SC-PEG Asparaginase vs. Oncaspar for Acute Lymphoblastic Leukemia

Recruiting at 9 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

240 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is being conducted to learn about the effects of SC-PEG, which is a new form of a chemotherapy drug called asparaginase. 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. There are other forms of asparaginase. The investigators will be studying two of these: Oncaspar and Calaspargase Pegol (SC-PEG). The investigators have previously studied giving Oncaspar in the vein (instead of the muscle) every 2 weeks in patients with ALL, and have shown that this dosing did not lead to any more side effects than Elspar given weekly in the muscle. The study drug, SC-PEG, is very similar but not identical to Oncaspar. SC-PEG has been given in the vein to children and adolescents with ALL as part of other research studies, and it appears to last longer in the blood after a dose than Oncaspar. It has not yet been approved by the FDA. The goal of this research study is to learn whether the side effects and drug levels of SC-PEG given in the vein every 3 weeks are similar to Oncaspar given into the vein about every 2 weeks. The study will also help to determine whether changing treatment for children and adolescents with ALL with high levels of minimal residual disease may improve cure rates. Measuring minimal disease (MRD) is a laboratory test that finds low levels of leukemia cells that the investigators cannot see under the microscope. In the past, it has been shown that children and adolescents with ALL with high levels of MRD after one month of treatment are less likely to be cured than those with low levels of MRD. Therefore, on the study, the bone marrow and blood at the end of the first month of treatment will be measured in participants with leukemia, and changes in therapy will be implemented based on this measurement. It is not known for sure that changing treatment will improve cure rates. MRD levels can only be measured if the marrow is filled with cancer cells at the time of diagnosis. Therefore, MRD studies will only be done in children and adolescents with ALL and not in those with lymphoblastic lymphoma. Another part of the study is to determine whether giving antibiotics during the first month of treatment even to participants without fever will prevent serious infections in the blood and other parts of the body. About 25% of children and adolescents with ALL and lymphoblastic lymphoma who receive standard treatment develop a serious blood infection from a bacteria during the first month of treatment. Typically, antibiotics (medicines that fight bacteria) are given by vein only after a child with leukemia or lymphoma develops a fever or have other signs of infection. In this study, antibiotics will be given by mouth or in the vein to all participants during the first month of treatment, whether or not they develop fever. Another goal of the study to learn how vitamin D levels relate to bone problems (such as broken bones or fractures) that children and adolescents with ALL and lymphoblastic lymphoma experience while on treatment. Some of the chemotherapy drugs used to treat ALL and lymphoblastic lymphoma can make bones weaker, which make fractures more likely. Vitamin D is a natural substance from food and sunlight that can help keep bones strong. The investigators will study how often participants have low levels of vitamin D while receiving chemotherapy, and, for those with low levels, whether giving vitamin D supplements will increase those levels. Another focus of the study is to learn more about the biology of ALL and lymphoblastic lymphoma by doing research on blood, bone and spinal fluid bone marrow samples. The goal of this research is to improve treatment for children with leukemia in the future.

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.

What data supports the effectiveness of the drug Oncaspar for treating acute lymphoblastic leukemia?

Research shows that pegylated asparaginase (PEG-ASP), the active component in Oncaspar, is effective in treating acute lymphoblastic leukemia (ALL) in both children and adults. It has a longer-lasting effect and causes fewer allergic reactions compared to older versions of the drug, making it a preferred choice in multi-drug chemotherapy regimens for ALL. ^{1 2 3 4 5}

Is SC-PEG Asparaginase (Oncaspar) safe for humans?

SC-PEG Asparaginase (Oncaspar) has been used in treating acute lymphoblastic leukemia, but it can cause serious side effects like allergic reactions, pancreatitis (inflammation of the pancreas), and blood clotting issues. Safety concerns are higher in older adults and those with certain genetic conditions, and the method of administration (IV vs. IM) can affect the severity of allergic reactions. ^{6 7 8 9 10}

How does the drug SC-PEG Asparaginase differ from other treatments for acute lymphoblastic leukemia?

SC-PEG Asparaginase is a modified form of the enzyme asparaginase, which is used to treat acute lymphoblastic leukemia (ALL). It has a unique chemical structure that makes it more stable and potentially less toxic than other forms, allowing for longer-lasting effects in the body. This can be particularly beneficial for patients who have allergic reactions to other asparaginase products. ^{1 2 3 11 12}

Research Team

Andrew Place, MD, PhD

Principal Investigator

Dana-Farber Cancer Institute

Eligibility Criteria

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.

I do not have any uncontrolled illnesses.

Receiving any other investigational agent

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

References

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

Prolonged first-line PEG-asparaginase treatment in pediatric acute lymphoblastic leukemia in the NOPHO ALL2008 protocol-Pharmacokinetics and antibody formation. [2018]

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

Intermittent Versus Continuous PEG-Asparaginase to Reduce Asparaginase-Associated Toxicities: A NOPHO ALL2008 Randomized Study. [2020]

3. Italy pubmed.ncbi.nlm.nih.gov

A pharmacological study on pegylated asparaginase used in front-line treatment of children with acute lymphoblastic leukemia. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Pegasparaginase: where do we stand? [2019]

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

[Influence of L-asaraginase and Pegaspargase on Coagulation Function of Adult Patients with Acute Lymphoblastic Leukemia and Analysis of Related Factors]. [2018]

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

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

7. France 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)]. [2023]

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

FDA drug approval summary: pegaspargase (oncaspar) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). [2022]

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

Allergic reactions associated with pegaspargase in adults. [2019]

10. England pubmed.ncbi.nlm.nih.gov

Pegylated-asparaginase during induction therapy for adult acute lymphoblastic leukaemia: toxicity data from the UKALL14 trial. [2021]

11. Poland pubmed.ncbi.nlm.nih.gov

[New possibilities of treatment with PEG-L-asparaginase in patients with acute lymphoblastic leukemia sensitized to l-asparaginase E.coli and erwinase]. [2018]

12. 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]