Clinical trial NCT04817761: SPARK-ALL: Calaspargase Pegol in Adults with ALL
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.
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
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
Lead sponsor: Servier
Sponsor class: INDUSTRY
Collaborators: name: ADIR, a Servier Group company
First posted: 2021-03-26
Enrollment: 122
Sex: ALL
Minimum age (years): 22
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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 or recommended in Part 1.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse Events (AEs) (Part 1)
timeFrame: 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.
measure: Adverse Events (AEs) (Part 2)
timeFrame: From signing the ICF through 30 days after the last dose of the study drug in Delayed Intensification phase.
measure: Plasma Asparaginase Activity (PAA) level (Part 1)
timeFrame: Days 4, 5, 6 (Remission Induction phase) for PAA samples. Days 11, 18, 25 (Remission Induction phase) for TDM samples.
measure: Nadir Plasma Asparaginase Activity (NPAA) (Part 2)
timeFrame: Day 64 (Remission Consolidation Phase).
Secondary outcomes:
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)
timeFrame: 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.
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)
timeFrame: 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.
measure: PAA-derived maximum concentration (Cmax) after the Remission Induction Phase Day 4 dose (Part 1 and 2).
timeFrame: Days 4, 5, 6 & 11, 18, 25 (Remission Induction); for PAA & TDM samples respectively.
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).
timeFrame: Days 4, 5, 6 & 11, 18, 25 (Remission Induction); for PAA & TDM samples respectively.
measure: Minimal residual disease (MRD) (Part 1 and 2)
timeFrame: End of remission induction phase (Day 29).
measure: Complete remission (CR) (Part 1 and 2)
timeFrame: Day 29 remission induction therapy
measure: Survival (Part 1 and 2)
timeFrame: Through study completion an average of 3 months.
measure: Anti-drug (calaspargase pegol) antibody (ADA) development (Part 1 and 2)
timeFrame: 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.
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: Los Angeles
country: United States
facility: Univeristy of California
state: California
city: Orange
country: United States
facility: University of California Irvine Health (UCI Health)
state: California
city: Miami
country: United States
facility: University of Miami Health System - Sylvester Comprehensive Cancer Center
state: Florida
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Westwood
country: United States
facility: University of Kansas Cancer Center - Richard and Annette Bloch Cancer Care Pavilion
state: Kansas
city: Baltimore
country: United States
facility: University of Maryland Greenbaum Cancer Center
state: Maryland
city: Baltimore
country: United States
facility: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
state: Maryland
city: Weymouth
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Lake Success
country: United States
facility: Northwell Health Cancer Institute
state: New York
city: New York
country: United States
facility: NYU Langone/Laura and Isaac Perlmutter Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University (OHSU)
state: Oregon
city: Philadelphia
country: United States
facility: Jefferson Health
state: Pennsylvania
city: Memphis
country: United States
facility: Baptist Clinical Research Institute
state: Tennessee
city: Salt Lake City
country: United States
facility: Intermountain Healthcare (IHC)
state: Utah
city: Seattle
country: United States
facility: University of Washington/Seattle Cancer Care Alliance/Fred Hutch
state: Washington
city: Morgantown
country: United States
facility: West Virginia University Cancer Institute
state: West Virginia
Study officials:
affiliation: Dana-Farber Cancer Institute, Boston, MA
name: Daniel J. DeAngelo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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