2157GCCC:Phase 1 of Calaspargase Pegol-mknl W/ Cytarabine and Idarubicin in Newly Dx AML

NCT04953780 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 2502110131
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief Summary

Characterizing the regimen limiting toxicity (RLT) of chemotherapeutic drug Calaspargase Pegol-mknl as remission induction and consolidation chemotherapy in patients with newly diagnosed Acute Myeloid Leukemia (AML) and Identifying the Maximum Tolerated Dose (MTD) and Recommended Phase 2 Dose (RP2D) of Calaspargase Pegol-mknl.

Conditions

Acute Myeloid Leukemia

Keywords

Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measure

  1\. Incidence of regimen limiting toxicities (RLTs) and Incidence of treatment-emergent adverse events (TEAE).

  From the first day of treatment until 30 days after receiving Calaspargase Pegol-mknl

Secondary Outcomes (8)

• 1. CR+CRh+CRi

  Within 4-8 weeks following completion of induction regimen and completion of consolidation therapy

• 2. The duration of CR/CRh/CRi.

  immediately after the intervention

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

  During the intervention

• 4. Event-free survival (EFS).

  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

• 5. Overall survival (OS)

  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

Other Outcomes (4)

• Exploratory Endpoint 1

  After the enrollment of the study subjects

• Exploratory Endpoint 2

  After the enrollment of the study subjects

• Exploratory Endpoint 3

  After the enrollment of the study subjects

Study Arms (4)

Calaspargase pegol-mknl dose level 1

EXPERIMENTAL

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.

Drug: Calaspargase pegol-mknl

Calaspargase pegol-mknl dose level 2

EXPERIMENTAL

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.

Drug: Calaspargase pegol-mknl

Calaspargase pegol-mknl dose level 3

EXPERIMENTAL

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.

Drug: Calaspargase pegol-mknl

Calaspargase pegol-mknl dose level 4

EXPERIMENTAL

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.

Drug: Calaspargase pegol-mknl

Interventions

Calaspargase pegol-mknl DRUG

Calaspargase pegol-mknl

Calaspargase pegol-mknl dose level 1; Calaspargase pegol-mknl dose level 2; Calaspargase pegol-mknl dose level 3; Calaspargase pegol-mknl dose level 4

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A histologically or pathologically confirmed diagnosis of AML based on WHO classification. Patients with myelodysplastic syndromes (MDS) or myeloproliferative neoplasms (MPN) evolving into AML who are candidates for AML induction therapy are eligible for enrollment.
• Age 18-65 years old.
• ECOG performance status \< 3.
• Patients must have normal organ function as defined below:
• 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%
• Female patients of childbearing potential must have a negative pregnancy test \<1 week before enrollment. Female patients of childbearing potential who are sexually active and male patients who are sexually active and have female partners of childbearing potential must agree to use a highly effective method of non-hormonal contraception. Contraception should be used during treatment and for at least 3 months after the last dose of Calaspargase pegol-mknl.
• Ability to understand and willingness to sign a written informed consent document.
• Agree to comply with the study requirements and agrees to come to the clinic/hospital for required study visits

You may not qualify if:

• Patients with the following clinical histories are excluded:
• severe pancreatitis not related to cholelithiasis. Severe acute pancreatitis as defined by lipase elevation \>5X ULN and with signs or symptoms
• unprovoked DVT
• serious or life-threatening thrombosis in any location of the body
• hemorrhagic or thromboembolic stroke
• major hemorrhagic event within three weeks before signing ICF; hemorrhage due to thrombocytopenia from underlying AML is excluded
• patients with hemorrhagic diathesis
• neurologic/cerebellar disorders that may confound the toxicity monitoring of HiDAC
• history of serious hypersensitivity reactions to pegylated L-asparaginase therapy
• Patients receiving any other investigational agents or concurrent chemotherapy or immunotherapy. Hydroxyurea for blast count control is permitted before starting treatment and up to a maximum of 10 days after starting treatment on the study.
• Patients with AML with any of the following cytogenetic abnormalities: t(15;17), t(8;21), inv(16), t(16;16).
• Pregnant women and female patients who are lactating and do not agree to stop breast-feeding.
• Uncontrolled undercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled active seizure disorder, or psychiatric illness/social situations that per site Principal Investigator's judgment would limit compliance with study requirements

Sponsors & Collaborators

• West Virginia University: lead

Study Sites (2)

Greenebaum Cancer Center, University of Maryland Medical Systems

Baltimore, Maryland, 21201, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Related Publications (33)

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MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

calaspargase pegol

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Ashkan Emadi, MD, PhD

  West Virginia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Alexander Bland Osborn Endowed Chair and Distinguished Professor of Medical Oncology

Model Details: 4 parallel-arm study of the different dose of Calaspargase Pegol-mknl with combination with High Dose Cytarabine and /or Idarubicin in Adult Patients with Newly Diagnosed Acute Myeloid Leukemia

Study Record Dates

• First Submitted: June 15, 2021
• First Posted: July 8, 2021
• Study Start: September 27, 2021
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: March 6, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)