Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase) in Elderly Patients With First Line Acute Lymphoblastic Leukemia
21 de septiembre de 2021 actualizado por: 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-).
Descripción general del estudio
Descripción detallada
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.
Tipo de estudio
Intervencionista
Inscripción (Actual)
30
Fase
- Fase 2
Criterios de participación
Los investigadores buscan personas que se ajusten a una determinada descripción, denominada criterio de elegibilidad. Algunos ejemplos de estos criterios son el estado de salud general de una persona o tratamientos previos.
Criterio de elegibilidad
Edades elegibles para estudiar
55 años y mayores (Adulto, Adulto Mayor)
Acepta Voluntarios Saludables
No
Géneros elegibles para el estudio
Todos
Descripción
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
Plan de estudios
Esta sección proporciona detalles del plan de estudio, incluido cómo está diseñado el estudio y qué mide el estudio.
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: No aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
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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.
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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
|
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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
|
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
|
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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
|
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
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment
Periodo de tiempo: 7 days after the first administration of GRASPA® during Induction 1
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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®
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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
Periodo de tiempo: Induction 1 and Induction 2
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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
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Plasma Concentrations of Asparagine
Periodo de tiempo: Induction 1 & Induction 2
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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.
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Induction 1 & Induction 2
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Plasma Concentrations of Aspartic Acid
Periodo de tiempo: Induction 1 and Induction 2
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Mean plasma concentration of aspartic acid over time.
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Induction 1 and Induction 2
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Plasma Concentrations of Glutamine
Periodo de tiempo: Induction 1 and Induction 2
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Mean glutamine concentration over time.
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Induction 1 and Induction 2
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Plasma Concentrations of Glutamic Acid.
Periodo de tiempo: Induction 1 and Induction 2
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Mean glutamic acid concentration over time.
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Induction 1 and Induction 2
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Cerebral Spinal Fluid Concentrations of Asparagine
Periodo de tiempo: Induction 1 and Induction 2
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Mean cerebral spinal fluid asparagine concentration over time.
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Induction 1 and Induction 2
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Cerebral Spinal Fluid Concentrations of Aspartic Acid
Periodo de tiempo: Induction 1 and Induction 2
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Mean cerebral spinal fluid aspartic acid concentration
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Induction 1 and Induction 2
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Cerebral Spinal Fluid Concentrations of Glutamine
Periodo de tiempo: Induction 1 and Induction 2
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Mean cerebral spinal fluid glutamine concentration
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Induction 1 and Induction 2
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Cerebral Spinal Fluid Concentrations of Glutamic Acid
Periodo de tiempo: Induction 1 and Induction 2
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Mean cerebral spinal fluid glutamic acid concentration
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Induction 1 and Induction 2
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Summary of Free Asparaginase Over Time
Periodo de tiempo: Induction 1 and Induction 2
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Induction 1 and Induction 2
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Summary of Encapsulated Asparaginase (U/L) Over Time
Periodo de tiempo: Induction 1 and Induction 2
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Induction 1 and Induction 2
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Number of Patients Positive for Anti-L-asparaginase Antibodies
Periodo de tiempo: Induction 1 and Induction 2
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Evaluation of the number of patients testing positive for anti-asparaginase antibodies.
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Induction 1 and Induction 2
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Number of Participants With Complete Remission (CR) Rate Following Induction 1 and Induction 2
Periodo de tiempo: 1 and 2 months
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CR was defined using:
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1 and 2 months
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Colaboradores e Investigadores
Aquí es donde encontrará personas y organizaciones involucradas en este estudio.
Patrocinador
Investigadores
- Investigador principal: Mathilde Hunault-Berger, Professor, University Hospital, Angers
Publicaciones y enlaces útiles
La persona responsable de ingresar información sobre el estudio proporciona voluntariamente estas publicaciones. Estos pueden ser sobre cualquier cosa relacionada con el estudio.
Fechas de registro del estudio
Estas fechas rastrean el progreso del registro del estudio y los envíos de resultados resumidos a ClinicalTrials.gov. Los registros del estudio y los resultados informados son revisados por la Biblioteca Nacional de Medicina (NLM) para asegurarse de que cumplan con los estándares de control de calidad específicos antes de publicarlos en el sitio web público.
Fechas importantes del estudio
Inicio del estudio
1 de abril de 2009
Finalización primaria (Actual)
1 de enero de 2011
Finalización del estudio (Actual)
1 de octubre de 2012
Fechas de registro del estudio
Enviado por primera vez
16 de enero de 2012
Primero enviado que cumplió con los criterios de control de calidad
30 de enero de 2012
Publicado por primera vez (Estimar)
1 de febrero de 2012
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
15 de octubre de 2021
Última actualización enviada que cumplió con los criterios de control de calidad
21 de septiembre de 2021
Última verificación
1 de junio de 2018
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
Otros números de identificación del estudio
- GRASPALL/GRAALLSA2-2008
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
No
Descripción del plan IPD
Not applicable for this study
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