Asparaginase Erwinia Chrysanthemi + Chemotherapy for Blood Cancer

Recruiting at 6 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: City of Hope Medical Center

Must not be taking: Asparaginase, Live vaccines

Disqualifiers: Ph+, CNS involvement, cardiovascular, 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: 1

53 Participants Needed

Trial Summary

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain treatments like live vaccines are not allowed during the study, and some medications may need to be adjusted. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Asparaginase Erwinia chrysanthemi for blood cancer?

Asparaginase Erwinia chrysanthemi is used to treat acute lymphoblastic leukemia (a type of blood cancer) and has shown similar effectiveness to other asparaginase drugs with potentially lower toxicity. It is particularly noted for having fewer coagulation issues compared to its counterpart derived from E. coli. ^{1 2 3 4 5}

Is Asparaginase Erwinia Chrysanthemi safe for use in humans?

Asparaginase Erwinia Chrysanthemi is generally considered safe for use in humans, with fewer side effects compared to its counterpart derived from Escherichia coli. However, it can still cause side effects like allergic reactions, pancreatitis (inflammation of the pancreas), and blood clotting issues. ^{1 2 5 6 7}

How is the drug Asparaginase Erwinia chrysanthemi different from other treatments for blood cancer?

Asparaginase Erwinia chrysanthemi is unique because it is used specifically for patients who have allergic reactions to the more common E. coli-derived asparaginase. It has a different source and shorter duration in the body, making it a suitable alternative for those who cannot tolerate the standard treatment. ^{5 6 8 9 10}

What is the purpose of this trial?

This phase II trial tests the safety, side effects, and effectiveness of asparaginase Erwinia chrysanthemi during induction chemotherapy followed by consolidation chemotherapy in treating high-risk adults with newly diagnosed acute lymphoblastic leukemia or lymphoblastic lymphoma. Asparaginase Erwinia chrysanthemi, a type of protein synthesis inhibitor, is a drug that is made up of the enzyme asparaginase, which comes from the bacterium Erwinia chrysanthemi, and is used with other drugs in people who cannot take asparaginase that comes from the bacterium E. coli. Asparaginase Erwinia chrysanthemi breaks down the amino acid asparagine and may stop the growth of cancer cells that need asparagine to grow. It may also kill cancer cells. Induction therapy, consisting of cytarabine, dexamethasone, vincristine, daunorubicin, methotrexate, and rituximab, is the first choice of treatment. Consolidation therapy, consisting of cyclophosphamide, cytarabine, vincristine, mercaptopurine, methotrexate and rituximab, is given after initial therapy to kill any remaining cancer cells. Vincristine is in a class of medications called vinca alkaloids. It works by stopping cancer cells from growing and dividing and may kill them. Methotrexate is in a class of medications called antimetabolites. It is also a type of antifolate. Methotrexate stops cells from using folic acid to make deoxyribonucleic acid (DNA) and may kill cancer cells. Rituximab is a monoclonal antibody. It binds to a protein called CD20, which is found on B cells (a type of white blood cell) and some types of cancer cells. This may help the immune system kill cancer cells. Cyclophosphamide is in a class of medications called alkylating agents. It works by damaging the cell's DNA and may kill cancer cells. It may also lower the body's immune response. Cytarabine and mercaptopurine stop cells from making DNA and may kill cancer cells. They are a type of antimetabolite. Daunorubicin blocks a certain enzyme needed for cell division and DNA repair and may kill cancer cells. It is a type of anthracycline antibiotic and a type of topoisomerase inhibitor. Dexamethasone is in a class of medications called corticosteroids. It is used to reduce inflammation and lower the body's immune response to help lessen the side effects of chemotherapy drugs. Giving asparaginase Erwinia chrysanthemi with induction chemotherapy followed by consolidation chemotherapy may be safe, tolerable, and/or effective in treating high-risk adults with newly diagnosed acute lymphoblastic leukemia or lymphoblastic lymphoma.

Research Team

Ibrahim Aldoss

Principal Investigator

City of Hope Medical Center

Eligibility Criteria

Adults newly diagnosed with high-risk acute lymphoblastic leukemia or lymphoblastic lymphoma are eligible for this trial. The study is designed for those who can't take the E. coli-derived asparaginase and need an alternative treatment.

Inclusion Criteria

Prothrombin (PT) ≤ 1.5 ULN (within 14 days prior to day 1 of protocol therapy)

My heart's pumping ability is normal.

Documented informed consent of the participant and/or legally authorized representative

Exclusion Criteria

I haven't had a heart attack or unstable angina in the last 6 months.

I have another active cancer besides the one being treated.

I am not pregnant or breastfeeding.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive induction therapy with cytarabine, dexamethasone, vincristine, daunorubicin, asparaginase Erwinia chrysanthemi, and methotrexate. CD20 positive patients also receive rituximab.

4 weeks

Weekly visits for drug administration

Extended Induction

Patients with M2 marrow receive extended induction therapy with dexamethasone, vincristine, daunorubicin, and asparaginase Erwinia chrysanthemi.

2 weeks

Consolidation

Patients receive consolidation therapy with cyclophosphamide, cytarabine, mercaptopurine, vincristine, methotrexate, and rituximab for CD20 positive patients.

8 weeks

Bi-weekly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

Treatment Details

Interventions

• Asparaginase Erwinia chrysanthemi
• Cyclophosphamide
• Cytarabine
• Daunorubicin Hydrochloride
• Dexamethasone
• Mercaptopurine
• Methotrexate
• Rituximab
• Vincristine Sulfate

Trial Overview The trial tests asparaginase Erwinia chrysanthemi combined with induction chemotherapy (cytarabine, dexamethasone, vincristine, daunorubicin, methotrexate, rituximab), followed by consolidation therapy to kill any remaining cancer cells.

Participant Groups

Group I: Treatment (asparaginase Erwinia chrysanthemi) Experimental Treatment 16 Interventions

See Detailed Description

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

References

1. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Mechanisms of development of side effects and drug resistance to asparaginase and ways to overcome them]. [2022]

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

Asparaginase revisited. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Unexpected mortality from the use of E. coli L-asparaginase during remission induction therapy for childhood acute lymphoblastic leukemia: a report from the Taiwan Pediatric Oncology Group. [2019]

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

Plasma asparaginase activity, asparagine concentration, and toxicity after administration of Erwinia asparaginase in children and young adults with acute lymphoblastic leukemia: Phase I/II clinical trial in Japan. [2017]

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

Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of Cancer-Children's Leukemia Group phase 3 trial. [2021]

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

Safety profile of asparaginase Erwinia chrysanthemi in a large compassionate-use trial. [2020]

7. England pubmed.ncbi.nlm.nih.gov

A comparison of hypersensitivity reactions between intravenous and intramuscular applications of native E. coli asparaginase in children with acute lymphoblastic leukemia. [2023]

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

Activity and Toxicity of Intravenous Erwinia Asparaginase Following Allergy to E. coli-Derived Asparaginase in Children and Adolescents With Acute Lymphoblastic Leukemia. [2020]

9. Italy pubmed.ncbi.nlm.nih.gov

Back to the future: the amazing journey of the therapeutic anti-leukemia enzyme asparaginase Erwinia chrysanthemi. [2023]

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

Asparaginase Erwinia chrysanthemi as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia who have developed hypersensitivity to E. coli-derived asparaginase. [2020]