CalPeg + Chemotherapy for Acute Lymphoblastic Leukemia

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: H. Lee Moffitt Cancer Center and Research Institute

Must be taking: Multi-agent chemotherapy

Disqualifiers: CNS leukemia, Down Syndrome, active infection, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

20 Participants Needed

Trial Summary

What is the purpose of this trial?

The purpose of the study is to evaluate the safety and tolerability of the study drug, calaspargase pegol, when given with multi-agent chemotherapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

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 successful treatment of Acute Lymphoblastic Leukemia. It has a similar safety profile to the standard treatment and does not negatively impact survival rates. ^{1 2 3 4 5}

Is Calaspargase Pegol safe for use in humans?

Calaspargase Pegol, used in treating acute lymphoblastic leukemia (ALL) in children and young adults, has a similar safety profile to the standard treatment, pegaspargase, when used in combination with chemotherapy. It was approved by the FDA in 2018, indicating it met safety standards for its intended use. ^{1 2 3 4 6}

What makes the drug Calaspargase Pegol unique for treating acute lymphoblastic leukemia?

Calaspargase Pegol is unique because it has a longer half-life than the standard treatment, pegaspargase, allowing it to be administered every 3 weeks instead of every 2 weeks, while maintaining similar safety and effectiveness. ^{1 2 3 4 7}

Research Team

Bijal Shah, MD

Principal Investigator

Moffitt Cancer Center

Eligibility Criteria

This trial is for adults with newly diagnosed acute lymphoblastic leukemia (ALL) who are in good physical condition (ECOG 0-1), have a functioning heart, liver, and kidneys, and can follow the study schedule. Women must use effective non-hormonal birth control or abstain from sex; men also need to use contraception. Excluded are those with other cancers, certain infections like HIV/Hepatitis B/C, recent major surgery or radiation therapy, CNS leukemia symptoms, severe health conditions affecting participation safety.

Inclusion Criteria

I am fully active or can carry out light work.

Be willing and able to provide written informed consent/assent for the trial

Able to adhere to the study visit schedule and other protocol requirements

Exclusion Criteria

I have been diagnosed with L3 type Burkitt's lymphoma.

I have active leukemia in my brain or spinal cord.

I received initial cancer treatment that was not Hyper-CVAD 1A.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive calaspargase pegol with Hyper-CVAD, mini-CVD, and late intensification, starting with Cycle 1B. Responding patients will have dose reduction for Cycles 2B-4B. CD20+ ALL patients receive Rituximab once per cycle.

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment, with MRD assessments every 3 months in the first year and every 6 months in the subsequent 2 years.

3 years

Long-term follow-up

Participants are monitored for progression-free survival and overall survival.

42 months

Treatment Details

Interventions

• Calaspargase Pegol

Trial Overview The trial tests calaspargase pegol's safety when combined with Hyper CVAD chemotherapy and rituximab in treating ALL. Participants will receive this combination treatment to see how well they tolerate it compared to standard treatments alone.

Participant Groups

Group I: Hyper-CVAD + Calaspargase pegol Treatment Experimental Treatment 3 Interventions

Participants will receive calaspargase pegol administered over 1 hour with each cycle of Hyper-CVAD, mini-CVD, and late intensification, beginning with Cycle 1B. Responding patients will have dose reduction of HyperCVAD for Cycles 2B-4B. Participants with CD20+ ALL will also be given Rituximab once per cycle.

Calaspargase Pegol is already approved in United States, Canada 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

Approved in Canada as Asparlas for:

• Acute lymphoblastic leukemia (ALL)

Who Is Running the Clinical Trial?

H. Lee Moffitt Cancer Center and Research Institute

Lead Sponsor

Trials

576

Recruited

145,000+

Servier

Industry Sponsor

Trials

55

Recruited

45,600+

Findings from Research

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 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]

In a study of 135 children with newly diagnosed acute lymphoblastic leukemia (ALL), the PEG-Asp containing VDPAP regimen showed similar efficacy to the L-asparaginase containing VDLP regimen, with complete remission rates of 84.6% and 89.4%, respectively.

PEG-Asp demonstrated a longer half-life of about 7 days, providing a more prolonged therapeutic effect, while both regimens had comparable rates of adverse effects, primarily allergic reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Comparison of polyethylene glycol conjugated asparaginase and L-asparaginase for treatment of childhood acute lymphoblastic leukemia]. [2018]

Capping the dose of pegaspargase at 3750 units did not significantly reduce the incidence of serious adverse events in adults compared to higher doses, indicating that this practice may not be necessary for safety.

The overall incidence of serious toxicities related to pegaspargase was low, suggesting that with careful monitoring and preventive measures, pegaspargase can be safely used in older patients with acute lymphoblastic leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of pegaspargase dose capping on incidence of pegaspargase-related adverse events in adults. Tiao, E., Bernhardi, CL., Trovato, JA., et al.[2023]

In a study of 268 children with newly diagnosed acute lymphoblastic leukemia (ALL), polyethylene glycol conjugated asparaginase (peg-asp) demonstrated similar efficacy to native Escherichia coli asparaginase during induction treatment, indicating it can be a viable alternative.

The results suggest that pegaspargase can be considered not only for patients with allergies to native asparaginase but also as a first-line treatment option for newly diagnosed patients, as it achieved comparable bone marrow response rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Efficacy observation of polyethylene glycol conjugated asparaginase for induction treatment of children with newly diagnosed acute lymphoblastic leukemia]. Liu, F., Wan, Y., Chang, L., et al.[2018]

References

1. 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]

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

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

3. 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]

4. 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]

5. China pubmed.ncbi.nlm.nih.gov

[Comparison of polyethylene glycol conjugated asparaginase and L-asparaginase for treatment of childhood acute lymphoblastic leukemia]. [2018]

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

Impact of pegaspargase dose capping on incidence of pegaspargase-related adverse events in adults. [2023]

7. China pubmed.ncbi.nlm.nih.gov

[Efficacy observation of polyethylene glycol conjugated asparaginase for induction treatment of children with newly diagnosed acute lymphoblastic leukemia]. [2018]