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

Sponsor

University of Maryland, Baltimore (Other)

Overall Status

Recruiting

CT.gov ID

NCT04953780

Collaborator

(none)

Enrollment

Location

Arms

51.1

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Calaspargase pegol-mknl	Phase 1

Detailed Description

This is a multicenter, 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).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

24 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Intervention 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 Leukemia4 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)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 27, 2021

Anticipated Primary Completion Date :

Dec 31, 2025

Anticipated Study Completion Date :

Dec 31, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Calaspargase pegol-mknl dose level 1 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
Experimental: Calaspargase pegol-mknl dose level 2 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
Experimental: Calaspargase pegol-mknl dose level 3 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
Experimental: Calaspargase pegol-mknl dose level 4 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 Calaspargase pegol-mknl

Outcome Measures

Primary Outcome Measures

Primary Outcome Measure [From the first day of treatment until 30 days after receiving Calaspargase Pegol-mknl]
1. Incidence of regimen limiting toxicities (RLTs) and Incidence of treatment-emergent adverse events (TEAE).

Secondary Outcome Measures

1. CR+CRh+CRi [Within 4-8 weeks following completion of induction regimen and completion of consolidation therapy]
Complete remission (CR) + complete remission with partial hematologic recovery (CRh) + complete remission with incomplete count recovery (CRi)
2. The duration of CR/CRh/CRi. [immediately after the intervention]
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. [During the intervention]
Achievement of MRD <0.02% at the end of Induction therapy with Calaspargase pegol-mknl.
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]
Event-free survival (EFS).
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]
Overall survival (OS)
6. Proceeding to allo-HSCT after Calaspargase pegol-mknl treatment [Immediately after the intervention]
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. [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 [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

Other Outcome Measures

Exploratory Endpoint 1 [After the enrollment of the study subjects]
Measurement of asparagine synthetase mRNA and protein expression in patients who have refractory disease or develop relapse
Exploratory Endpoint 2 [After the enrollment of the study subjects]
Measurement of p90RSK expression and phosphorylation of p70S6K, 4EBP1, and eIF4E in bone marrow cells of Calaspargase pegol-mknl treated patients with AML
Exploratory Endpoint 3 [After the enrollment of the study subjects]
Measurement of protein expression of MCL-1, BCL2 and BCL-XL in bone marrow cells of Calaspargase pegol-mknl treated patients with AML.
Exploratory Endpoint 4 [After the enrollment of the study subjects]
Tissue banking for further molecular and functional testing in the future

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Greenebaum Cancer Center, University of Maryland Medical Systems	Baltimore	Maryland	United States	21201

Sponsors and Collaborators

University of Maryland, Baltimore

Investigators

Principal Investigator: Ashkan Emadi, M.D.,Ph.D., University of Maryland, Baltimore

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

University of Maryland, Baltimore

ClinicalTrials.gov Identifier:

NCT04953780

Other Study ID Numbers:

2157GCCC

First Posted:

Jul 8, 2021

Last Update Posted:

Jan 5, 2022

Last Verified:

Dec 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Keywords provided by University of Maryland, Baltimore

Acute Myeloid Leukemia

Additional relevant MeSH terms:

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Study Results

No Results Posted as of Jan 5, 2022