SPARK-ALL: Calaspargase Pegol in Adults With ALL
- Conditions
- Acute Lymphoblastic Leukemia
- Interventions
- Drug: Calaspargase pegol (S95015)
- Registration Number
- NCT04817761
- Lead Sponsor
- Institut de Recherches Internationales Servier
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 122
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Calaspargase pegol (S95015) Calaspargase pegol (S95015) -
- Primary Outcome Measures
Name Time Method Adverse Events (AEs) (Part 2) 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.
Adverse Events (AEs) (Part 1) 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.
Plasma Asparaginase Activity (PAA) level (Part 1) 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.
Nadir Plasma Asparaginase Activity (NPAA) (Part 2) Day 64 (Remission Consolidation Phase). NPAA level ≥0.1 U/mL 21 days after the Remission Consolidation Phase Day 43 dose.
- Secondary Outcome Measures
Name Time Method Minimal residual disease (MRD) (Part 1 and 2) End of remission induction phase (Day 29). Efficacy criterion.
Complete remission (CR) (Part 1 and 2) Day 29 remission induction therapy Morphologic complete remission rate (CR), morphologic complete remission rate with incomplete blood count recovery (CRi).
Survival (Part 1 and 2) 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.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). 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.
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) 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.
PAA-derived maximum concentration (Cmax) after the Remission Induction Phase Day 4 dose (Part 1 and 2). Days 4, 5, 6 & 11, 18, 25 (Remission Induction); for PAA & TDM samples respectively. PAA-derived Cmax are based on population modeling analysis.
Plasma Asparaginase Activity (PAA) level ≥0.1 U/mL at any time during Remission Induction phase and post- Remission Induction phase, respectively (Part 2) 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.
Anti-drug (calaspargase pegol) antibody (ADA) development (Part 1 and 2) 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.
Trial Locations
- Locations (22)
West Virginia University Cancer Institute
🇺🇸Morgantown, West Virginia, United States
HonorHealth Cancer Transplant Institute
🇺🇸Scottsdale, Arizona, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Univeristy of California
🇺🇸Los Angeles, California, United States
University of California Irvine Health (UCI Health)
🇺🇸Orange, California, United States
University of Miami Health System - Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
University of Chicago Medicine
🇺🇸Chicago, Illinois, United States
University of Kansas Cancer Center - Richard and Annette Bloch Cancer Care Pavilion
🇺🇸Westwood, Kansas, United States
University of Maryland Greenbaum Cancer Center
🇺🇸Baltimore, Maryland, United States
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
🇺🇸Baltimore, Maryland, United States
Dana Farber Cancer Institute
🇺🇸Weymouth, Massachusetts, United States
Northwell Health Cancer Institute
🇺🇸Lake Success, New York, United States
NYU Langone/Laura and Isaac Perlmutter Cancer Center
🇺🇸New York, New York, United States
Weill Cornell Medical College
🇺🇸New York, New York, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
Duke University
🇺🇸Durham, North Carolina, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
Oregon Health & Science University (OHSU)
🇺🇸Portland, Oregon, United States
Jefferson Health
🇺🇸Philadelphia, Pennsylvania, United States
Baptist Clinical Research Institute
🇺🇸Memphis, Tennessee, United States
Intermountain Healthcare (IHC)
🇺🇸Salt Lake City, Utah, United States
University of Washington/Seattle Cancer Care Alliance/Fred Hutch
🇺🇸Seattle, Washington, United States