Chemotherapy for Acute Myeloid Leukemia

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effectiveness of a new chemotherapy drug, Calaspargase Pegol-mknl, for individuals with newly diagnosed Acute Myeloid Leukemia (AML). The researchers aim to determine the optimal dose that patients can tolerate without severe side effects. Participants will receive varying doses of the drug alongside other standard chemotherapy medications to identify the most effective dose with the fewest side effects. Individuals diagnosed with AML who experience symptoms like fatigue and frequent infections might be suitable candidates for this trial. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that Calaspargase Pegol-mknl is already FDA-approved for treating Acute Lymphoblastic Leukemia (ALL), indicating general safety for patients. However, this trial tests its use for a different cancer, Acute Myeloid Leukemia (AML), which may present new safety concerns.

In past studies with ALL patients, common side effects included fever, infections, and tiredness. These effects are serious but not unusual for cancer treatments. Since this trial is in its early stages, it aims to determine the safest dose for AML patients. Researchers are closely monitoring side effects to find the best balance between efficacy and safety.

Consulting a doctor is crucial to understand the risks and benefits before joining a trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Calaspargase pegol-mknl is unique because it offers a new approach to treating Acute Myeloid Leukemia (AML) by incorporating pegylated asparaginase, which helps break down asparagine, a nutrient cancer cells need to grow. Unlike the standard chemotherapy options like Cytarabine and Idarubicin, Calaspargase pegol-mknl is designed to be longer-lasting due to its pegylation, potentially reducing the frequency of doses needed. Researchers are excited because this could mean fewer side effects and a more convenient treatment schedule for patients, while still effectively targeting cancer cells.

What evidence suggests that this trial's treatments could be effective for Acute Myeloid Leukemia?

Research shows that Calaspargase Pegol-mknl is under investigation as a potential treatment for Acute Myeloid Leukemia (AML) in this trial. Participants will receive varying doses of Calaspargase Pegol-mknl across different treatment arms. This drug breaks down an essential amino acid called asparagine, which cancer cells require for survival. By depleting asparagine, it may starve leukemia cells and inhibit their growth. Early results from similar treatments suggest that depriving cancer cells of essential nutrients can effectively combat certain types of leukemia. Although data on Calaspargase Pegol-mknl specifically for AML is limited, the method appears promising based on the success of similar treatments in other leukemia types. ^{2 4 6 7 8}

Who Is on the Research Team?

Ashkan Emadi, MD, PhD

Principal Investigator

West Virginia University

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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).

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03959085

Study Details | NCT03959085 | Inotuzumab Ozogamicin ... The overall goal of this study is to understand if adding inotuzumab ozogamicin to standard of care chemotherapy maintains or improves outcomes in High Risk B- ...

2. clinicaltrials.stanford.edu clinicaltrials.stanford.edu/trials/i/NCT03959085.html

Inotuzumab Ozogamicin and Post-Induction Chemotherapy in ... This trial will also study the outcomes of patients with mixed phenotype acute leukemia (MPAL) and disseminated B lymphoblastic lymphoma (B-LLy) when treated ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02981628

Study Details | NCT02981628 | Inotuzumab Ozogamicin in ... This phase II trial studies how well inotuzumab ozogamicin works in treating younger patients with B-lymphoblastic lymphoma or CD22 positive B acute ...

4. clinicaltrial.be clinicaltrial.be/en/details/63549?per_page=100&only_recruiting=0&only_eligible=0&only_active=0

Inotuzumab Ozogamicin and Post-Induction Chemotherapy ... To describe the 5-year event-free survival (EFS) for patients with mixed phenotype acute leukemia (MPAL) receiving mBFM HR B-ALL therapy that includes a second ...

5. med.stanford.edu med.stanford.edu/content/sm/sleepdivision/research/clinicaltrials/results.html?start=2740

Clinical Trials results | Division of Sleep Medicine | Stanford Medicine This phase 2 trial studies how well ixazomib(MLN9708) works in treating study participants with relapsed or refractory acute myeloid leukemia. Ixazomib may stop ...

6. besponsa.pfizerpro.com besponsa.pfizerpro.com/safety/adult-safety-data

BESPONSA® (inotuzumab ozogamicin) Safety Information The most common (≥2%) serious adverse reactions (ARs) were infection, febrile neutropenia, hemorrhage, abdominal pain, pyrexia, VOD, and fatigue · References.

7. cda-amc.ca cda-amc.ca/sites/default/files/DRR/2024/PC0321-Asparlas-Combined-Report.pdf

Calaspargase Pegol (Asparlas) ... safety data (data cut-off date of February 1, 2017) ... FDA Approval Summary: Calaspargase Pegol-mknl For Treatment of Acute Lymphoblastic Leukemia in.

8. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK604418/

Pharmacoeconomic Review - Calaspargase Pegol (Asparlas) The majority of the respondents (n = 47) identified as patients with acute lymphoblastic leukemia (ALL) and 20 respondents indicated they were caregivers of ...