Tagraxofusp + Chemotherapy for Acute Lymphoblastic Leukemia

Overseen By Nicholas Short

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Investigational agents

Disqualifiers: CNS leukemia, Philadelphia chromosome-positive ALL, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for certain blood cancers, specifically acute lymphoblastic leukemia and lymphoblastic lymphoma, that have returned or don't respond to treatment. It combines tagraxofusp, a targeted therapy that kills specific cancer cells, with chemotherapy to determine if this approach can better control the disease. The trial seeks participants with CD123-positive acute lymphoblastic leukemia or lymphoblastic lymphoma that has relapsed or is refractory. 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 therapy.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have taken any investigational antileukemic or chemotherapy agents in the last 7 days before joining the study, unless you have fully recovered from side effects or have life-threatening disease. Hydroxyurea and dexamethasone are exceptions and can be taken before the study.

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

Research has shown that tagraxofusp has a mixed safety record. Approximately 3% of patients experienced severe reactions, including capillary leak syndrome (CLS), a potentially fatal condition where fluid leaks from small blood vessels. Additionally, about 8% of patients discontinued treatment due to side effects. Common side effects included increased liver enzymes, indicating possible liver stress.

Despite these concerns, tagraxofusp is approved for treating blastic plasmacytoid dendritic cell neoplasm (BPDCN), suggesting some established safety. Participants should discuss potential risks and benefits with their doctor to make an informed decision. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for acute lymphoblastic leukemia?

Tagraxofusp is unique because it targets a specific protein called CD123, which is often present on the surface of cancer cells in acute lymphoblastic leukemia (ALL). Most current treatments for ALL, like chemotherapy regimens, primarily focus on killing rapidly dividing cells non-selectively, which can affect healthy cells too. Tagraxofusp, on the other hand, is designed to more precisely target leukemia cells, potentially reducing damage to normal cells and leading to fewer side effects. Researchers are excited about this treatment because it offers a new mechanism of action that could improve outcomes for patients who may not respond well to standard therapies.

What evidence suggests that tagraxofusp and chemotherapy might be an effective treatment for acute lymphoblastic leukemia?

Research shows that tagraxofusp holds promise in treating certain cancers. It has proven effective against a rare cancer called blastic plasmacytoid dendritic-cell neoplasm (BPDCN). Tagraxofusp targets a specific marker on cancer cells, CD123, and delivers a substance that kills these cells. Early results indicate that patients treated with tagraxofusp often experience significant tumor shrinkage. In this trial, participants will receive tagraxofusp combined with chemotherapy to evaluate its potential for treating acute lymphoblastic leukemia (ALL). Although this treatment is new for ALL, its success in similar conditions suggests it could benefit patients with CD123 positive relapsed or refractory ALL. ^{3 6 7 8 9}

Who Is on the Research Team?

Nicholas Short

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults aged 18-70 with CD123 positive relapsed or refractory acute lymphoblastic leukemia or lymphoblastic lymphoma can join. They must have certain normal blood test results, no serious heart, liver, lung diseases, HIV, hepatitis B/C and agree to use effective birth control. Pregnant women and those with other life-threatening cancers cannot participate.

Inclusion Criteria

I have taken a pregnancy test within the last week and it was negative.

Serum creatinine =< 1.5 mg/dL

I am willing and able to follow the study's schedule and requirements.

Exclusion Criteria

I have been diagnosed with Philadelphia chromosome-positive ALL or Burkitt leukemia/lymphoma.

I have lasting side effects from past chemotherapy, but not hair loss, tiredness, or liver issues.

I do not have serious heart problems or uncontrolled high blood pressure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Tagraxofusp and Chemotherapy Phase

Patients receive tagraxofusp and chemotherapy drugs in cycles to treat CD123 positive relapsed or refractory acute lymphoblastic leukemia or lymphoblastic lymphoma.

9 cycles (approximately 8 months)

Multiple visits per cycle for drug administration

Tagraxofusp and Maintenance Phase

Patients receive maintenance therapy with tagraxofusp and other drugs to sustain remission.

15 cycles (approximately 15 months)

Monthly visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 3 years

Follow-up at 30 days post-treatment, then every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Dexamethasone
• Tagraxofusp

Trial Overview The trial is testing tagraxofusp combined with low-intensity chemotherapy in patients whose leukemia or lymphoma has returned after treatment or hasn't responded to previous treatments. Tagraxofusp targets cancer cells by linking a toxin to IL3 which is present on the cells' surface.

How Is the Trial Designed?

Group I: Treatment (tagraxofusp, chemotherapy) Experimental Treatment 13 Interventions

See Detailed Description

Tagraxofusp is already approved in United States, European Union for the following indications:

Approved in United States as Elzonris for:

• Blastic plasmacytoid dendritic cell neoplasm (BPDCN)

Approved in European Union as Elzonris for:

• Blastic plasmacytoid dendritic cell neoplasm (BPDCN)

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7448601/

Approval of tagraxofusp-erzs for blastic plasmacytoid ... Tagraxofusp-erzs was the first agent approved for BPDCN (for patients ages 2 years and older), and importantly, established this drug as the first CD123- ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02113982

NCT02113982 | Tagraxofusp in Patients With Blastic ... This is a 4-stage, non-randomized, open-label, dose escalation and expansion, multicenter study. A cycle of therapy is 21 days.

3. ascopubs.org ascopubs.org/doi/10.1200/JCO.22.00034

Long-Term Benefits of Tagraxofusp for Patients With Blastic ... In first-line patients with BPDCN, TAG monotherapy resulted in high and durable responses, allowing many to bridge to stem-cell transplant.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1815105

Tagraxofusp in Blastic Plasmacytoid Dendritic-Cell Neoplasm Tagraxofusp has shown potent antitumor activity against BPDCN cells in both in vitro and in vivo models, with cytotoxicity at femtomolar concentrations.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10887247/

Efficacy and manageable safety of tagraxofusp in blastic ... These cases highlight the efficacy and safety of TAG in pediatric and AYA patients for whom there is no other approved BPDCN therapy.

6. elzonris.com elzonris.com/hcp/safety-profile

Safety Profile | ELZONRIS® (tagraxofusp-erzs) Four (3%) patients had fatal adverse reactions, all of which were related to capillary leak syndrome (CLS).1. Overall, 10 (8%) patients discontinued ...

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/81/NCT04317781/Prot_SAP_000.pdf

Tagraxofusp (SL-401) therapy for blastic plasmacytoid ... 2.3.2 Safety data. The most common individual treatment emergent adverse events (TEAEs) reported to date with tagraxofusp, regardless of dose, were ALT ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2018/761116Orig1s000MedR.pdf

761116Orig1s000 - accessdata.fda.gov Review of Safety. Safety Review Approach. The clinical review of safety for this BLA was based on all available safety data from studies. STML ...

9. targetedonc.com targetedonc.com/view/interpreting-safety-and-efficacy-data-for-tagraxofusp-in-bpdcn

Interpreting Safety and Efficacy Data for Tagraxofusp in ... BORATE: Technically you can continue [indefinitely], until you see intolerable AEs or progression. 1 Most patients end up dose reducing [or] ...