Back to resultsCalaspargase Pegol in Adults With ALL
Primary Purpose
Acute Lymphoblastic Leukemia
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Calaspargase pegol (S95015)
Sponsored by
About this trial
This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring Acute Lymphoblastic Leukemia, ALL, Ph-negative B-cell and T cell ALL, Philadelphia-negative ALL, Calaspargase Pegol, Asparlas, Adult, Acute Lymphocytic Leukemia, Newly diagnosed ALL, Untreated ALL
Eligibility Criteria
Inclusion Criteria:
- Aged ≥22 years with newly-diagnosed and cytologically confirmed and documented Philadelphia-negative B-cell or T-cell ALL by World Health Organization (WHO) classification (2016).
- Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2.
- No prior therapy for ALL such as chemotherapy and radiation therapy before signing the informed consent except for limited treatment (≤7 days) with corticosteroids or hydroxyurea and a single dose of intrathecal cytarabine.
Exclusion Criteria:
- Patients with Philadelphia chromosome positive ALL, Burkitt's leukemia, mixed lineage/mixed phenotype acute leukemia, and acute undifferentiated leukemia per WHO classification (2016).
- Patients with Down syndrome.
- Patients with Hepatitis B (positive for HBs antigen), and Hepatitis C (HCV antibody) at inclusion
- Participants known to be HIV-positive.
- Known history of non-gallstone-related pancreatitis.
- Known severe hepatic impairment (bilirubin >3 x upper limit of normal [ULN]; transaminases >10 times ULN.
Sites / Locations
- HonorHealth Cancer Transplant Institute
- City of Hope Comprehensive Cancer CenterRecruiting
- Univeristy of CaliforniaRecruiting
- University of Miami Health System - Sylvester Comprehensive Cancer Center
- University of Chicago MedicineRecruiting
- University of Kansas Cancer Center - Richard and Annette Bloch Cancer Care Pavilion
- University of Maryland Greenbaum Cancer CenterRecruiting
- Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsRecruiting
- Dana Farber Cancer InstituteRecruiting
- NYU Langone/Laura and Isaac Perlmutter Cancer CenterRecruiting
- Weill Cornell Medical College
- Memorial Sloan Kettering Cancer CenterRecruiting
- Duke University
- Cleveland ClinicRecruiting
- University of Washington/Seattle Cancer Care AllianceRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Calaspargase pegol (S95015)
Arm Description
Outcomes
Primary Outcome Measures
Adverse Events (AEs) (Part 1)
Including Treatment-emergent adverse events (TEAEs), adverse events of special interests (AESI); laboratory tests; vital signs; serious adverse events (SAEs) and AE. AEs recoded and evaluated throughout the study in accordance with NCI CTCAE criteria 5.0.
Adverse Events (AEs) (Part 2)
Including Treatment-emergent adverse events (TEAEs), adverse events of special interest (AESI); laboratory tests; vital signs; serious adverse events (SAEs) and AEs. AEs recoded and evaluated throughout the study in accordance with NCI CTCAE criteria 5.0.
Plasma Asparaginase Activity (PAA) level (Part 1)
Assessment of PAA in Part 1 is based on population modeling analysis.
Nadir Plasma Asparaginase Activity (NPAA) (Part 2)
NPAA level ≥0.1 U/mL 21 days after the Remission Consolidation Phase Day 43 dose.
Secondary Outcome Measures
Plasma Asparaginase Activity (PAA) level ≥0.1 U/mL at any time during Remission Induction phase and post- Remission Induction phase, respectively (Part 2)
Pharmacodynamics criterion.
Plasma Asparaginase Activity (PAA) level ≥0.025, ≥0.1, ≥0.2, or ≥0.4 U/mL at predefined time points during Remission Induction phase and post- Remission Induction phase, respectively (Part 2)
Pharmacodynamics criterion.
PAA-derived maximum concentration (Cmax) after the Remission Induction Phase Day 4 dose (Part 1 and 2).
PAA-derived Cmax are based on population modeling analysis.
PAA-derived Area Under the PAA-Time Curve From Time 0 to Day 21 (AUC 0-21) after the Remission Induction Phase Day 4 dose (Part 1 and 2).
PAA-derived AUC 0-21 are based on population modeling analysis.
Minimal residual disease (MRD) (Part 1 and 2)
Efficacy criterion.
Complete remission (CR) (Part 1 and 2)
Morphologic complete remission rate (CR), morphologic complete remission rate with incomplete blood count recovery (CRi).
Survival (Part 1 and 2)
1-year EFS (event-free survival), DFS (disease-free survival) and OS (overall survival)
2-year EFS, DFS, OS
3-year EFS, DFS, OS.
Anti-drug (calaspargase pegol) antibody (ADA) development (Part 1 and 2)
Immunogenicity criterion.
Full Information
NCT ID
NCT04817761
First Posted
March 15, 2021
Last Updated
December 13, 2022
Sponsor
Institut de Recherches Internationales Servier
Collaborators
ADIR, a Servier Group company
1. Study Identification
Unique Protocol Identification Number
NCT04817761
Brief Title
Calaspargase Pegol in Adults With ALL
Official Title
A Multi-center, Open-label, Single-arm Phase 2/3 Trial Evaluating the Safety and Pharmacokinetics of Calaspargase Pegol for Treatment of Adults Aged 22 To >65 Years With Newly-diagnosed Philadelphia-negative ALL.
Study Type
Interventional
2. Study Status
Record Verification Date
December 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 7, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
August 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Institut de Recherches Internationales Servier
Collaborators
ADIR, a Servier Group company
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this phase 2/3 study is to confirm the recommended doses and to evaluate the safety and pharmacodynamics of Calaspargase pegol for the treatment of adult patients with Philadelphia-negative Acute Lymphoblastic Leukemia.
Detailed Description
The study will be conducted in 2 parts. Part 1 is a dose confirmation run-in period. Part 2 will enroll the remaining participants at the dose as confirmed in Part 1.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia
Keywords
Acute Lymphoblastic Leukemia, ALL, Ph-negative B-cell and T cell ALL, Philadelphia-negative ALL, Calaspargase Pegol, Asparlas, Adult, Acute Lymphocytic Leukemia, Newly diagnosed ALL, Untreated ALL
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
122 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Calaspargase pegol (S95015)
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Calaspargase pegol (S95015)
Intervention Description
Part 1: S95015 will be administered at dose of 2000 U/m2, 1500 U/m2 or 1000 U/m2 (dose level based on age and BMI) via a 2-hour intravenous infusion at Day 4 (or 5, or 6) of the induction phase, Days 15 and 43 of the consolidation phase, Day 22 of the interim maintenance phase and Days 4 (or 5, or 6) and 43 of the delayed intensification phase. S95015 starting doses for age and BMI groups will be confirmed.
Patients will receive premedication prior to calaspargase pegol administration (acetaminophen, histamine-1 blocker, and corticosteroids to prevent hypersensitivity reaction) and other backbone chemotherapy agents based on the CALGB 10403 protocol treatment regimen.
Part 2: S95015 will be administered at doses as confirmed in part 1.
Primary Outcome Measure Information:
Title
Adverse Events (AEs) (Part 1)
Description
Including Treatment-emergent adverse events (TEAEs), adverse events of special interests (AESI); laboratory tests; vital signs; serious adverse events (SAEs) and AE. AEs recoded and evaluated throughout the study in accordance with NCI CTCAE criteria 5.0.
Time Frame
From signing the ICF through 30 days after the Calaspargase pegol administration at Day 4 (or Day 5 or Day 6) in the Remission Induction phase.
Title
Adverse Events (AEs) (Part 2)
Description
Including Treatment-emergent adverse events (TEAEs), adverse events of special interest (AESI); laboratory tests; vital signs; serious adverse events (SAEs) and AEs. AEs recoded and evaluated throughout the study in accordance with NCI CTCAE criteria 5.0.
Time Frame
From signing the ICF through 30 days after the last dose of the study drug in Delayed Intensification phase.
Title
Plasma Asparaginase Activity (PAA) level (Part 1)
Description
Assessment of PAA in Part 1 is based on population modeling analysis.
Time Frame
Days 4, 5, 6 (Remission Induction phase) for PAA samples. Days 11, 18, 25 (Remission Induction phase) for TDM samples.
Title
Nadir Plasma Asparaginase Activity (NPAA) (Part 2)
Description
NPAA level ≥0.1 U/mL 21 days after the Remission Consolidation Phase Day 43 dose.
Time Frame
Day 64 (Remission Consolidation Phase).
Secondary Outcome Measure Information:
Title
Plasma Asparaginase Activity (PAA) level ≥0.1 U/mL at any time during Remission Induction phase and post- Remission Induction phase, respectively (Part 2)
Description
Pharmacodynamics criterion.
Time Frame
Days 4-5-6 & 11-18-25 (Remission Induction); Days 15-16-43-44 & 22-29-36-50-57-64 (Consolidation); Days 22-23 & 29-36-43 (Interim Maintenance); Days 4-5,43-44 & 11-18-25-50-57-64 (Delayed Intensification) for PAA & TDM samples respectively.
Title
Plasma Asparaginase Activity (PAA) level ≥0.025, ≥0.1, ≥0.2, or ≥0.4 U/mL at predefined time points during Remission Induction phase and post- Remission Induction phase, respectively (Part 2)
Description
Pharmacodynamics criterion.
Time Frame
Days 4-5-6 & 11-18-25 (Remission Induction); Days 15-16-43-44 & 22-29-36-50-57-64 (Consolidation); Days 22-23 & 29-36-43 (Interim Maintenance); Days 4-5-43-44 & 11-18-25-50-57-64 (Delayed Intensification) for PAA & TDM samples respectively.
Title
PAA-derived maximum concentration (Cmax) after the Remission Induction Phase Day 4 dose (Part 1 and 2).
Description
PAA-derived Cmax are based on population modeling analysis.
Time Frame
Days 4, 5, 6 & 11, 18, 25 (Remission Induction); for PAA & TDM samples respectively.
Title
PAA-derived Area Under the PAA-Time Curve From Time 0 to Day 21 (AUC 0-21) after the Remission Induction Phase Day 4 dose (Part 1 and 2).
Description
PAA-derived AUC 0-21 are based on population modeling analysis.
Time Frame
Days 4, 5, 6 & 11, 18, 25 (Remission Induction); for PAA & TDM samples respectively.
Title
Minimal residual disease (MRD) (Part 1 and 2)
Description
Efficacy criterion.
Time Frame
End of remission induction phase (Day 29).
Title
Complete remission (CR) (Part 1 and 2)
Description
Morphologic complete remission rate (CR), morphologic complete remission rate with incomplete blood count recovery (CRi).
Time Frame
Day 29 remission induction therapy
Title
Survival (Part 1 and 2)
Description
1-year EFS (event-free survival), DFS (disease-free survival) and OS (overall survival)
2-year EFS, DFS, OS
3-year EFS, DFS, OS.
Time Frame
Through study completion an average of 3 months.
Title
Anti-drug (calaspargase pegol) antibody (ADA) development (Part 1 and 2)
Description
Immunogenicity criterion.
Time Frame
D4, D18, D29 (Remission Induction Phase), D15, D43 (Remission Consolidation Phase), D22 (Interim Maintenance Phase), D4, D43 (Delayed Intensification Phase), Day 365 (±7) after the first dose, Day 30 after the last dose if discontinuation.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
22 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Aged ≥22 years with newly-diagnosed and cytologically confirmed and documented Philadelphia-negative B-cell or T-cell ALL by World Health Organization (WHO) classification (2016).
Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2.
No prior therapy for ALL such as chemotherapy and radiation therapy before signing the informed consent except for limited treatment (≤7 days) with corticosteroids or hydroxyurea and a single dose of intrathecal cytarabine.
Exclusion Criteria:
Patients with Philadelphia chromosome positive ALL, Burkitt's leukemia, mixed lineage/mixed phenotype acute leukemia, and acute undifferentiated leukemia per WHO classification (2016).
Patients with Down syndrome.
Patients with Hepatitis B (positive for HBs antigen), and Hepatitis C (HCV antibody) at inclusion
Participants known to be HIV-positive.
Known history of non-gallstone-related pancreatitis.
Known severe hepatic impairment (bilirubin >3 x upper limit of normal [ULN]; transaminases >10 times ULN.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Institut de Recherches Internationales Servier, Clinical Studies Department
Phone
+33 1 55 72 43 66
Email
scientificinformation@servier.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daniel J. DeAngelo, MD, PhD
Organizational Affiliation
Dana-Farber Cancer Institute, Boston, MA
Official's Role
Principal Investigator
Facility Information:
Facility Name
HonorHealth Cancer Transplant Institute
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85258
Country
United States
Individual Site Status
Withdrawn
Facility Name
City of Hope Comprehensive Cancer Center
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
626-218-3279
Facility Name
Univeristy of California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Miami Health System - Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of Chicago Medicine
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
626-218-3279
Facility Name
University of Kansas Cancer Center - Richard and Annette Bloch Cancer Care Pavilion
City
Westwood
State/Province
Kansas
ZIP/Postal Code
66205
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of Maryland Greenbaum Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
410-328-6841
Facility Name
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21287
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
410-614-9106
Phone
+1 410 614 72
Facility Name
Dana Farber Cancer Institute
City
Weymouth
State/Province
Massachusetts
ZIP/Postal Code
02190
Country
United States
Individual Site Status
Recruiting
Facility Name
NYU Langone/Laura and Isaac Perlmutter Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
646-501-4818
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Individual Site Status
Withdrawn
Facility Name
Memorial Sloan Kettering Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10065
Country
United States
Individual Site Status
Recruiting
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Individual Site Status
Withdrawn
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Washington/Seattle Cancer Care Alliance
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
Phone
206-606-1202
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Qualified scientific and medical researchers can request access to anonymized patient-level and study-level clinical trial data.
Access can be requested for all interventional clinical studies:
used for Marketing Authorization (MA) of medicines and new indications approved after 1 January 2014 in the European Economic Area (EEA) or the United States (US).
where Servier is the Marketing Authorization Holder (MAH). The date of the first MA of the new medicine (or the new indication) in one of the EEA Member States will be considered for this scope.
In addition, access can be requested for all interventional clinical studies in patients:
sponsored by Servier
with a first patient enrolled as of 1 January 2004 onwards
for New Chemical Entity or New Biological Entity (new pharmaceutical form excluded) for which development has been terminated before any Marketing authorization (MA) approval.
IPD Sharing Time Frame
After Marketing Authorisation in EEA or US if the study is used for the approval.
IPD Sharing Access Criteria
Researchers should register on Servier Data Portal and fill in the research proposal form. This form in four parts should be fully documented. The Research Proposal Form will not be reviewed until all mandatory fields are completed.
IPD Sharing URL
https://clinicaltrials.servier.com/
Links:
URL
https://clinicaltrials.servier.com/
Description
Find Results on Servier Clinical Trial Data website
Available IPD and Supporting Information:
Available IPD/Information Type
Individual Participant Data Set
Available IPD/Information URL
https://clinicaltrials.servier.com/
Available IPD/Information Type
Study Protocol
Available IPD/Information URL
https://clinicaltrials.servier.com/
Available IPD/Information Type
Statistical Analysis Plan
Available IPD/Information URL
https://clinicaltrials.servier.com/
Available IPD/Information Type
Informed Consent Form
Available IPD/Information URL
https://clinicaltrials.servier.com/
Available IPD/Information Type
Clinical Study Report
Available IPD/Information URL
https://clinicaltrials.servier.com/
Available IPD/Information Type
Study-level clinical trial data
Available IPD/Information URL
https://clinicaltrials.servier.com/
Learn more about this trial
Calaspargase Pegol in Adults With ALL
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