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

Acute Lymphoblastic Leukemia Clinical Trial

Official title:

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-)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01523782
• Other study ID #: GRASPALL/GRAALLSA2-2008
• Status: Completed
• Phase: Phase 2
• Start date: April 2009
• Est. completion date: October 2012

Study information

• Verified date: June 2018
• Source: ERYtech Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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-).

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: October 2012
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Leukemia
• Leukemia, Lymphoid
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• 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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
ERYtech Pharma

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment	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
Primary	Safety Endpoint - DLTs Assessed During 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
Secondary	Plasma Concentrations of Asparagine	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
Secondary	Plasma Concentrations of Aspartic Acid	Mean plasma concentration of aspartic acid over time.	Induction 1 and Induction 2
Secondary	Plasma Concentrations of Glutamine	Mean glutamine concentration over time.	Induction 1 and Induction 2
Secondary	Plasma Concentrations of Glutamic Acid.	Mean glutamic acid concentration over time.	Induction 1 and Induction 2
Secondary	Cerebral Spinal Fluid Concentrations of Asparagine	Mean cerebral spinal fluid asparagine concentration over time.	Induction 1 and Induction 2
Secondary	Cerebral Spinal Fluid Concentrations of Aspartic Acid	Mean cerebral spinal fluid aspartic acid concentration	Induction 1 and Induction 2
Secondary	Cerebral Spinal Fluid Concentrations of Glutamine	Mean cerebral spinal fluid glutamine concentration	Induction 1 and Induction 2
Secondary	Cerebral Spinal Fluid Concentrations of Glutamic Acid	Mean cerebral spinal fluid glutamic acid concentration	Induction 1 and Induction 2
Secondary	Summary of Free Asparaginase Over Time		Induction 1 and Induction 2
Secondary	Summary of Encapsulated Asparaginase (U/L) Over Time		Induction 1 and Induction 2
Secondary	Number of Patients Positive for Anti-L-asparaginase Antibodies	Evaluation of the number of patients testing positive for anti-asparaginase antibodies.	Induction 1 and Induction 2
Secondary	Number of Participants With Complete Remission (CR) Rate Following Induction 1 and Induction 2	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