SPARK-ALL: Calaspargase Pegol in Adults With ALL

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.

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.

Study Overview

• Status: Terminated
• Conditions: Acute Lymphoblastic Leukemia
• Intervention / Treatment: Drug: Calaspargase pegol (S95015)

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 or recommended in Part 1.

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth Cancer Transplant Institute
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • Los Angeles, California, United States, 90095
      • Univeristy of California
    • Orange, California, United States, 92868
      • University of California Irvine Health (UCI Health)
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami Health System - Sylvester Comprehensive Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medicine
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Cancer Center - Richard and Annette Bloch Cancer Care Pavilion
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenbaum Cancer Center
  • Massachusetts
    • Weymouth, Massachusetts, United States, 02190
      • Dana Farber Cancer Institute
  • New York
    • Lake Success, New York, United States, 11042
      • Northwell Health Cancer Institute
    • New York, New York, United States, 10065
      • Memorial Sloan Kettering Cancer Center
    • New York, New York, United States, 10016
      • NYU Langone/Laura and Isaac Perlmutter Cancer Center
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Duke University
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Science University (OHSU)
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Jefferson Health
  • Tennessee
    • Memphis, Tennessee, United States, 38120
      • Baptist Clinical Research Institute
  • Utah
    • Salt Lake City, Utah, United States, 84143
      • Intermountain Healthcare (IHC)
  • Washington
    • Seattle, Washington, United States, 98109
      • University of Washington/Seattle Cancer Care Alliance/Fred Hutch
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • West Virginia University Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 22 years and older (Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.
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.
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.
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.
Minimal residual disease (MRD) (Part 1 and 2)	Efficacy criterion.	End of remission induction phase (Day 29).
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
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.
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.

Collaborators and Investigators

• Sponsor: Institut de Recherches Internationales Servier
• Collaborators: ADIR, a Servier Group company
• Investigators: Principal Investigator: Daniel J. DeAngelo, MD, PhD, Dana-Farber Cancer Institute, Boston, MA

Publications and helpful links

General Publications

• Stock W, Park JH, Emadi A, Abdul-Hay M, Cassaday RD, Pullarkat VA, Webster J, Pandya SS, Mogul MJ, Shvenke Y, Zhu JJ, Tessier A, DeAngelo DJ. Safety and Pharmacokinetics of Calaspargase Pegol in Adults with Newly Diagnosed Philadelphia-Negative ALL: A Phase 2/3 Study. Blood. 2021 Nov 23;138(Supplement 1):4406. doi: https://doi.org/10.1182/blood-2021-149463
• Aldoss I, Ali A, Cassaday RD, Curran EK, Luskin MR, Maese LD, Orgel E, Douer D. Optimizing Asparaginase Treatment for Adolescent and Young Adult (AYA) Patients With Acute Lymphoblastic Leukemia: US Consensus Panel Recommendations. Am J Hematol. 2026 Jan;101(1):41-55. doi: 10.1002/ajh.70103. Epub 2025 Oct 11.

Helpful Links

• Find Results on Servier Clinical Trial Data website

Study record dates

Study Major Dates

• Study Start (Actual): July 7, 2021
• Primary Completion (Actual): March 21, 2025
• Study Completion (Actual): March 21, 2025

Study Registration Dates

• First Submitted: March 15, 2021
• First Submitted That Met QC Criteria: March 23, 2021
• First Posted (Actual): March 26, 2021

Study Record Updates

• Last Update Posted (Actual): February 18, 2026
• Last Update Submitted That Met QC Criteria: February 16, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: ALL; Adult; Acute Lymphoblastic Leukemia; Ph-negative B-cell and T cell ALL; Philadelphia-negative ALL; Calaspargase Pegol; Asparlas; Acute Lymphocytic Leukemia; Newly diagnosed ALL; Untreated ALL
• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Leukemia, Lymphoid; Leukemia; Hemic and Lymphatic Diseases; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; calaspargase pegol
• Other Study ID Numbers: CL2-95015-001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD 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 Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Study Data/Documents

1. Individual Participant Data Set
2. Study Protocol
3. Statistical Analysis Plan
4. Informed Consent Form
5. Clinical Study Report
6. Study-level clinical trial data

Drug and device information, study documents

• 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