SPARK-ALL: Calaspargase Pegol in Adults With ALL

NCT04817761 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: CL2-95015-001
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 21

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.

Conditions

Acute Lymphoblastic Leukemia

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

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (8)

• 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.

• 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.

• 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 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.

• Minimal residual disease (MRD) (Part 1 and 2)

  End of remission induction phase (Day 29).

Study Arms (1)

Calaspargase pegol (S95015)

EXPERIMENTAL

Drug: Calaspargase pegol (S95015)

Interventions

Calaspargase pegol (S95015) DRUG

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.

Calaspargase pegol (S95015)

Eligibility Criteria

• Age: 22 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Institut de Recherches Internationales Servier: lead
• ADIR, a Servier Group company: collaborator

Study Sites (21)

HonorHealth Cancer Transplant Institute

Scottsdale, Arizona, 85258, United States

Location

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Univeristy of California

Los Angeles, California, 90095, United States

Location

University of California Irvine Health (UCI Health)

Orange, California, 92868, United States

Location

University of Miami Health System - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136, United States

Location

University of Chicago Medicine

Chicago, Illinois, 60637, United States

Location

University of Kansas Cancer Center - Richard and Annette Bloch Cancer Care Pavilion

Westwood, Kansas, 66205, United States

Location

University of Maryland Greenbaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

Dana Farber Cancer Institute

Weymouth, Massachusetts, 02190, United States

Location

Northwell Health Cancer Institute

Lake Success, New York, 11042, United States

Location

NYU Langone/Laura and Isaac Perlmutter Cancer Center

New York, New York, 10016, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Duke University

Durham, North Carolina, 27705, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health & Science University (OHSU)

Portland, Oregon, 97239, United States

Location

Jefferson Health

Philadelphia, Pennsylvania, 19107, United States

Location

Baptist Clinical Research Institute

Memphis, Tennessee, 38120, United States

Location

Intermountain Healthcare (IHC)

Salt Lake City, Utah, 84143, United States

Location

University of Washington/Seattle Cancer Care Alliance/Fred Hutch

Seattle, Washington, 98109, United States

Location

West Virginia University Cancer Institute

Morgantown, West Virginia, 26506, United States

Location

Related Publications (2)

• 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

  BACKGROUND

• 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.

  PMID: 41074700 DERIVED

Related Links

• Find Results on Servier Clinical Trial Data website

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Interventions

calaspargase pegol

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Daniel J. DeAngelo, MD, PhD

  Dana-Farber Cancer Institute, Boston, MA

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 15, 2021
• First Posted: March 26, 2021
• Study Start: July 7, 2021
• Primary Completion: March 21, 2025
• Study Completion: March 21, 2025
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (21)