What is the mechanism of action of this treatment?

Common treatments for Acute Myeloid Leukemia (AML) include chemotherapeutic agents like cytarabine and idarubicin, which are often used in combination. Cytarabine is a nucleoside analog that interferes with DNA synthesis, leading to the inhibition of DNA replication and cell division, which is crucial for rapidly dividing cancer cells. Idarubicin, an anthracycline antibiotic, intercalates into DNA, disrupting the enzyme topoisomerase II, which is essential for DNA repair and replication. This results in DNA damage and apoptosis of cancer cells. These mechanisms are vital for AML patients as they target the uncontrolled proliferation of leukemic cells, aiming to induce remission and prevent disease progression.

What side effects are associated with this type of intervention?

Common treatments for Acute Myeloid Leukemia (AML) include chemotherapeutic agents such as cytarabine and idarubicin. These treatments often lead to side effects like myelosuppression, which can result in neutropenia, increasing the risk of infections. Other frequent side effects include nausea, vomiting, mucositis, and alopecia. Additionally, patients may experience cardiotoxicity, particularly with anthracyclines like idarubicin. Managing these side effects is crucial to ensure the patient's safety and improve treatment outcomes.

What prior FDA approvals exist?

The FDA has approved several treatments for Acute Myeloid Leukemia (AML) that interfere with cancer cell growth and proliferation. Hypomethylating agents (HMAs) such as azacitidine and decitabine are commonly used and have shown comparable efficacy. These agents are often combined with other drugs like venetoclax, which enhances their effectiveness. Additionally, ivosidenib has been approved for use in combination with HMAs for specific genetic mutations in AML. These treatments aim to inhibit the growth and proliferation of cancer cells, similar to the mechanism of action of Calaspargase Pegol-mknl.

What other types of research exist?

Promising novel alternatives to Calaspargase Pegol-mknl for AML patients include: 1) Venetoclax in combination with hypomethylating agents (e.g., azacitidine or decitabine), which has shown significant efficacy in elderly or unfit AML patients. 2) Gilteritinib, a FLT3 inhibitor, for patients with FLT3-mutated AML. 3) CPX-351 (Vyxeos), a liposomal formulation of daunorubicin and cytarabine, which has been approved for secondary AML and has shown improved outcomes compared to traditional chemotherapy. These alternatives offer targeted mechanisms and have demonstrated promising results in clinical trials.

← Back to Search

Enzyme

Chemotherapy for Acute Myeloid Leukemia

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

Age 18-65 years old

ECOG performance status < 3

Must not have

Pregnant women and female patients who are lactating and do not agree to stop breast-feeding

Unprovoked DVT

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from the first date of intervention until the first documented progression or the date of death from any causes, whichever came first, assessed up to 100 months

Awards & highlights

No Placebo-Only Group

Summary

This trial tests Calaspargase Pegol-mknl, a chemotherapy drug, in adult patients with newly diagnosed AML. It aims to find the safest effective dose by administering the drug through an IV to target cancer cells. Calaspargase Pegol-mknl is a newer chemotherapeutic agent used for treating acute lymphoblastic leukemia, similar to pegaspargase.

Who is the study for?

This trial is for adults aged 18-65 with newly diagnosed AML who can attend required visits, have normal organ function, and agree to use non-hormonal contraception. Excluded are those with severe pancreatitis unrelated to gallstones, unprovoked blood clots or strokes, major bleeding events recently, hypersensitivity to similar drugs, other treatments for cancer ongoing or certain genetic abnormalities in their leukemia.

What is being tested?

The study tests Calaspargase Pegol-mknl as a chemotherapy agent for AML patients. It aims to find the highest dose patients can take without serious side effects (MTD) and decide on a recommended dose for future Phase 2 trials (RP2D).

What are the potential side effects?

Potential side effects of Calaspargase Pegol-mknl may include allergic reactions due to its pegylated nature, liver dysfunction indicated by elevated bilirubin levels, abnormal blood clotting leading to thrombosis or stroke risks, and possible impact on heart function.

Eligibility Criteria

Inclusion Criteria

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

Select...

I am between 18 and 65 years old.

Select...

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

Select...

My diagnosis of AML is confirmed by lab tests.

Exclusion Criteria

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

Select...

I am not pregnant or breastfeeding, or I agree to stop breastfeeding if I am.

Select...

I have had a blood clot in my leg that occurred without any clear reason.

Select...

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

Select...

I have had a stroke caused by bleeding or blood clots.

Select...

I have had a serious blood clot.

Select...

I have bleeding issues due to low platelet counts from my AML.

Select...

I have a bleeding disorder.

Select...

I have had severe pancreatitis not caused by gallstones.

Select...

My AML has specific genetic changes.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from the first date of intervention until the first documented progression or the date of death from any causes, whichever came first, assessed up to 100 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from the first date of intervention until the first documented progression or the date of death from any causes, whichever came first, assessed up to 100 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and from the first date of intervention until the first documented progression or the date of death from any causes, whichever came first, assessed up to 100 months for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Measure

Secondary study objectives

1. CR+CRh+CRi

2. The duration of CR/CRh/CRi.

3. Achievement of MRD <0.02% at the end of Induction therapy with Calaspargase pegol-mknl.

+5 more

Other study objectives

Exploratory Endpoint 1

Exploratory Endpoint 2

Exploratory Endpoint 3

+1 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: Calaspargase pegol-mknl dose level 4Experimental Treatment1 Intervention

Induction Phase (It usually lasts 29 days): * The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses. * The subject will take Idarubicin 12 mg/m2 for three doses in an IV after the first, third, and fifth High-dose Cytarabine. * The subject will take a dose of 2,000 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine every 21 days ( per cycle). Consolidation Phase ( One cycle of consolidation lasts 4-8 weeks): * The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses. * The subject will take a dose of 2,000 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine per cycle. * A single cycle of consolidation may last between 4-8 weeks in duration.

Group II: Calaspargase pegol-mknl dose level 3Experimental Treatment1 Intervention

Induction Phase (It usually lasts 29 days): * The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses. * The subject will take Idarubicin 12 mg/m2 for three doses in an IV after the first, third, and fifth High- dose Cytarabine. * The subject will take a dose of 1,500 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine every 21 days ( per cycle). Consolidation Phase ( One cycle of consolidation lasts 4-8 weeks): * The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses. * The subject will take a dose of 1,500 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine. * A single cycle of consolidation may last between 4-8 weeks in duration.

Group III: Calaspargase pegol-mknl dose level 2Experimental Treatment1 Intervention

Induction Phase (It usually lasts 29 days): * The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses. * The subject will take Idarubicin 12 mg/m2 for three doses in an IV after the first, third, and fifth High-dose Cytarabine. * The subject will take a dose of 1,000 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine every 21 days ( per cycle). Consolidation Phase ( One cycle of consolidation lasts 4-8 weeks): * The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses. * The subject will take a dose of 1,000 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine(every 21 days ( per cycle). * A single cycle of consolidation may last between 4-8 weeks in duration.

Group IV: Calaspargase pegol-mknl dose level 1Experimental Treatment1 Intervention

Induction Phase (It usually lasts 29 days): * The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses. * The subject will take Idarubicin 12 mg/m2 for three doses in an IV after the first, third, and fifth High-dose Cytarabine. * The subject will take a dose of 750 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine every 21 days ( per cycle). Consolidation Phase ( One cycle of consolidation lasts 4-8 weeks): * The subject will take Cytarabine 3000 mg/m2 in an IV every 12 hours on days 1, 3, 5 for 6 doses. * The subject will take a dose of 750 U/m2 of Calaspargase pegol-mknl in an IV after the last (6th) dose of High-dose Cytarabine. * A single cycle of consolidation may last between 4-8 weeks in duration.

0 / 12Eligibility 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

Common treatments for Acute Myeloid Leukemia (AML) include chemotherapeutic agents like cytarabine and idarubicin, which are often used in combination. Cytarabine is a nucleoside analog that interferes with DNA synthesis, leading to the inhibition of DNA replication and cell division, which is crucial for rapidly dividing cancer cells. Idarubicin, an anthracycline antibiotic, intercalates into DNA, disrupting the enzyme topoisomerase II, which is essential for DNA repair and replication. This results in DNA damage and apoptosis of cancer cells. These mechanisms are vital for AML patients as they target the uncontrolled proliferation of leukemic cells, aiming to induce remission and prevent disease progression.