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NCT Number: NCT01518517

GRASPA (Erythrocytes Encapsulating L-asparaginase) in Patients With Relapse of Acute Lymphoblastic Leukemia

Asparaginase is a cornerstone in the treatment of ALL, but its utility is limited by toxicities including hypersensitivity. Clinical allergy is associated with inactivation of asparaginase by antibodies (A-Abs), which can also neutralize asparaginase without any clinical signs of hypersensitivity (silent inactivation). GRASPA improves pharmacokinetics, tolerability and maintain circulating asparaginase activity due to the protective barrier of the erythrocyte membrane.

This study is run to confirm the benefit/risk profile of GRASPA at 150 IU/kg in combination with the COOPRALL regimen in adults and children patients with relapsed ALL, with or without known hypersensitivity to L-asparaginase.

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Key information

Conditions

Acute Lymphoblastic Leukemia, in Relapse Disease Attributes Hematologic Diseases Hemic and Lymphatic Diseases Immune System Diseases Immunoproliferative Disorders Leukemia Leukemia, Lymphoid Lymphatic Diseases Lymphoproliferative Disorders Neoplasms Neoplasms by Histologic Type Pathologic Processes Pathological Conditions, Signs and Symptoms Precursor Cell Lymphoblastic Leukemia-Lymphoma Recurrence

Age range

1 year–55 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

Hopital Des Enfants Reine Fabiola, Brussels, Belgium

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About this study

This open, randomized international Phase 2/3 study will enrol patients with relapsed ALL. The co-primary endpoints were the duration of asparagine depletion < 2µmol/L and the incidence of asparaginase hypersensitivity during induction. Key secondary endpoints are complete remission (CR), minimal residual disease (MRD), event free survival (EFS) and overall survival (OS).The study was powered to detect 3-fold difference in the incidence of allergic reactions between treatments. patients will be randomized to GRASPA or to Reference L-asparaginase. Patients with history of hypersensitivity to previous L-asparaginase treatment will be treated with GRASPA (exploratory arm)

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Patient from 1 to 55 years old (Children and adolescents from 1 to 17 years/ Adults from 18 to 55 years)
  • Patients with 1st ALL relapse, which could be either isolated bone marrow relapse, or combined (medullary and extra-medullary) relapse, or extra-medullary isolated relapse; or lymphoblastic lymphoma (excepted Burkitt lymphoma) OR Failure to ALL first line treatment (no complete remission obtained)
  • Patient previously treated with free E.Coli L-asparaginase form or pegylated one
  • Performance Status ≤ 2 (WHO score)
  • Patient informed and consent provided (the 2 parents need to consent when children are below 18)

Exclusion criteria

  • ALL t(9;22) and/or BCR-ABL positive (Philadelphia chromosome positive)
  • Patient with 2nd relapse and over
  • Women of childbearing potential without effective contraception as well as pregnant or breast feeding women
  • Patient unable to receive treatments used in global chemotherapy protocols, due to general or visceral conditions such as:Severe cardiac impairment (NYHA grade 3 or 4 cardiomyopathy)/Serum creatinine 2 x ULN unless related to ALL /ALT or AST 5 x ULN unless related to ALL /Pancreatitis history /Other malignancy that ALL / Severe Infection, HIV positive, active hepatitis related to B or C virus infection / Trisomy 21 / Other serious conditions according to investigator's opinion
  • Known grade 4 allergic reaction to E.Coli L-asparaginase (according NCI-CTCAE, Version 3.0)
  • History of grade 3 transfusional incident
  • Presence of specific anti-erythrocyte antibodies preventing from getting a compatible erythrocyte concentrate for the patient
  • Patient under concomitant treatment likely to cause hemolysis
  • Patient undergoing yellow fever vaccination
  • Patient under phenytoin treatment
  • Patient included in previous clinical study less than 6 weeks ago

Treatment and study plan

GRASPA

Drug

one injection of GRASPA 150 IU/kg at each cycle of chemotherapy

Other names: ERY001

L-Asparaginase

Drug

3 to 4 Injections of Native E.coli asparaginase 10000IU/m² (every 3 days) at each cycle of chemotherapy

Other names: KIDROLASE

Primary outcomes

  1. Duration of Asparaginase Activity >100 U/L During Induction

    Time frame: Induction treatment period (i.e. 28 days)

    Co-primary efficacy endpoint: duration in days of asparaginase activity >100 U/L in whole blood during the induction treatment phase: last available date/time of activity >100 UI/L before activity drops below 100 U/L - date/time of first activity >100 UI/L. Asparaginase activity is compared for GRASPA versus native ASNase to demonstrate the non-inferiority of GRASPA.

  2. Allergic Reaction During Induction Phase

    Time frame: Induction treatment period (i.e. 28 days)

    Co-primary safety endpoint: allergic reaction regardless of grade during induction phase. Only those reactions that were reported in relation to the treatment to which the patient was randomised were counted.

Secondary outcomes

  1. Complete Remission (CR)

    Time frame: Induction treatment period (i.e. 28 days)

    CR is defined as, no physical evidence of leukemia, normal CBC, cytologic remission: normally regenerating bone marrow, with <5% leukemic blasts and the absence of detectable CNS or extramedullary disease, evaluated with physical examination and CSF findings, at the end of induction

  2. Overall Survival (OS)

    Time frame: Overall trial period to 36 months

    OS is defined as the time from randomisation or date of inclusion (allergic arm) until death due to any cause. Patients who did not die were censored at 36 months of follow-up or the date of the patient's last visit, whichever was earlier.

  3. Event Free Survival

    Time frame: Overall trial period to 36 months

    EFS is defined as the time from randomisation until the first documented sign of disease relapse or death due to any cause. In line with CHMP guidance (CHMP, 2016), patients who did not achieve CR at the end of the induction period were considered to have had an event at time 0. For the patients enrolled in the GRASPA allergic arm, EFS is defined from the date of inclusion in the study.

    Patients who achieved CR at the end of induction and who did not have a documented relapse or death due to any cause were censored at 36 months of follow-up or the date of the patient's last visit, whichever was earlier.

Sponsors and collaborators

Lead sponsor

ERYtech Pharma

Industry

Registry information

Official study title

Phase 2/3 Study Evaluating Efficacy and Safety of Erythrocytes Encapsulating L-asparaginase (GRASPA)Versus Reference L-asparaginase Treatment in Combination With Standard Polychemotherapy in Patient With First Recurrence of Philadelphia Negative Acute Lymphoblastic Leukemia

Acronym: GRASPIVOTALL

Important dates

Study start
2009
Primary completion
2014
Study completion
2016
First posted
Jan 26, 2012
Registry last updated
Feb 2, 2022

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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