SPARK-ALL: Calaspargase Pegol in Adults With ALL

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

SPARK-ALL: 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 Details — Status: Recruiting

Administrative data

• NCT number: NCT04817761
• Other study ID #: CL2-95015-001
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: July 7, 2021
• Est. completion date: February 2027

Study information

• Verified date: June 2024
• Source: Servier
• Contact: Institut de Recherches Internationales Servier, Clinical Studies
• Phone: +33 1 55 72 43 66
• Email: scientificinformation[@]servier.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 122
• Est. completion date: February 2027
• Est. primary completion date: December 30, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 22 Years to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

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.

Locations

Country	Name	City	State
United States	Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins	Baltimore	Maryland
United States	University of Maryland Greenbaum Cancer Center	Baltimore	Maryland
United States	University of Chicago Medicine	Chicago	Illinois
United States	Cleveland Clinic	Cleveland	Ohio
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	Duke University	Durham	North Carolina
United States	Univeristy of California	Los Angeles	California
United States	Baptist Clinical Research Institute	Memphis	Tennessee
United States	University of Miami Health System - Sylvester Comprehensive Cancer Center	Miami	Florida
United States	Memorial Sloan Kettering Cancer Center	New York	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	University of California Irvine Health (UCI Health)	Orange	California
United States	HonorHealth Cancer Transplant Institute	Scottsdale	Arizona
United States	University of Washington/Seattle Cancer Care Alliance/Fred Hutch	Seattle	Washington
United States	University of Kansas Cancer Center - Richard and Annette Bloch Cancer Care Pavilion	Westwood	Kansas
United States	Dana Farber Cancer Institute	Weymouth	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Institut de Recherches Internationales Servier	ADIR, a Servier Group company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	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.
Primary	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.	From signing the ICF through 30 days after the last dose of the study drug in Delayed Intensification phase.
Primary	Plasma Asparaginase Activity (PAA) level (Part 1)	Assessment of PAA in Part 1 is based on population modeling analysis.	Days 4, 5, 6 (Remission Induction phase) for PAA samples. Days 11, 18, 25 (Remission Induction phase) for TDM samples.
Primary	Nadir Plasma Asparaginase Activity (NPAA) (Part 2)	NPAA level =0.1 U/mL 21 days after the Remission Consolidation Phase Day 43 dose.	Day 64 (Remission Consolidation Phase).
Secondary	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.	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.
Secondary	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.	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.
Secondary	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.	Days 4, 5, 6 & 11, 18, 25 (Remission Induction); for PAA & TDM samples respectively.
Secondary	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.	Days 4, 5, 6 & 11, 18, 25 (Remission Induction); for PAA & TDM samples respectively.
Secondary	Minimal residual disease (MRD) (Part 1 and 2)	Efficacy criterion.	End of remission induction phase (Day 29).
Secondary	Complete remission (CR) (Part 1 and 2)	Morphologic complete remission rate (CR), morphologic complete remission rate with incomplete blood count recovery (CRi).	Day 29 remission induction therapy
Secondary	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.	Through study completion an average of 3 months.
Secondary	Anti-drug (calaspargase pegol) antibody (ADA) development (Part 1 and 2)	Immunogenicity criterion.	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.

External Links

•   Find Results on Servier Clinical Trial Data website