SPARK-ALL: Calaspargase Pegol in Adults With ALL

Phase 3Active Not RecruitingNCT04817761

Institut de Recherches Internationales Servier122 enrolled

Overview

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.

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

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

122

Conditions

Acute Lymphoblastic Leukemia

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.

Eligibility

Sex: ALLMin age: 22 YearsMax age: 55 Years

Medical Language ↔ Plain English

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.

Locations (19)

City of Hope Comprehensive Cancer Center

Duarte, California, United States

Outcomes

Primary Outcomes

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.

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.

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.

Time frame: 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.

Time frame: 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.

Time frame: Day 64 (Remission Consolidation Phase).

Secondary Outcomes

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.

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.

Data from ClinicalTrials.gov

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