What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) include asparagine depletion agents like Pegcrisantaspase and BCL-2 inhibitors like Venetoclax. Pegcrisantaspase can cause side effects such as thrombosis, prolonged prothrombin time, and hypofibrinogenemia. Venetoclax is associated with neutropenia, infections, and gastrointestinal symptoms. Hypomethylating agents (HMAs) like azacitidine and decitabine can lead to myelosuppression, infections, and gastrointestinal issues. Low-dose cytarabine (LDAC) is often linked to hematologic toxicities such as neutropenia and thrombocytopenia. These treatments aim to manage AML but come with significant side effects that require careful monitoring.

What prior FDA approvals exist?

Venetoclax, a BCL-2 inhibitor, has been FDA-approved for use in combination with hypomethylating agents like azacitidine or decitabine for newly diagnosed AML in patients ineligible for intensive chemotherapy. Other related FDA-approved drugs include ivosidenib (IDH1 inhibitor) and midostaurin (FLT3 inhibitor), which target specific genetic mutations in AML. These approvals reflect a shift towards targeted and combination therapies in the treatment of AML.

What other types of research exist?

Promising novel alternatives for AML treatment include: 1) Imetelstat, an investigational antisense oligonucleotide targeting telomerase, which has shown partial and complete responses in advanced myelofibrosis and may have potential in AML. 2) Immune checkpoint inhibitors such as anti-PD-1 or anti-CTLA-4 antibodies, which are being explored for their efficacy in various hematologic malignancies. 3) Novel tyrosine kinase inhibitors targeting specific mutations, such as FLT3 inhibitors (e.g., gilteritinib) for FLT3-mutated AML. These alternatives offer different mechanisms of action and may provide new therapeutic options for AML patients.

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Enzyme

Pegcrisantaspase + Venetoclax for Acute Myeloid Leukemia

Q: What is the mechanism of action of this treatment?

Pegcrisantaspase depletes asparagine, an amino acid necessary for leukemia cell survival, thereby inhibiting their growth. Venetoclax inhibits BCL-2, a protein that prevents apoptosis in cancer cells, promoting their death. These mechanisms are crucial for AML patients as they specifically target and kill leukemia cells, potentially improving treatment outcomes and survival rates.

Phase 1

Waitlist Available

Led By Vu Duong, MD

Research Sponsored by University of Maryland, Baltimore

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

AML has relapsed after or is refractory to, first-line therapy, with a maximum of three prior lines of therapy. Patients whose AML has FLT3 or IDH1/IDH2 mutations should have received at least one available FLT3 or IDH1/IDH2 inhibitors

Age 18 years and older

Must not have

Patients with acute promyelocytic leukemia (APL) confirmed with t(15;17) (i.e. FAB subtype M3 and M3 variant)

Patients receiving any other investigational agents, or concurrent chemotherapy or immunotherapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up one year (after 12 cycle's treatment)

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a combination treatment for adults with a hard-to-treat type of blood cancer. The treatment involves regular pills and injections. It aims to kill cancer cells and starve them of essential nutrients.

Who is the study for?

Adults diagnosed with relapsed or refractory acute myeloid leukemia (R/R AML) who have tried up to three prior treatments. Suitable for those with certain genetic mutations if they've had specific inhibitors, and post stem cell transplant patients without severe graft versus host disease. Must not have other active cancers, recent investigational drug use, or uncontrolled illnesses.

What is being tested?

The trial is testing the combination of two drugs: Venetoclax and pegcrisantaspase (Ven-PegC), in adults with R/R AML to find safe dosage levels and assess tolerability. It aims to determine the maximum doses that do not cause unacceptable side effects.

What are the potential side effects?

Potential side effects may include reactions at the infusion site, liver abnormalities, pancreatitis, blood clotting issues like deep vein thrombosis or stroke, infections due to weakened immune system response, and possibly others related to organ function.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My AML has returned or didn't respond to 1-3 treatments. I've tried FLT3 or IDH inhibitors if applicable.

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I am 18 years old or older.

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My AML diagnosis is confirmed and fits specific genetic features.

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I can take care of myself but might not be able to do heavy physical work.

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I had a stem cell transplant over 30 days ago, no serious GVHD, and stopped immunosuppressants for 10+ days.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My leukemia is a specific type known as APL with a certain genetic feature.

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I am not currently on any experimental drugs or receiving chemotherapy or immunotherapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ one year (after 12 cycle's treatment)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~one year (after 12 cycle's treatment)

This trial's timeline: 3 weeks for screening, Varies for treatment, and one year (after 12 cycle's treatment) for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of regimen limiting toxicities (RLTs)

Incidence of treatment-emergent adverse events (TEAE)

Secondary study objectives

Achievement of MRD <0.02% within 2 cycles of treatment with Ven-PegC

Event-free Survival (EFS)

Overall Survival (OS)

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

4Treatment groups

Experimental Treatment

Group I: Cohort 600mg Venetoclax, 1000 IU/m ² of PegcrisantaspaseExperimental Treatment1 Intervention

The subject will take 600mg of Venetoclax every day as a pill by mouth and a dose of 1000 IU/m ² of Pegcrisantaspase in an IV every 14 days ( Per cycle)

Group II: Cohort 400mg of Venetoclax, 750 IU/m ² of PegcrisantaspaseExperimental Treatment1 Intervention

The subject will take 400mg of Venetoclax every day as a pill by mouth and a dose of 750 IU/m ² of Pegcrisantaspase in an IV every 14 days ( per cycle)

Group III: Cohort 400mg of Venetoclax, 500 IU/m ² of PegcrisantaspaseExperimental Treatment1 Intervention

The subject will take 400mg of Venetoclax every day as a pill by mouth and a dose of 500 IU/m ² of Pegcrisantaspase in an IV every 14 days ( per cycle)

Group IV: Cohort 400mg of Venetoclax, 1000 IU/m² of PegcrisantaspaseExperimental Treatment1 Intervention

The subject will take 400mg of Venetoclax every day as a pill by mouth and a dose of 1000 IU/m² of Pegcrisantaspase in an IV every 14 days ( per cycle)

0 / 7Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Pegcrisantaspase depletes asparagine, an amino acid necessary for leukemia cell survival, thereby inhibiting their growth. Venetoclax inhibits BCL-2, a protein that prevents apoptosis in cancer cells, promoting their death. These mechanisms are crucial for AML patients as they specifically target and kill leukemia cells, potentially improving treatment outcomes and survival rates.

Synergistic effect of chidamide and venetoclax on apoptosis in acute myeloid leukemia cells and its mechanism.Cotargeting BCL-2 and PI3K Induces BAX-Dependent Mitochondrial Apoptosis in AML Cells.