Drug Combination for Childhood Leukemia

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: CYP3A4 inducers, CYP3A inhibitors

Disqualifiers: Recent HCT, CNS leukemia, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 3

Duration: 14 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates a new drug combination to determine its safety and effectiveness in treating childhood leukemia, specifically for patients whose B-cell acute lymphoblastic leukemia (ALL) has relapsed or not responded to other treatments. The trial combines three drugs: asparaginase Erwinia chrysanthemi (a protein that may stop cancer growth), venetoclax (a drug that blocks a protein needed for cancer cells to survive), and blinatumomab (which helps the immune system target cancer cells). Eligible participants include those with CD19 positive B-cell ALL that has relapsed or is refractory and have more than 5% blasts (cancer cells) in their bone marrow. 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 combination therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking strong and moderate CYP3A4 inducers and strong CYP3A inhibitors at least 7 days before starting the study. You also need to avoid certain foods and supplements like grapefruit and St. John's wort 3 days before and during the study. Other medications may need to be discussed with the study team.

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

Previous studies have shown that blinatumomab is safe for children with B-cell acute lymphoblastic leukemia (ALL). Serious side effects were rare, and most children tolerated it well. Research on recombinant Erwinia asparaginase, used when patients cannot tolerate another form of asparaginase, has demonstrated safety similar to other treatments, with no new safety issues identified.

For venetoclax, studies suggest it is well-tolerated in children with other types of leukemia, with a safety profile similar to that in adults. Common side effects were reported, but no new serious concerns emerged.

Since this trial is in its early phase, the main goal is to assess the safety of these drugs when used together. At this stage, the treatment undergoes careful safety evaluation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about this treatment for childhood leukemia because it combines three drugs with unique mechanisms of action. Blinatumomab is a bispecific T-cell engager that directs the body's immune system to target and destroy leukemia cells. Recombinant Erwinia Asparaginase breaks down asparagine, a nutrient leukemia cells need to survive, effectively starving them. Venetoclax inhibits the BCL-2 protein, which helps cancer cells evade death, thus promoting their destruction. This multi-pronged approach targets leukemia from different angles, potentially offering a more powerful and effective treatment than the current standard options.

What evidence suggests that this trial's treatments could be effective for relapsed or refractory B-cell acute lymphoblastic leukemia?

Research has shown that blinatumomab yields promising results in treating children with B-cell acute lymphoblastic leukemia (ALL). In one study, about 39% of patients achieved complete remission, with no cancer cells detected in their blood. Another study found that 96% of children treated with blinatumomab remained leukemia-free for three years.

Recombinant Erwinia asparaginase also proves effective for ALL patients, particularly those who cannot tolerate other asparaginase treatments. It helps maintain necessary treatment levels in the body to inhibit cancer cell growth.

Venetoclax, a BCL-2 inhibitor, has demonstrated high success rates in treating pediatric leukemia. Trials showed it was well-tolerated and led to deep remission, with no detectable cancer cells, in many patients. This trial tests the combination of blinatumomab, recombinant Erwinia asparaginase, and venetoclax for its potential to effectively treat ALL that has returned or is unresponsive to other treatments. ^{1 4 6 7 8}

Who Is on the Research Team?

Amandeep Salhotra

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for patients with CD19 positive B-cell acute lymphoblastic leukemia (ALL) that has relapsed or is refractory. Specific eligibility criteria are not provided, but typically include factors like age, health status, and previous treatments.

Inclusion Criteria

Creatinine clearance of ≥ 60 mL/min per 24 hour urine test or the Cockcroft-Gault formula

Aspartate aminotransferase (AST) ≤ 2.5 x ULN (Unless it is related to underlying leukemia, then AST ≤ 5 x ULN)

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

Exclusion Criteria

History of alcohol overuse

Known hypersensitivity to blinatumomab/ recombinant Erwinia asparaginase or to any component of the product formulation

I can follow all the study's required procedures.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Pre-Phase Treatment/Bridge Therapy

Optional administration of cyclophosphamide, vincristine, and prednisone to prepare patients for main treatment

3 days

1 visit (in-person)

Treatment

Patients receive asparaginase Erwinia chrysanthemi, venetoclax, and blinatumomab over two cycles

14 weeks

Multiple visits (in-person) for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Blinatumomab
• Recombinant Erwinia Asparaginase
• Venetoclax

Trial Overview The trial tests recombinant Erwinia asparaginase combined with venetoclax and blinatumomab in treating relapsed/refractory ALL. It evaluates the safety/side effects of this combination and its effectiveness against cancer cells.

How Is the Trial Designed?

Group I: Treatment (asparaginase, venetoclax, blinatumomab) Experimental Treatment 11 Interventions

PRE-PHASE TREATMENT/BRIDGE THERAPY: Starting days -7 to -5, patients may optionally receive cyclophosphamide and vincristine on day 1 and prednisone on days 1-5. TREATMENT: Patients receive asparaginase Erwinia chrysanthemi IM on days 1,3, 5, 7, 9, 11, and 13, venetoclax PO QD on days 1-14 or QOD on days 1, 3, 5, 7, 9, 11, and 13 of each cycle and blinatumomab CIV on days 8-35 of cycle 1 and on days 1-28 of cycle 2. Cycles repeat every 49 days for cycle 1 and 42 days for cycle 2 for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo ECHO and MUGA at screening and bone marrow aspiration and biopsy, blood sample collection, and lumbar puncture throughout the study.

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+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12325004/

Blinatumomab in pediatric B-acute lymphoblastic leukemia A phase III multicenter randomized clinical trial reported significantly improved outcomes with blinatumomab, including 2-year overall survival ...

2. ashpublications.org ashpublications.org/bloodadvances/article/9/15/3946/537699/Blinatumomab-use-in-pediatric-B-ALL-where-are-we

Blinatumomab use in pediatric B-ALL: where are we now? Among 70 patients who received the recommended dosage, 27 (39%) achieved a complete remission (CR; defined as no circulating blasts or ...

3. nejm.org nejm.org/doi/abs/10.1056/NEJMoa2411680

Blinatumomab in Standard-Risk B-Cell Acute ... At a median follow-up of 2.5 years, the estimated 3-year disease-free survival (±SE) was 96.0±1.2% with blinatumomab and chemotherapy and 87.9± ...

4. healthtree.org healthtree.org/all/community/articles/ash-24-blina-pediatric-all-improves-survival

Blinatumomab: New Standard in Children's Leukemia After three years, 96% of children who received blinatumomab remained leukemia-free, compared to 87.9% with standard treatment alone. The ...

5. cureus.com cureus.com/articles/379864-efficacy-of-blinatumomab-in-pediatric-acute-lymphoblastic-leukemia-a-systematic-review-and-meta-analysis-of-randomized-controlled-trials.pdf

Efficacy of Blinatumomab in Pediatric Acute Lymphoblastic ... Among 70 treated patients, 27 achieved CR within the first two cycles, and 14 reached complete MRD remission [14].

6. frontiersin.org frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.929122/full

The safety of blinatumomab in pediatric patients with acute ... In our meta-analysis, blinatumomab showed a good safety profile with a lower risk of serious adverse events, grade ≥ 3 adverse events, and ...

7. ashpublications.org ashpublications.org/thehematologist/article/doi/10.1182/hem.V22.1.2025210/535045/Blin-ing-Is-Winning-for-Children-With-B-Cell-Acute

ing Is Winning for Children With B-Cell Acute Lymphoblastic ... Blinatumomab was previously reported to be both safe and effective in children and adolescents/young adults with R/R B-ALL.

8. blincytohcp.com blincytohcp.com/clinical-data/pediatric-aya/cog-aall-1731-study

Pediatric & AYA COG AALL1731 Study Explore data from the COG AALL1731 study evaluating BLINCYTO® (blinatumomab) in pediatric and AYA patients with B-cell ALL as part of frontline therapy.