A Clinical Study of SHP674 (Pegaspargase) in Participants With Newly Diagnosed, Untreated Acute Lymphoblastic Leukemia

• ClinicalTrials.gov Identifier: NCT04067518
• Recruitment Status: Completed
• First Posted: August 26, 2019
• Results First Posted: June 10, 2022
• Last Update Posted: August 31, 2022
• Sponsor: Institut de Recherches Internationales Servier
• Collaborators: Kyowa Kirin Co., Ltd.; ADIR, a Servier Group company
• Information provided by (Responsible Party): Servier ( Institut de Recherches Internationales Servier )

Study Description

Brief Summary:

The objectives of the study are to assess the safety and tolerability of a single dose of SHP674 in Japanese participants (dose confirmation) in the tolerability assessment period of Part 1 and to assess the safety, pharmacokinetics and efficacy of SHP674 dose in Part 2 (found to be tolerated in Part 1) in the treatment of newly diagnosed untreated acute lymphoblastic leukemia (ALL) in Japanese participants.

Condition or disease	Intervention/treatment	Phase
Acute Lymphoblastic Leukemia	Biological: SHP674	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 28 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Intervention Model Description: The intervention study model is sequential in results section of record.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 2 Clinical Study of SHP674 in Patients With Newly Diagnosed, Untreated Acute Lymphoblastic Leukemia
• Actual Study Start Date: October 17, 2019
• Actual Primary Completion Date: February 12, 2021
• Actual Study Completion Date: February 4, 2022

Arms and Interventions

Arm

Intervention/treatment

Experimental: SHP674; Part 1: Participants with ALL who were stratified into the standard risk (SR) or intermediate risk (IR) groups received total 3 doses of SHP674 in the 36-week treatment period and who were stratified into the high risk (HR) group received total 8 doses of SHP674 in the 45-week treatment period. Part 2: Participants with ALL who were stratified into the SR or IR groups received total 3 doses of SHP674 in the 41-week treatment period and who were stratified into the HR group received total 8 doses of SHP674 in the 45-week treatment period.

Biological: SHP674; SHP674: powder for solution for injection, IV (administered by 1 to 2 hours of drip infusion), dose determination : if BSA ≥0.6 m^2: 2500 IU/m^2 every 14 days if BSA <0.6 m^2: 82.5 IU/kg every 14 days; Other Name: Pegaspargase

Outcome Measures

Primary Outcome Measures :

1. Part 1: Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) and SHP-674-Related TEAEs During the Tolerability Assessment Period [ Time Frame: Enrollment up to 5 weeks ]
   An adverse event (AE) is defined as any untoward medical occurrence in a participant after signing informed consent. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease, whether or not it is related to the investigational product. TEAE is defined as any untoward medical occurrence in a participant who received an investigational product which occurs during the period from Day 1 of the pre-treatment phase to 30 (+7) days after the last dose of investigational product, or until the start of a new therapy, whichever occurs first. A related adverse event signifies that there is a reasonable causal relationship between study treatment and an AE.
2. Part 2: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 International Units Per Milliliter (IU/mL) 14 Days (336 Hours) After the First Dose of SHP674 [ Time Frame: 14 days after the first dose of SHP674 ]

Secondary Outcome Measures :

1. Incidence and Nature of TEAEs and Drug-related TEAEs [ Time Frame: Up to 1 year ]
   Data is not available as participants response is still ongoing at the time of primary analysis.
2. Parts 1 and 2: Percentage of Participants With Anti-Drug (SHP674) Antibody (ADA) and Anti-Polyethylene Glycol (PEG) Antibody [ Time Frame: Part 1: Predose and 25 days post dose; Part 2: Predose and 25 days post dose ]
3. Part 1: Percentage of Participants Who Achieved a Plasma Asparaginase Activity of ≥0.1 IU/mL 14 Days (336 Hours) After the First Dose of SHP674 [ Time Frame: 14 days after the first dose of SHP674 ]
4. Part 2: Percentage of Participants With Plasma Asparaginase Activity of ≥0.1 IU/mL or <0.1 IU/mL [ Time Frame: Day 1 (pre-dose, 5 min, 4 hours, 24 hours post dose), Days 2, 4, 11, 14, 18, 25 post dose ]
5. Survival Rate at 1 Year After the Start of Study Treatment [ Time Frame: 1 year after the start of study treatment ]
   Data is not available as survival follow up of participants is still ongoing at the time of primary analysis.
6. Event-free Survival Rate at 1 Year After the Start of Study Treatment [ Time Frame: 1 year after the start of study treatment ]
   Data is not available as survival follow up of participants is still ongoing at the time of primary analysis.

Eligibility Criteria

• Ages Eligible for Study: 1 Year to 21 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Age 1 to ≤21 years at the time of informed consent;
• Eastern Cooperative Oncology Group performance status (ECOG PS) 0 to 2;
• Newly diagnosed, untreated precursor B-cell ALL
• No prior therapy for malignant tumor such as chemotherapy and radiation therapy before signing the informed consent;
• Life expectancy of at least 6 months from the date of enrollment;

Exclusion Criteria:

• Mature B-cell ALL ; Philadelphia chromosome-positive (Ph+) or BCR-ABL1-positive ALL
• Preexisting known coagulopathy ;
• History of pancreatitis;
• Continuous use of corticosteroids;
• Prior treatment or possible prior treatment with an L-asparaginase preparation;
• History of sensitivity to polyethylene glycol (PEG) or PEG-based drugs;
• Pregnant

Contacts and Locations

Locations

Japan

Kagoshima University Hospital Department of Pediatrics

Kagoshima, Japan

Kobe Children's Hospital Department of Hematology/Oncology

Kobe, Japan

Nagoya Medical Center Department of Pediatrics

Nagoya, Japan

Niigata Cancer Center Hospital

Niigata, Japan

Saitama Children's Medical Center Department of Hematology/Oncology

Saitama, Japan

Sapporo Hokuyu Hospital Department of Pediatrics and Adolescent Medicine

Sapporo, Japan

National Cancer Center Hospital Department of Pediatric Oncology

Tokyo, Japan

St. Luke's International Hospital Department of Pediatrics

Tokyo, Japan

Sponsors and Collaborators

Institut de Recherches Internationales Servier

Kyowa Kirin Co., Ltd.

ADIR, a Servier Group company

Investigators

• Principal Investigator: Chitose Ogawa, MD; National Cancer Center Hospital, Tokyo JAPAN

  Study Documents (Full-Text)

Documents provided by Servier ( Institut de Recherches Internationales Servier ):

Study Protocol  [PDF] January 22, 2021

Statistical Analysis Plan  [PDF] April 5, 2021

More Information

Additional Information:

Find Results on Servier Clinical Trial Data website 

Study Data/Documents: Individual Participant Data Set 

Study Protocol 

Statistical Analysis Plan 

Informed Consent Form 

Clinical Study Report 

study-level clinical trial data 

• Responsible Party: Institut de Recherches Internationales Servier
• ClinicalTrials.gov Identifier: NCT04067518
• Other Study ID Numbers: SHP674-201/CL1-95014-001
• First Posted: August 26, 2019
• Results First Posted: June 10, 2022
• Last Update Posted: August 31, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Plan Description

Qualified scientific and medical researchers can request access to anonymized participant-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 participants:

• sponsored by Servier
• with a first participant 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.

• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (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.
• URL: https://clinicaltrials.servier.com/

• 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.: Yes

Keywords provided by Servier ( Institut de Recherches Internationales Servier ):

Acute Lymphoblastic Leukemia

Additional relevant MeSH terms:

Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Pegaspargase; Antineoplastic Agents