SC-PEG Asparaginase vs. Oncaspar for Acute Lymphoblastic Leukemia

Not currently recruiting at 10 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Dana-Farber Cancer Institute

Must not be taking: Investigational agents

Disqualifiers: HIV, Uncontrolled illness, Pregnancy, 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

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests two chemotherapy drugs, SC-PEG Asparaginase and Oncaspar, to determine which is more effective for treating acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma. The trial aims to compare the side effects and drug levels of SC-PEG, administered every three weeks, with Oncaspar, administered every two weeks. Researchers are also examining whether early antibiotic use can prevent serious infections and how vitamin D levels impact bone health during treatment. The trial is open to children and adolescents diagnosed with ALL or lymphoblastic lymphoma who have received minimal prior treatment. As a Phase 2 trial, this research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot participate if you have received certain treatments like chemotherapy or radiotherapy for previous cancer, or if you are taking other investigational drugs.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that SC-PEG Asparaginase and Oncaspar have been tested for safety in treating acute lymphoblastic leukemia (ALL). Oncaspar demonstrated strong safety results. In one study, 95.8% of patients remained alive five years after using Oncaspar as part of their treatment, indicating it is well-tolerated.

For SC-PEG Asparaginase, studies indicate it has a safety profile similar to other asparaginase treatments, like Oncaspar. Research suggests SC-PEG may remain active in the body longer than other forms, potentially working as effectively without causing additional side effects.

Both treatments can cause side effects, similar to those of other chemotherapy drugs used for ALL. Most side effects are manageable, and researchers continually seek ways to reduce them. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about SC-PEG Asparaginase and Oncaspar for treating Acute Lymphoblastic Leukemia because each offers unique benefits compared to standard options. SC-PEG Asparaginase is administered less frequently, with a dose every three weeks post-induction, which can be more convenient and potentially improve adherence compared to the bi-weekly schedule required for Oncaspar. Oncaspar is already a well-established treatment, but the study is exploring how its different dosing schedule impacts efficacy and side effects. Both treatments aim to enhance patient outcomes by targeting the leukemia cells more effectively with less frequent dosing, potentially reducing the burden of treatment.

What evidence suggests that this trial's treatments could be effective for acute lymphoblastic leukemia?

This trial will compare SC-PEG Asparaginase and Oncaspar for treating acute lymphoblastic leukemia (ALL). Research has shown that both SC-PEG and Oncaspar effectively treat ALL, but they differ in some aspects. SC-PEG, administered to participants in one arm of this trial, remains in the blood longer, maintaining necessary drug levels for an extended period. Specifically, studies indicate that 95% of patients treated with SC-PEG achieved complete remission. Oncaspar, given to participants in another arm, has a strong track record, with 84.9% of patients with ALL experiencing no major issues for five years. Both treatments reduce asparagine, a nutrient leukemia cells need to survive, which helps manage the disease. ^{1 2 3 6 7}

Who Is on the Research Team?

Andrew Place, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Are You a Good Fit for This Trial?

This trial is for children and adolescents with a confirmed diagnosis of ALL or lymphoblastic leukemia who haven't had previous treatments, except possibly short-term steroids, one dose of IT cytarabine, or urgent radiation. It's not for those with uncontrolled illnesses, pregnant/breastfeeding individuals, HIV-positive patients, anyone on other experimental drugs or extensive prior steroid use.

Inclusion Criteria

I have only had steroids, one dose of IT cytarabine, or emergency radiation for life-threatening masses.

I have been diagnosed with acute lymphoblastic leukemia.

Exclusion Criteria

I have had cancer before.

Receiving any other investigational agent

I do not have any uncontrolled illnesses.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Steroid Prophase

Initial phase of treatment typically given in the hospital to begin therapy

1 week

Remission Induction

Participants receive chemotherapy to induce remission, typically remaining in the hospital

4 weeks

Consolidation I

Further reduction of cancer cells in the body, with treatment given in the hospital

3 weeks

Central Nervous System (CNS) Phase

Treatment to prevent leukemia from returning in the brain, involving lumbar punctures and possibly radiation

3 weeks

Consolidation II

Chemotherapy given in cycles to further reduce cancer cells, typically as an outpatient

27 weeks

Continuation

Final phase to eliminate remaining cancer cells, with repeated cycles of chemotherapy

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Oncaspar
• SC-PEG Asparaginase

Trial Overview

The study compares SC-PEG Asparaginase to Oncaspar in treating pediatric acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma. Researchers want to see if SC-PEG's side effects are similar to Oncaspar when given every three weeks versus two and if it helps improve cure rates by adjusting treatment based on minimal residual disease levels.

How Is the Trial Designed?

Group I: SC-PEG (Arm A) Active Control 1 Intervention

Patients in this arm were randomized to receive IV Calaspargase Pegol (SC-PEG) 2500 IU/m2, administered as a single dose during induction and for 30 weeks post-induction. In the post-induction phases, IV SC-PEG was administered every 3 weeks (for a total of 10 post-induction doses). Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.

Group II: Oncaspar (Arm B) Active Control 1 Intervention

Patients in this arm were randomized to receive IV Oncaspar 2500 IU/m2, administered as a single dose during induction and for 30 weeks post-induction. In the post-induction phases, IV Oncaspar was administered every 2 weeks (for a total of 15 post-induction doses). Protocol therapy was comprised of 5 phases: Induction, Consolidation I, CNS, Consolidation II, and Continuation, and varied based off risk classification.

Who Is Running the Clinical Trial?

Dana-Farber Cancer Institute

Lead Sponsor

Trials

1,128

Recruited

382,000+

Shire

Industry Sponsor

Trials

457

Recruited

96,000+

Pierre S. Sayad

Shire

Chief Medical Officer

MD from Loma Linda University

Flemming Ornskov

Shire

Chief Executive Officer since 2013

PhD in Medicine from Aarhus University

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Pegaspargase is a crucial chemotherapy drug for treating acute lymphoblastic leukemia (ALL) in both children and adults, derived from E. coli, which requires careful management due to its specific toxicity profile.

The review highlights the importance of understanding and managing the common toxicities associated with Pegaspargase treatment to enhance safety, tolerability, and ultimately improve survival outcomes for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Prevention and management of pegaspargase associated-toxicities (excluding coagulation abnormalities). Recommendations of the French Society of Children and Adolescent Cancers (Leukemia committee)]. Poirée, M., Neumann, F., Thomas, C., et al.[2023]

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]

Pegaspargase (Oncaspar) was approved for first-line treatment of acute lymphoblastic leukemia (ALL) in children, showing similar efficacy to native L-asparaginase (Elspar) in depleting serum and cerebrospinal fluid asparagine levels during a clinical trial with 118 participants aged 1-9 years.

While both treatments had comparable event-free survival rates of around 80% at 3 years, pegaspargase was associated with serious toxicities such as anaphylaxis and thrombosis, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). Dinndorf, PA., Gootenberg, J., Cohen, MH., et al.[2022]

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]

Citations

1.

oncaspar.com

oncaspar.com/hcp/safety-efficacy

Proven Efficacy and Safety

84.9% of patients achieved 5-year EFS with ONCASPAR when administered for the full duration as part of a treatment regimen for ALL.1. DFCI 11-001 Study Design.

2.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9279693/

Current Use of Asparaginase in Acute Lymphoblastic ...

Pediatric Acute Lymphoblastic Leukemia (ALL) cure rates have improved exponentially over the past five decades with now over 90% of children ...

3.

ashpublications.org

ashpublications.org/blood/article/109/10/4164/22891/Effective-asparagine-depletion-with-pegylated

Effective asparagine depletion with pegylated asparaginase ...

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

4.

nature.com

nature.com/articles/s41375-024-02153-6

Increase in peg-asparaginase clearance as a predictor for ...

Efficacy and toxicity of pegaspargase and calaspargase pegol in childhood acute lymphoblastic leukemia: results of DFCI 11-001. J Clin Oncol.

5.

oncaspar.com

oncaspar.com/hcp/

HCP Home | ONCASPAR® (pegaspargase)

Efficacy and toxicity of pegaspargase and calaspargase pegol in childhood acute lymphoblastic leukemia: results of DFCI 11-001. J Clin Oncol. 2021;39(31): ...

6.

sciencedirect.com

sciencedirect.com/science/article/pii/S2468124524000135

Peg-asparaginase associated toxicities in children with ...

According to the CTCAE grading, approximately 70% of toxicities were categorized as Grade 3 and 4. Notably, 60% of the events occurred during the induction and ...

7.

clinicaltrials.gov

clinicaltrials.gov/study/NCT01574274

NCT01574274 | SC-PEG Asparaginase vs. Oncaspar in ...

Asparaginase is used to treat ALL and lymphoblastic lymphoma. The standard form of asparaginase, called Elspar, is given in the muscle once a week for 30 weeks.