This is the classic website, which will be retired eventually. Please visit the modernized ClinicalTrials.gov instead.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Calaspargase Pegol in Adults With ALL

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04817761
Recruitment Status : Recruiting
First Posted : March 26, 2021
Last Update Posted : February 5, 2024
Sponsor:
Collaborator:
ADIR, a Servier Group company
Information provided by (Responsible Party):
Servier ( Institut de Recherches Internationales Servier )

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Drug: Calaspargase pegol (S95015) Phase 2 Phase 3

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.
Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 122 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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.
Actual Study Start Date : July 7, 2021
Actual Primary Completion Date : December 30, 2023
Estimated Study Completion Date : February 2027

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Calaspargase pegol (S95015) Drug: Calaspargase pegol (S95015)

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: Patients aged 22 to 39 years + BMI ≤ 35 kg/m2 will be treated with S95015 1750 U/m2.

Patients aged 40 to < 55 years + BMI ≤ 35 kg/m2 will be treated with S95015 1500 U/m2, unchanged from Part 1. Patients 55 years or older or those with a BMI greater than 35 kg/m2 will no longer be enrolled into Part 2.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  1. Adverse Events (AEs) (Part 1) [ 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. ]
    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.

  2. Adverse Events (AEs) (Part 2) [ Time Frame: From signing the ICF through 30 days after the last dose of the study drug in Delayed Intensification phase. ]
    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.

  3. Plasma Asparaginase Activity (PAA) level (Part 1) [ Time Frame: Days 4, 5, 6 (Remission Induction phase) for PAA samples. Days 11, 18, 25 (Remission Induction phase) for TDM samples. ]
    Assessment of PAA in Part 1 is based on population modeling analysis.

  4. Nadir Plasma Asparaginase Activity (NPAA) (Part 2) [ Time Frame: Day 64 (Remission Consolidation Phase). ]
    NPAA level ≥0.1 U/mL 21 days after the Remission Consolidation Phase Day 43 dose.


Secondary Outcome Measures :
  1. Plasma Asparaginase Activity (PAA) level ≥0.1 U/mL at any time during Remission Induction phase and post- Remission Induction phase, respectively (Part 2) [ 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. ]
    Pharmacodynamics criterion.

  2. 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) [ 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. ]
    Pharmacodynamics criterion.

  3. PAA-derived maximum concentration (Cmax) after the Remission Induction Phase Day 4 dose (Part 1 and 2). [ Time Frame: Days 4, 5, 6 & 11, 18, 25 (Remission Induction); for PAA & TDM samples respectively. ]
    PAA-derived Cmax are based on population modeling analysis.

  4. 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). [ Time Frame: Days 4, 5, 6 & 11, 18, 25 (Remission Induction); for PAA & TDM samples respectively. ]
    PAA-derived AUC 0-21 are based on population modeling analysis.

  5. Minimal residual disease (MRD) (Part 1 and 2) [ Time Frame: End of remission induction phase (Day 29). ]
    Efficacy criterion.

  6. Complete remission (CR) (Part 1 and 2) [ Time Frame: Day 29 remission induction therapy ]
    Morphologic complete remission rate (CR), morphologic complete remission rate with incomplete blood count recovery (CRi).

  7. Survival (Part 1 and 2) [ Time Frame: Through study completion an average of 3 months. ]
    • 1-year EFS (event-free survival), DFS (disease-free survival) and OS (overall survival)
    • 2-year EFS, DFS, OS
    • 3-year EFS, DFS, OS.

  8. Anti-drug (calaspargase pegol) antibody (ADA) development (Part 1 and 2) [ 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. ]
    Immunogenicity criterion.


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   22 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged ≥22 and <55 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.
  • Pre-existing history of hepatic veno-occlusive disease (VOD).
  • Age ≥ 55 years.
  • BMI > 35 kg/m2.
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04817761


Contacts
Layout table for location contacts
Contact: Institut de Recherches Internationales Servier, Clinical Studies Department +33 1 55 72 43 66 scientificinformation@servier.com

Locations
Show Show 17 study locations
Sponsors and Collaborators
Institut de Recherches Internationales Servier
ADIR, a Servier Group company
Investigators
Layout table for investigator information
Principal Investigator: Daniel J. DeAngelo, MD, PhD Dana-Farber Cancer Institute, Boston, MA
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Study Data/Documents: Individual Participant Data Set  This link exits the ClinicalTrials.gov site
Study Protocol  This link exits the ClinicalTrials.gov site
Statistical Analysis Plan  This link exits the ClinicalTrials.gov site
Informed Consent Form  This link exits the ClinicalTrials.gov site
Clinical Study Report  This link exits the ClinicalTrials.gov site
Study-level clinical trial data  This link exits the ClinicalTrials.gov site

Layout table for additonal information
Responsible Party: Institut de Recherches Internationales Servier
ClinicalTrials.gov Identifier: NCT04817761    
Other Study ID Numbers: CL2-95015-001
First Posted: March 26, 2021    Key Record Dates
Last Update Posted: February 5, 2024
Last Verified: February 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: After Marketing Authorisation in EEA or US if the study is used for the approval.
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.
URL: https://clinicaltrials.servier.com/

Layout table for additional information
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
Keywords provided by Servier ( Institut de Recherches Internationales Servier ):
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
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Leukemia, Lymphoid
Neoplasms by Histologic Type
Neoplasms
 Hematologic Diseases
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases