Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase) in Elderly Patients With First Line Acute Lymphoblastic Leukemia
21. september 2021 opdateret af: ERYtech Pharma
An Escalating Dose Phase IIa Study of L-Asparaginase Encapsulated in Erythrocytes (GRASPA®) in Association With Polychemotherapy During Induction Phase for Treatment of Elderly Patients With Acute Lymphoblastic Leukaemia (ALL), Aged 55 Years and Over, With Philadelphia Chromosome-negative (ALL Ph-)
The main purpose of this study is to determine the maximum tolerated and efficient dose of GRASPA® in combination with polychemotherapy treatment of elderly patients with ALL, 55 years and over, Philadelphia chromosome-negative (ALL Ph-).
Studieoversigt
Detaljeret beskrivelse
This open label, non randomised, multicentric and national phase IIa study was designed to evaluate the safety and efficacy of GRASPA®, a suspension of red blood cells encapsulating E. Coli L-asparaginase, at different doses and in combination with the polychemotherapy regimen recommended by the European Working Group on Adult ALL (EWALL) for frontline therapy of patients with ALL Ph-, aged 55 years old and over.
Patients with a good performance status (WHO score ≤2) and a newly diagnosed ALL Ph- were treated with the backbone polychemotherapy consisting of a first 4-week induction phase comprising dexamethasone, vincristine and idarubicin, a second 4-week induction phase including cyclophosphamide, cytarabine, a 6-month consolidation phase consisting of 6 alternating cycles with methotrexate, asparaginase and folinic acid (cycles 1, 3 and 5) and high-dose cytarabine (cycles 2, 4 and 6) with Granulocyte colony stimulating factor (G-CSF) support followed by a 16-month maintenance period with mercaptopurine, methotrexate and vincristine/dexamethasone pulses.
GRASPA® was administered on day 3 of induction 1 and on day 6 of induction 2 of the chemotherapy regimen.
Undersøgelsestype
Interventionel
Tilmelding (Faktiske)
30
Fase
- Fase 2
Deltagelseskriterier
Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.
Berettigelseskriterier
Aldre berettiget til at studere
55 år og ældre (Voksen, Ældre voksen)
Tager imod sunde frivillige
Ingen
Køn, der er berettiget til at studere
Alle
Beskrivelse
Inclusion Criteria:
- Patient aged ≥55 years old
- With newly diagnosed ALL without prior treatment
- Capable to receive polychemotherapy (World Health Organization (WHO) performance status ≤2)
- With or without meningeal disease
- Having signed an Informed Consent Form
- Subscribed to social security insurance
Exclusion Criteria:
- ALL translocation(9;22) and/or BCR-ABL (Breakpoint Cluster Region-Abelson) positive
- Performance status incompatible with chemotherapy treatment (WHO score >2)
Patient presenting with a general or visceral contraindication to intensive treatment including :
- Cardiac insufficiency defined as Left Ventricular Ejection Fraction <50% of the theoretical value
- Plasma creatinine concentration 2 times greater than the upper limit of laboratory ranges, except if related to ALL
- Aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT) levels 5 times greater than the upper limit of laboratory ranges, except if related to ALL
- Patient with another evolutive cancer other than ALL
- Severe evolutive infection, or Human Immunodeficiency Virus (HIV) seropositive or, active hepatitis related to B or C viral infection
- Prior treatment with L-asparaginase (irrespective of the form)
- History of grade 3 transfusional incident (life threatening)
- Patient presenting rare and/or dangerous anti-erythrocyte antibodies thus leading to the unavailability of phenotype compatible Red Blood Cells Concentrate
- Patient included in another clinical trial during the last 4 weeks
Studieplan
Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.
Hvordan er undersøgelsen tilrettelagt?
Design detaljer
- Primært formål: Behandling
- Tildeling: Ikke-randomiseret
- Interventionel model: Parallel tildeling
- Maskning: Ingen (Åben etiket)
Våben og indgreb
Deltagergruppe / Arm |
Intervention / Behandling |
|---|---|
|
Eksperimentel: GRASPA 50 IU/kg
Each patient will receive GRASPA 50 IU/kg at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase.
|
Each patient will receive GRASPA at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
|
|
Eksperimentel: GRASPA 100 IU/kg
Each patient will receive GRASPA 100 IU/kg at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
|
Each patient will receive GRASPA at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
|
|
Eksperimentel: GRASPA 150 IU/kg
Each patient will receive GRASPA 150 IU/kg at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
|
Each patient will receive GRASPA at day 3 of the induction 1 phase.
If no toxicity related to investigational product is observed and if the patient's state of health allows it, a second injection, at the identical dose, will be administered at Day 6 of Induction 2 phase
|
Hvad måler undersøgelsen?
Primære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment
Tidsramme: 7 days after the first administration of GRASPA® during Induction 1
|
The main evaluation criterion is a composite efficacy/toxicity criterion.
Efficacy, assessed during induction 1: percentage of patients responding to treatment, i.e. with plasma Asn concentration ≤2µM (depleted), for a duration of at least 7 days after the administration of GRASPA®
|
7 days after the first administration of GRASPA® during Induction 1
|
|
Safety Endpoint - DLTs Assessed During Induction 1 and Induction 2
Tidsramme: Induction 1 and Induction 2
|
Safety: Toxicity, assessed during Induction 1 and Induction 2: according to NCI-CTCAE v3.0 August 2006, with Dose Limiting Toxicities (DLT) defined as: Grade 2 to 4 pancreatic toxicity, Grade 3 or 4 hepatic toxicity, allergic toxicity or deep cerebral thrombosis, known as potentially related to L-asparaginase; hematological toxicity defined as bone marrow blast free aplasia, 30 days following the last injection of chemotherapy, all other Grade 4 toxicities.
|
Induction 1 and Induction 2
|
Sekundære resultatmål
Resultatmål |
Foranstaltningsbeskrivelse |
Tidsramme |
|---|---|---|
|
Plasma Concentrations of Asparagine
Tidsramme: Induction 1 & Induction 2
|
Mean plasma concentration of asparagine over time.
Participants who were Below the Lower Limit of Quantification (BLLQ) were assigned a value of 0.51 μmol/L.
|
Induction 1 & Induction 2
|
|
Plasma Concentrations of Aspartic Acid
Tidsramme: Induction 1 and Induction 2
|
Mean plasma concentration of aspartic acid over time.
|
Induction 1 and Induction 2
|
|
Plasma Concentrations of Glutamine
Tidsramme: Induction 1 and Induction 2
|
Mean glutamine concentration over time.
|
Induction 1 and Induction 2
|
|
Plasma Concentrations of Glutamic Acid.
Tidsramme: Induction 1 and Induction 2
|
Mean glutamic acid concentration over time.
|
Induction 1 and Induction 2
|
|
Cerebral Spinal Fluid Concentrations of Asparagine
Tidsramme: Induction 1 and Induction 2
|
Mean cerebral spinal fluid asparagine concentration over time.
|
Induction 1 and Induction 2
|
|
Cerebral Spinal Fluid Concentrations of Aspartic Acid
Tidsramme: Induction 1 and Induction 2
|
Mean cerebral spinal fluid aspartic acid concentration
|
Induction 1 and Induction 2
|
|
Cerebral Spinal Fluid Concentrations of Glutamine
Tidsramme: Induction 1 and Induction 2
|
Mean cerebral spinal fluid glutamine concentration
|
Induction 1 and Induction 2
|
|
Cerebral Spinal Fluid Concentrations of Glutamic Acid
Tidsramme: Induction 1 and Induction 2
|
Mean cerebral spinal fluid glutamic acid concentration
|
Induction 1 and Induction 2
|
|
Summary of Free Asparaginase Over Time
Tidsramme: Induction 1 and Induction 2
|
Induction 1 and Induction 2
|
|
|
Summary of Encapsulated Asparaginase (U/L) Over Time
Tidsramme: Induction 1 and Induction 2
|
Induction 1 and Induction 2
|
|
|
Number of Patients Positive for Anti-L-asparaginase Antibodies
Tidsramme: Induction 1 and Induction 2
|
Evaluation of the number of patients testing positive for anti-asparaginase antibodies.
|
Induction 1 and Induction 2
|
|
Number of Participants With Complete Remission (CR) Rate Following Induction 1 and Induction 2
Tidsramme: 1 and 2 months
|
CR was defined using:
|
1 and 2 months
|
Samarbejdspartnere og efterforskere
Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.
Sponsor
Efterforskere
- Ledende efterforsker: Mathilde Hunault-Berger, Professor, University Hospital, Angers
Publikationer og nyttige links
Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.
Datoer for undersøgelser
Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.
Studer store datoer
Studiestart
1. april 2009
Primær færdiggørelse (Faktiske)
1. januar 2011
Studieafslutning (Faktiske)
1. oktober 2012
Datoer for studieregistrering
Først indsendt
16. januar 2012
Først indsendt, der opfyldte QC-kriterier
30. januar 2012
Først opslået (Skøn)
1. februar 2012
Opdateringer af undersøgelsesjournaler
Sidste opdatering sendt (Faktiske)
15. oktober 2021
Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier
21. september 2021
Sidst verificeret
1. juni 2018
Mere information
Begreber relateret til denne undersøgelse
Yderligere relevante MeSH-vilkår
Andre undersøgelses-id-numre
- GRASPALL/GRAALLSA2-2008
Plan for individuelle deltagerdata (IPD)
Planlægger du at dele individuelle deltagerdata (IPD)?
Ingen
IPD-planbeskrivelse
Not applicable for this study
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