Chemotherapy for Acute Myeloid Leukemia

Recruiting at 1 trial location

Overseen By Sunita Philip

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: West Virginia University

Must not be taking: Investigational agents, Chemotherapy

Disqualifiers: Pancreatitis, Stroke, Thrombosis, 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: Unknown

6 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

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 does mention that you cannot be on other investigational agents or concurrent chemotherapy or immunotherapy. Hydroxyurea is allowed for a short period before and after starting the trial treatment.

What data supports the effectiveness of the drug Calaspargase Pegol-mknl, Inotuzumab Ozogamicin, Besponsa for treating acute myeloid leukemia?

Research shows that a similar drug, gemtuzumab ozogamicin, when combined with other chemotherapy drugs, improved survival rates and reduced the risk of relapse in patients with acute myeloid leukemia. This suggests that antibody-drug conjugates like Inotuzumab Ozogamicin, which is similar in nature, may also be effective in treating this condition. ^{1 2 3 4 5}

Is gemtuzumab ozogamicin safe for treating acute myeloid leukemia?

Gemtuzumab ozogamicin (GO) has been associated with serious side effects, including liver problems and infusion reactions. However, using a lower-dose schedule has shown fewer side effects like early death and liver issues, making it safer for some patients. ^{2 6 7 8 9}

Research Team

Ashkan Emadi, MD, PhD

Principal Investigator

West Virginia University

Eligibility Criteria

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.

Inclusion Criteria

Ability to understand and willingness to sign a written informed consent document

I am not pregnant and agree to use effective birth control during the study.

Normal organ function criteria: Total bilirubin ≤2X the institutional upper limit of normal (ULN) (except in patients with leukemic infiltration of the liver), AST(SGOT)/ALT(SGPT) ≤3X ULN (except if attributable to leukemic infiltration of the liver), Creatinine Clearance (CrCl) ≥ 40 mL/min (except in patients with evidence of tumor lysis syndrome), Left ventricular ejection fraction (LVEF) ≥50%

Exclusion Criteria

History of serious hypersensitivity reactions to pegylated L-asparaginase therapy

PE

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

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction

High-dose Cytarabine, Idarubicin, and Calaspargase Pegol-mknl are administered to determine regimen-limiting toxicities

4 weeks

Multiple visits for drug administration

Consolidation

High-dose Cytarabine and Calaspargase Pegol-mknl are administered to consolidate remission

4-8 weeks

Multiple visits for drug administration

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Calaspargase Pegol-mknl

Trial Overview 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).

Participant Groups

Group I: Calaspargase pegol-mknl dose level 4 Experimental Treatment 1 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 3 Experimental Treatment 1 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 2 Experimental Treatment 1 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 1 Experimental Treatment 1 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.

Calaspargase Pegol-mknl is already approved in European Union, United States for the following indications:

Approved in European Union as Besponsa for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL)

Approved in United States as Besponsa for:

• Relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients 1 year and older

Who Is Running the Clinical Trial?

West Virginia University

Lead Sponsor

Trials

192

Recruited

64,700+

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Findings from Research

Gemtuzumab ozogamicin (Mylotarg) has been approved for treating acute myeloid leukemia (AML) in patients aged 15 and older, showing significant improvements in event-free survival and reduced relapse risk based on a meta-analysis of 3,325 patients.

While Mylotarg is effective, it is associated with common side effects such as hemorrhage and infection, particularly when used in combination with other chemotherapy drugs like daunorubicin and cytarabine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The EMA Review of Mylotarg (Gemtuzumab Ozogamicin) for the Treatment of Acute Myeloid Leukemia. Ali, S., Dunmore, HM., Karres, D., et al.[2020]

Gemtuzumab ozogamicin, when combined with daunorubicin and cytarabine, significantly improved event-free survival in adults with newly diagnosed CD33-positive acute myeloid leukemia (AML), with a median EFS of 13.6 months compared to 8.8 months for the standard treatment alone.

As a monotherapy, gemtuzumab ozogamicin also showed improved overall survival (4.9 months) compared to best supportive care (3.6 months), although serious side effects like hemorrhage and prolonged thrombocytopenia were more common with the combination treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval: Gemtuzumab Ozogamicin for the Treatment of Adults with Newly Diagnosed CD33-Positive Acute Myeloid Leukemia. Jen, EY., Ko, CW., Lee, JE., et al.[2019]

References

1. England pubmed.ncbi.nlm.nih.gov

The EMA Review of Mylotarg (Gemtuzumab Ozogamicin) for the Treatment of Acute Myeloid Leukemia. [2020]

2. England pubmed.ncbi.nlm.nih.gov

Effect of adding gemtuzumab ozogamicin to induction chemotherapy for newly diagnosed acute myeloid leukemia: a meta-analysis of prospective randomized phase III trials. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Gemtuzumab ozogamicin and novel antibody-drug conjugates in clinical trials for acute myeloid leukemia. [2023]

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

Identification of patients with acute myeloblastic leukemia who benefit from the addition of gemtuzumab ozogamicin: results of the MRC AML15 trial. [2022]

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

FDA Approval: Gemtuzumab Ozogamicin for the Treatment of Adults with Newly Diagnosed CD33-Positive Acute Myeloid Leukemia. [2019]

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

What role does gemtuzumab ozogamicin have in the treatment of acute myelogenous leukemia? [2021]

7. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Mylotarg for Treatment of Patients with Relapsed or Refractory CD33-Positive Acute Myeloid Leukemia. [2019]

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

Gemtuzumab ozogamicin for treatment of newly diagnosed acute myeloid leukaemia: a systematic review and meta-analysis. [2019]

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

Gemtuzumab ozogamicin for treatment of newly diagnosed CD33-positive acute myeloid leukemia. [2023]