Description:
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.
Title
- 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.
Clinical Trial IDs
- ORG STUDY ID:
CL2-95015-001
- NCT ID:
NCT04817761
Conditions
- Acute Lymphoblastic Leukemia
Interventions
| Drug | Synonyms | Arms |
|---|
| Calaspargase pegol (S95015) | | Calaspargase pegol (S95015) |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Calaspargase pegol (S95015) | Experimental | | - Calaspargase pegol (S95015)
|
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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 22 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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. |
| Safety Issue: | |
| 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. |
Secondary Outcome Measures
| Measure: | 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. |
| Safety Issue: | |
| Description: | Pharmacodynamics criterion. |
| Measure: | 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. |
| Safety Issue: | |
| Description: | Pharmacodynamics criterion. |
| Measure: | 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. |
| Safety Issue: | |
| Description: | PAA-derived Cmax are based on population modeling analysis. |
| Measure: | 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. |
| Safety Issue: | |
| Description: | PAA-derived AUC 0-21 are based on population modeling analysis. |
| Measure: | Minimal residual disease (MRD) (Part 1 and 2) |
| Time Frame: | End of remission induction phase (Day 29). |
| Safety Issue: | |
| Description: | Efficacy criterion. |
| Measure: | Complete remission (CR) (Part 1 and 2) |
| Time Frame: | Day 29 remission induction therapy |
| Safety Issue: | |
| Description: | Morphologic complete remission rate (CR), morphologic complete remission rate with incomplete blood count recovery (CRi). |
| Measure: | Survival (Part 1 and 2) |
| Time Frame: | Through study completion an average of 3 months. |
| Safety Issue: | |
| 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. |
| Measure: | 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. |
| Safety Issue: | |
| Description: | Immunogenicity criterion. |
Details
| Phase: | Phase 2/Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Not yet recruiting |
| Lead Sponsor: | Institut de Recherches Internationales Servier |
Trial 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
Last Updated
March 26, 2021
