Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase) in Elderly Patients With First Line Acute Lymphoblastic Leukemia
21 september 2021 bijgewerkt door: 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-).
Studie Overzicht
Toestand
Voltooid
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Ingrijpend
Inschrijving (Werkelijk)
30
Fase
- Fase 2
Deelname Criteria
Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
55 jaar en ouder (Volwassen, Oudere volwassene)
Accepteert gezonde vrijwilligers
Nee
Geslachten die in aanmerking komen voor studie
Allemaal
Beschrijving
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
Studie plan
Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: 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
|
|
Experimenteel: 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
|
|
Experimenteel: 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
|
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
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Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment
Tijdsspanne: 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
|
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Safety Endpoint - DLTs Assessed During Induction 1 and Induction 2
Tijdsspanne: 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.
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Induction 1 and Induction 2
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Plasma Concentrations of Asparagine
Tijdsspanne: 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
|
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Plasma Concentrations of Aspartic Acid
Tijdsspanne: Induction 1 and Induction 2
|
Mean plasma concentration of aspartic acid over time.
|
Induction 1 and Induction 2
|
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Plasma Concentrations of Glutamine
Tijdsspanne: Induction 1 and Induction 2
|
Mean glutamine concentration over time.
|
Induction 1 and Induction 2
|
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Plasma Concentrations of Glutamic Acid.
Tijdsspanne: Induction 1 and Induction 2
|
Mean glutamic acid concentration over time.
|
Induction 1 and Induction 2
|
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Cerebral Spinal Fluid Concentrations of Asparagine
Tijdsspanne: 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
Tijdsspanne: Induction 1 and Induction 2
|
Mean cerebral spinal fluid aspartic acid concentration
|
Induction 1 and Induction 2
|
|
Cerebral Spinal Fluid Concentrations of Glutamine
Tijdsspanne: Induction 1 and Induction 2
|
Mean cerebral spinal fluid glutamine concentration
|
Induction 1 and Induction 2
|
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Cerebral Spinal Fluid Concentrations of Glutamic Acid
Tijdsspanne: Induction 1 and Induction 2
|
Mean cerebral spinal fluid glutamic acid concentration
|
Induction 1 and Induction 2
|
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Summary of Free Asparaginase Over Time
Tijdsspanne: Induction 1 and Induction 2
|
Induction 1 and Induction 2
|
|
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Summary of Encapsulated Asparaginase (U/L) Over Time
Tijdsspanne: Induction 1 and Induction 2
|
Induction 1 and Induction 2
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Number of Patients Positive for Anti-L-asparaginase Antibodies
Tijdsspanne: Induction 1 and Induction 2
|
Evaluation of the number of patients testing positive for anti-asparaginase antibodies.
|
Induction 1 and Induction 2
|
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Number of Participants With Complete Remission (CR) Rate Following Induction 1 and Induction 2
Tijdsspanne: 1 and 2 months
|
CR was defined using:
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1 and 2 months
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Medewerkers en onderzoekers
Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.
Sponsor
Onderzoekers
- Hoofdonderzoeker: Mathilde Hunault-Berger, Professor, University Hospital, Angers
Publicaties en nuttige links
De persoon die verantwoordelijk is voor het invoeren van informatie over het onderzoek stelt deze publicaties vrijwillig ter beschikking. Dit kan gaan over alles wat met het onderzoek te maken heeft.
Studie record data
Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.
Bestudeer belangrijke data
Studie start
1 april 2009
Primaire voltooiing (Werkelijk)
1 januari 2011
Studie voltooiing (Werkelijk)
1 oktober 2012
Studieregistratiedata
Eerst ingediend
16 januari 2012
Eerst ingediend dat voldeed aan de QC-criteria
30 januari 2012
Eerst geplaatst (Schatting)
1 februari 2012
Updates van studierecords
Laatste update geplaatst (Werkelijk)
15 oktober 2021
Laatste update ingediend die voldeed aan QC-criteria
21 september 2021
Laatst geverifieerd
1 juni 2018
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
Andere studie-ID-nummers
- GRASPALL/GRAALLSA2-2008
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Nee
Beschrijving IPD-plan
Not applicable for this study
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