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

Primary Purpose

Acute Myeloid Leukemia

Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Calaspargase pegol-mknl
Sponsored by
University of Maryland, Baltimore
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute Myeloid Leukemia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
    • PE
    • 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

Sites / Locations

  • Greenebaum Cancer Center, University of Maryland Medical SystemsRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Experimental

Experimental

Arm Label

Calaspargase pegol-mknl dose level 1

Calaspargase pegol-mknl dose level 2

Calaspargase pegol-mknl dose level 3

Calaspargase pegol-mknl dose level 4

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

1. CR+CRh+CRi
Complete remission (CR) + complete remission with partial hematologic recovery (CRh) + complete remission with incomplete count recovery (CRi)
2. The duration of CR/CRh/CRi.
The duration of Complete remission (CR) / complete remission with partial hematologic recovery (CRh) / complete remission with incomplete count recovery (CRi)
3. Achievement of MRD <0.02% at the end of Induction therapy with Calaspargase pegol-mknl.
Achievement of MRD <0.02% at the end of Induction therapy with Calaspargase pegol-mknl.
4. Event-free survival (EFS).
Event-free survival (EFS).
5. Overall survival (OS)
Overall survival (OS)
6. Proceeding to allo-HSCT after Calaspargase pegol-mknl treatment
Proceeding to allo-HSCT after Calaspargase pegol-mknl treatment
7. Plasma asparagine and glutamine and other amino acids levels at baseline and weekly after administration of Calaspargase pegol-mknl. for four weeks.
Plasma asparagine and glutamine and other amino acids levels at baseline and weekly after administration of Calaspargase pegol-mknl. for four weeks.
8.Plasma asparaginase activity at baseline and weekly after administration of Calaspargase pegol-mknl for four weeks
Plasma asparaginase activity at baseline and weekly after administration of Calaspargase pegol-mknl for four weeks

Full Information

First Posted
June 15, 2021
Last Updated
August 6, 2023
Sponsor
University of Maryland, Baltimore
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1. Study Identification

Unique Protocol Identification Number
NCT04953780
Brief Title
2157GCCC:Phase 1 of Calaspargase Pegol-mknl w/ Cytarabine and Idarubicin in Newly Dx AML
Official Title
2157GCCC: A Phase I Trial of Calaspargase Pegol-mknl in Combination With High Dose Cytarabine and Idarubicin in Adult Patients With Newly Diagnosed Acute Myeloid Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 27, 2021 (Actual)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Maryland, Baltimore

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
This is a single center, non-randomized, open-label, phase I study evaluating regimen-limiting toxicities of Calaspargase Pegol-mknl administered intravenously in Adult Patients with Newly Diagnosed Acute Myeloid Leukemia (AML). The trial will consist of the induction and consolidation phases of therapy. At the induction phase ( it usually lasts for 29 days): a high-dose of Cytarabine will be administered IV for six doses, plus Idarubicin administered IV for three doses and Calaspargase Pegol-mknl administered IV one dose, using a dose-escalation scheme. At the consolidation phase (single cycle of consolidation lasts 4-8 weeks): a high-dose of Cytarabine will be administered IV for six doses, and Calaspargase Pegol-mknl administered IV for one dose, using a dose-escalation scheme. The FDA (The US Food and Drug Administration) has not approved Calaspargase Pegol-mknl for Adult Patients with Newly Diagnosed Acute Myeloid Leukemia (AML).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Myeloid Leukemia
Keywords
Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Model Description
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
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
24 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Calaspargase pegol-mknl dose level 1
Arm Type
Experimental
Arm Description
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.
Arm Title
Calaspargase pegol-mknl dose level 2
Arm Type
Experimental
Arm Description
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.
Arm Title
Calaspargase pegol-mknl dose level 3
Arm Type
Experimental
Arm Description
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.
Arm Title
Calaspargase pegol-mknl dose level 4
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Calaspargase pegol-mknl
Intervention Description
Calaspargase pegol-mknl
Primary Outcome Measure Information:
Title
Primary Outcome Measure
Description
1. Incidence of regimen limiting toxicities (RLTs) and Incidence of treatment-emergent adverse events (TEAE).
Time Frame
From the first day of treatment until 30 days after receiving Calaspargase Pegol-mknl
Secondary Outcome Measure Information:
Title
1. CR+CRh+CRi
Description
Complete remission (CR) + complete remission with partial hematologic recovery (CRh) + complete remission with incomplete count recovery (CRi)
Time Frame
Within 4-8 weeks following completion of induction regimen and completion of consolidation therapy
Title
2. The duration of CR/CRh/CRi.
Description
The duration of Complete remission (CR) / complete remission with partial hematologic recovery (CRh) / complete remission with incomplete count recovery (CRi)
Time Frame
immediately after the intervention
Title
3. Achievement of MRD <0.02% at the end of Induction therapy with Calaspargase pegol-mknl.
Description
Achievement of MRD <0.02% at the end of Induction therapy with Calaspargase pegol-mknl.
Time Frame
During the intervention
Title
4. Event-free survival (EFS).
Description
Event-free survival (EFS).
Time Frame
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
Title
5. Overall survival (OS)
Description
Overall survival (OS)
Time Frame
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
Title
6. Proceeding to allo-HSCT after Calaspargase pegol-mknl treatment
Description
Proceeding to allo-HSCT after Calaspargase pegol-mknl treatment
Time Frame
Immediately after the intervention
Title
7. Plasma asparagine and glutamine and other amino acids levels at baseline and weekly after administration of Calaspargase pegol-mknl. for four weeks.
Description
Plasma asparagine and glutamine and other amino acids levels at baseline and weekly after administration of Calaspargase pegol-mknl. for four weeks.
Time Frame
At baseline and weekly after administration of Calaspargase pegol-mknl for four weeks
Title
8.Plasma asparaginase activity at baseline and weekly after administration of Calaspargase pegol-mknl for four weeks
Description
Plasma asparaginase activity at baseline and weekly after administration of Calaspargase pegol-mknl for four weeks
Time Frame
At baseline and weekly after administration of Calaspargase pegol-mknl for four weeks
Other Pre-specified Outcome Measures:
Title
Exploratory Endpoint 1
Description
Measurement of asparagine synthetase mRNA and protein expression in patients who have refractory disease or develop relapse
Time Frame
After the enrollment of the study subjects
Title
Exploratory Endpoint 2
Description
Measurement of p90RSK expression and phosphorylation of p70S6K, 4EBP1, and eIF4E in bone marrow cells of Calaspargase pegol-mknl treated patients with AML
Time Frame
After the enrollment of the study subjects
Title
Exploratory Endpoint 3
Description
Measurement of protein expression of MCL-1, BCL2 and BCL-XL in bone marrow cells of Calaspargase pegol-mknl treated patients with AML.
Time Frame
After the enrollment of the study subjects
Title
Exploratory Endpoint 4
Description
Tissue banking for further molecular and functional testing in the future
Time Frame
After the enrollment of the study subjects

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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 PE 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ashkan Emadi, M.D.,Ph.D.
Phone
410-328-6841
Email
aemadi@umm.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Sunita Philip
Phone
410-328-8199
Email
sphilip1@umm.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ashkan Emadi, M.D.,Ph.D.
Organizational Affiliation
University of Maryland, Baltimore
Official's Role
Principal Investigator
Facility Information:
Facility Name
Greenebaum Cancer Center, University of Maryland Medical Systems
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Philip Sunita
Phone
410-328-8199
Email
sphilip1@umm.edu
First Name & Middle Initial & Last Name & Degree
Larissa Sanglard
Phone
410-328-8199
Email
Larissa.Sanglard@umm.edu

12. IPD Sharing Statement

Plan to Share IPD
No
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2157GCCC:Phase 1 of Calaspargase Pegol-mknl w/ Cytarabine and Idarubicin in Newly Dx AML

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