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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the safety and tolerability of calaspargase pegol (CalPeg) when combined with chemotherapy for treating acute lymphoblastic leukemia (ALL). It targets individuals who have begun treatment for ALL with the Hyper-CVAD regimen and are ready for the next phase. Participants should have more than 10% leukemia cells in their blood or bone marrow at the start and should not have certain other health issues, such as heart problems or infections. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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.

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

Research shows that calaspargase pegol, the treatment under study, has been used to treat acute lymphoblastic leukemia (ALL) in children and young adults for some time. A previous study with 237 children tested calaspargase pegol alongside other cancer treatments. The results indicated that the drug is generally well-tolerated, though, like many cancer treatments, it can cause side effects. Common side effects include allergic reactions, liver issues, and pancreatic problems, similar to those seen with other ALL treatments.

Since the FDA has already approved calaspargase pegol for treating ALL, the treatment has a known safety profile. However, this study examines its use with a specific chemotherapy plan, so monitoring for new information about patient tolerance in this combination is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for Acute Lymphoblastic Leukemia (ALL), which often rely on traditional chemotherapy protocols, Calaspargase Pegol introduces a unique approach with its extended half-life. This means it stays active in the body longer, potentially allowing for fewer administrations while maintaining effectiveness. Additionally, Calaspargase Pegol is combined with Hyper-CVAD chemotherapy and, for patients with CD20+ ALL, the monoclonal antibody Rituximab, offering a more targeted therapy regimen. Researchers are optimistic about this treatment's ability to enhance outcomes by combining innovative drug action with existing therapies.

What evidence suggests that calaspargase pegol might be an effective treatment for acute lymphoblastic leukemia?

Studies have shown that calaspargase pegol effectively treats acute lymphoblastic leukemia (ALL), particularly in young patients. This medicine breaks down a nutrient that leukemia cells need to grow. In this trial, participants will receive calaspargase pegol with the Hyper-CVAD chemotherapy regimen. Research indicates that combining calaspargase pegol with other drugs can improve outcomes for people with ALL. It has been approved for use in children and young adults, underscoring its proven benefits for these age groups. This drug builds on years of experience with similar treatments, demonstrating its potential as a powerful component of leukemia therapy. ^{1 2 3 6 7}

Who Is on the Research Team?

Bijal Shah, MD

Principal Investigator

Moffitt Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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 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]

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