mknl) Label The trials included 208 children with ALL or lymphoblastic lymphoma treated with. ASPARLAS; there were 19 infants (1 month to < 2 years old), 128 children (2 ...

7. ascopubs.org ascopubs.org/doi/10.1200/jco.2012.30.15_suppl.9543

Results from Children's Oncology Group (COG) study ... Plasma asparaginase activity and asparagine depletion in patients with acute lymphoblastic leukemia (ALL) treated with pegaspargase (SS-PEG E.

8. aacrjournals.org aacrjournals.org/clincancerres/article/26/2/328/82761/FDA-Approval-Summary-Calaspargase-Pegol-mknl-For

FDA Approval Summary: Calaspargase Pegol-mknl For ... The incorporation of asparaginase agents as a component of therapy was shown to add a 15% to 20% survival benefit to children with ALL (1), and adherence to the ...