Blinatumomab + Chemotherapy for Leukemia

Recruiting at 240 trial locations

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: National Cancer Institute (NCI)

Must not be taking: Cytotoxic chemotherapy, Hydroxyurea

Disqualifiers: Secondary ALL, CNS3 leukemia, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

6720 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase III trial studies how well blinatumomab works in combination with chemotherapy in treating patients with newly diagnosed, standard risk B-lymphoblastic leukemia or B-lymphoblastic lymphoma with or without Down syndrome. Monoclonal antibodies, such as blinatumomab, may induce changes in the body's immune system and may interfere with the ability of cancer cells to grow and spread. Chemotherapy drugs, such as vincristine, dexamethasone, prednisone, prednisolone, pegaspargase, methotrexate, cytarabine, mercaptopurine, doxorubicin, cyclophosphamide, and thioguanine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Leucovorin decreases the toxic effects of methotrexate. Giving monoclonal antibody therapy with chemotherapy may kill more cancer cells. Giving blinatumomab and combination chemotherapy may work better than combination chemotherapy alone in treating patients with B-ALL. This trial also assigns patients into different chemotherapy treatment regimens based on risk (the chance of cancer returning after treatment). Treating patients with chemotherapy based on risk may help doctors decide which patients can best benefit from which chemotherapy treatment regimens.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it mentions that patients should not have received prior cytotoxic chemotherapy for their current diagnosis. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Blinatumomab + Chemotherapy for Leukemia?

Research shows that asparaginase, a component of the treatment, is a critical part of leukemia therapy and has been effective in depleting asparagine, a nutrient leukemia cells need to grow. Pegaspargase, a form of asparaginase, is considered the standard due to its safety and effectiveness, and studies indicate that it achieves desired serum activity levels, contributing to the overall effectiveness of the treatment. ^{1 2 3 4 5}

What safety data exists for Blinatumomab + Chemotherapy for Leukemia?

The treatment involving Blinatumomab and various chemotherapy agents has shown some safety concerns. Common side effects include myelosuppression (reduced bone marrow activity), fever, vomiting, and liver toxicity. In some cases, severe reactions like hypersensitivity, pancreatitis, and central nervous system issues have been reported, but these effects are generally reversible. ^{3 6 7 8 9}

What makes the drug combination of Blinatumomab and Chemotherapy unique for treating leukemia?

This treatment combines Blinatumomab, a drug that helps the immune system target cancer cells, with a mix of chemotherapy drugs, including Pegaspargase, which has a longer-lasting effect and fewer allergic reactions compared to similar drugs. This combination aims to improve treatment effectiveness and reduce side effects for leukemia patients. ^{3 8 10 11 12}

Research Team

Sumit Gupta

Principal Investigator

Children's Oncology Group

Eligibility Criteria

This trial is for patients with newly diagnosed B-lymphoblastic leukemia/lymphoma, including those with Down syndrome. Participants must meet specific age and white blood cell count criteria and have not received prior cytotoxic chemotherapy (except certain steroids or intrathecal cytarabine). Exclusions include CNS3/testicular leukemia, secondary ALL from previous cancer treatment, Burkitt B-cell ALL, pregnancy, lactation.

Inclusion Criteria

I have been diagnosed with B-cell ALL or B-cell LLy, with or without Down syndrome.

I was diagnosed with B-ALL or B-LLy at an age that meets the trial's criteria, and I have Down syndrome.

All patients and/or their parents or legal guardians must sign a written informed consent.

Exclusion Criteria

I do not have specific conditions like T-Lymphoblastic Lymphoma, CNS disease, or am pregnant.

I am not currently on steroids or hydroxyurea.

I do not have CNS3, testicular leukemia, or AUL.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

Patients receive a combination of chemotherapy drugs including cytarabine, vincristine, dexamethasone, pegaspargase, and methotrexate. Treatment continues for 35 days.

5 weeks

Consolidation

Patients receive further chemotherapy to consolidate remission, including drugs like vincristine, mercaptopurine, and methotrexate. Treatment continues for 28-56 days depending on risk stratification.

4-8 weeks

Interim Maintenance

Patients receive vincristine and methotrexate with leucovorin rescue. Treatment continues for 56 days.

8 weeks

Delayed Intensification

Patients receive intensified chemotherapy including methotrexate, dexamethasone, vincristine, doxorubicin, pegaspargase, cyclophosphamide, thioguanine, and cytarabine. Treatment continues for 56 days.

8 weeks

Maintenance

Patients receive maintenance therapy with vincristine, dexamethasone, mercaptopurine, and methotrexate. Treatment repeats every 84 days until a total duration of therapy of 2 years from start of Interim Maintenance I is reached.

2 years

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 4 weeks until blood count recovery, then every 3 months for the first 2 years, every 4-6 months for the 3rd year, and every 6-12 months for the 4th and 5th years.

5 years

Treatment Details

Interventions

• Asparaginase Erwinia chrysanthemi
• Blinatumomab
• Cyclophosphamide
• Cytarabine
• Dexamethasone
• Doxorubicin Hydrochloride
• Leucovorin Calcium
• Mercaptopurine
• Methotrexate
• Pegaspargase
• Prednisolone
• Prednisone
• Radiation Therapy
• Vincristine Sulfate

Trial Overview The study tests blinatumomab combined with chemotherapy drugs like vincristine and methotrexate in treating standard risk B-ALL/B-LLy. It aims to see if this monoclonal antibody plus chemo improves outcomes compared to chemo alone. Patients are grouped by cancer recurrence risk to tailor the treatment regimen.

Participant Groups

Group I: NCI SR or HR DS B-ALL Experimental Treatment 12 Interventions

See detailed description.

Group II: DS B-ALL Experimental Treatment 13 Interventions

See detailed description.

Group III: B-LLy Experimental Treatment 14 Interventions

See detailed description.

Group IV: Arm D (SR-High experimental) Experimental Treatment 15 Interventions

Arm D See detailed description.

Group V: Arm B (SR-Avg experimental) Experimental Treatment 13 Interventions

Arm B: See detailed description.

Group VI: Arm C (SR-High Control) Active Control 14 Interventions

Arm C: See detailed description.

Group VII: Arm A (SR-Avg control) Active Control 13 Interventions

Arm A: See detailed description.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

References

1. China pubmed.ncbi.nlm.nih.gov

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

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

Pharmacokinetics, pharmacodynamics, efficacy, and safety of a new recombinant asparaginase preparation in children with previously untreated acute lymphoblastic leukemia: a randomized phase 2 clinical trial. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Toxicity of sequential high-dose ARA-C asparaginase treatment in childhood poor risk leukemia. [2019]

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

Clinical pharmacology of asparaginases in the United States: asparaginase population pharmacokinetic and pharmacodynamic (PK-PD) models (NONMEM) in adult and pediatric ALL patients. [2011]

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

Universal premedication and therapeutic drug monitoring for asparaginase-based therapy prevents infusion-associated acute adverse events and drug substitutions. [2021]

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

Toxicity of a Modified PEG-Asparaginase-Based SMILE Regimen Is Comparable to L-Asparaginase-Based SMILE in a Non-Asian Population. [2023]

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

Intensified PEG-L-asparaginase and antimetabolite-based therapy for treatment of higher risk precursor-B acute lymphoblastic leukemia: a report from the Children's Oncology Group. [2018]

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

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

9. England pubmed.ncbi.nlm.nih.gov

The use of Erwinia asparaginase for adult patients with acute lymphoblastic leukemia after pegaspargase intolerance. [2020]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Pegaspargase: A Review in Acute Lymphoblastic Leukaemia. [2023]

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

The effect of asparaginase therapy on methotrexate toxicity and efficacy in children with acute lymphoblastic leukemia. [2020]

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

Antimetabolite-based therapy in childhood T-cell acute lymphoblastic leukemia: a report of POG study 9296. [2009]