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Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase) in Elderly Patients With First Line Acute Lymphoblastic Leukemia

21. September 2021 aktualisiert von: 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-).

Studienübersicht

Status

Abgeschlossen

Bedingungen

Intervention / Behandlung

Detaillierte Beschreibung

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.

Studientyp

Interventionell

Einschreibung (Tatsächlich)

30

Phase

  • Phase 2

Teilnahmekriterien

Forscher suchen nach Personen, die einer bestimmten Beschreibung entsprechen, die als Auswahlkriterien bezeichnet werden. Einige Beispiele für diese Kriterien sind der allgemeine Gesundheitszustand einer Person oder frühere Behandlungen.

Zulassungskriterien

Studienberechtigtes Alter

55 Jahre und älter (Erwachsene, Älterer Erwachsener)

Akzeptiert gesunde Freiwillige

Nein

Studienberechtigte Geschlechter

Alle

Beschreibung

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

Studienplan

Dieser Abschnitt enthält Einzelheiten zum Studienplan, einschließlich des Studiendesigns und der Messung der Studieninhalte.

Wie ist die Studie aufgebaut?

Designdetails

  • Hauptzweck: Behandlung
  • Zuteilung: Nicht randomisiert
  • Interventionsmodell: Parallele Zuordnung
  • Maskierung: Keine (Offenes Etikett)

Waffen und Interventionen

Teilnehmergruppe / Arm
Intervention / Behandlung
Experimental: 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.
Arzneimittel: GRASPA
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
Experimental: 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
Arzneimittel: GRASPA
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
Experimental: 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
Arzneimittel: GRASPA
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

Was misst die Studie?

Primäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment
Zeitfenster: 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
Zeitfenster: 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

Sekundäre Ergebnismessungen

Ergebnis Maßnahme
Maßnahmenbeschreibung
Zeitfenster
Plasma Concentrations of Asparagine
Zeitfenster: 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
Zeitfenster: Induction 1 and Induction 2
Mean plasma concentration of aspartic acid over time.
Induction 1 and Induction 2
Plasma Concentrations of Glutamine
Zeitfenster: Induction 1 and Induction 2
Mean glutamine concentration over time.
Induction 1 and Induction 2
Plasma Concentrations of Glutamic Acid.
Zeitfenster: Induction 1 and Induction 2
Mean glutamic acid concentration over time.
Induction 1 and Induction 2
Cerebral Spinal Fluid Concentrations of Asparagine
Zeitfenster: 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
Zeitfenster: Induction 1 and Induction 2
Mean cerebral spinal fluid aspartic acid concentration
Induction 1 and Induction 2
Cerebral Spinal Fluid Concentrations of Glutamine
Zeitfenster: Induction 1 and Induction 2
Mean cerebral spinal fluid glutamine concentration
Induction 1 and Induction 2
Cerebral Spinal Fluid Concentrations of Glutamic Acid
Zeitfenster: Induction 1 and Induction 2
Mean cerebral spinal fluid glutamic acid concentration
Induction 1 and Induction 2
Summary of Free Asparaginase Over Time
Zeitfenster: Induction 1 and Induction 2
Induction 1 and Induction 2
Summary of Encapsulated Asparaginase (U/L) Over Time
Zeitfenster: Induction 1 and Induction 2
Induction 1 and Induction 2
Number of Patients Positive for Anti-L-asparaginase Antibodies
Zeitfenster: 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
Zeitfenster: 1 and 2 months

CR was defined using:

  • Clinical criteria: disappearance of clinical signs of acute lymphocytic leukemia (ALL)
  • Blood criteria: neutrophils > 1 G/L and platelets >100 G/L
  • Medullary criteria: normally rich bone marrow and percentage of blasts <5%
1 and 2 months

Mitarbeiter und Ermittler

Hier finden Sie Personen und Organisationen, die an dieser Studie beteiligt sind.

Sponsor

ERYtech Pharma

Ermittler

  • Hauptermittler: Mathilde Hunault-Berger, Professor, University Hospital, Angers

Publikationen und hilfreiche Links

Die Bereitstellung dieser Publikationen erfolgt freiwillig durch die für die Eingabe von Informationen über die Studie verantwortliche Person. Diese können sich auf alles beziehen, was mit dem Studium zu tun hat.

Allgemeine Veröffentlichungen

Studienaufzeichnungsdaten

Diese Daten verfolgen den Fortschritt der Übermittlung von Studienaufzeichnungen und zusammenfassenden Ergebnissen an ClinicalTrials.gov. Studienaufzeichnungen und gemeldete Ergebnisse werden von der National Library of Medicine (NLM) überprüft, um sicherzustellen, dass sie bestimmten Qualitätskontrollstandards entsprechen, bevor sie auf der öffentlichen Website veröffentlicht werden.

Haupttermine studieren

Studienbeginn

1. April 2009

Primärer Abschluss (Tatsächlich)

1. Januar 2011

Studienabschluss (Tatsächlich)

1. Oktober 2012

Studienanmeldedaten

Zuerst eingereicht

16. Januar 2012

Zuerst eingereicht, das die QC-Kriterien erfüllt hat

30. Januar 2012

Zuerst gepostet (Schätzen)

1. Februar 2012

Studienaufzeichnungsaktualisierungen

Letztes Update gepostet (Tatsächlich)

15. Oktober 2021

Letztes eingereichtes Update, das die QC-Kriterien erfüllt

21. September 2021

Zuletzt verifiziert

1. Juni 2018

Mehr Informationen

Begriffe im Zusammenhang mit dieser Studie

Schlüsselwörter

Zusätzliche relevante MeSH-Bedingungen

Andere Studien-ID-Nummern

  • GRASPALL/GRAALLSA2-2008

Plan für individuelle Teilnehmerdaten (IPD)

Planen Sie, individuelle Teilnehmerdaten (IPD) zu teilen?

Nein

Beschreibung des IPD-Plans

Not applicable for this study

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