Clinical trial NCT01523782: Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase) in Elderly Patients With First Line Acute Lymphoblastic Leukemia
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-)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Acute Lymphoblastic Leukemia
Keywords: Acute Lymphoblastic leukemia
Elderly patient
Asparaginase
Lead sponsor: ERYtech Pharma
Sponsor class: INDUSTRY
First posted: 2012-02-01
Enrollment: 30
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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-).

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment
timeFrame: 7 days after the first administration of GRASPA® during Induction 1
measure: Safety Endpoint - DLTs Assessed During Induction 1 and Induction 2
timeFrame: Induction 1 and Induction 2
Secondary outcomes:
measure: Plasma Concentrations of Asparagine
timeFrame: Induction 1 & Induction 2
measure: Plasma Concentrations of Aspartic Acid
timeFrame: Induction 1 and Induction 2
measure: Plasma Concentrations of Glutamine
timeFrame: Induction 1 and Induction 2
measure: Plasma Concentrations of Glutamic Acid.
timeFrame: Induction 1 and Induction 2
measure: Cerebral Spinal Fluid Concentrations of Asparagine
timeFrame: Induction 1 and Induction 2
measure: Cerebral Spinal Fluid Concentrations of Aspartic Acid
timeFrame: Induction 1 and Induction 2
measure: Cerebral Spinal Fluid Concentrations of Glutamine
timeFrame: Induction 1 and Induction 2
measure: Cerebral Spinal Fluid Concentrations of Glutamic Acid
timeFrame: Induction 1 and Induction 2
measure: Summary of Free Asparaginase Over Time
timeFrame: Induction 1 and Induction 2
measure: Summary of Encapsulated Asparaginase (U/L) Over Time
timeFrame: Induction 1 and Induction 2
measure: Number of Patients Positive for Anti-L-asparaginase Antibodies
timeFrame: Induction 1 and Induction 2
measure: Number of Participants With Complete Remission (CR) Rate Following Induction 1 and Induction 2
timeFrame: 1 and 2 months
Other outcomes:
Locations:
Study officials:
affiliation: University Hospital, Angers
name: Mathilde Hunault-Berger, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hunault-Berger M, Leguay T, Huguet F, Lepretre S, Deconinck E, Ojeda-Uribe M, Bonmati C, Escoffre-Barbe M, Bories P, Himberlin C, Chevallier P, Rousselot P, Reman O, Boulland ML, Lissandre S, Turlure P, Bouscary D, Sanhes L, Legrand O, Lafage-Pochitaloff M, Bene MC, Liens D, Godfrin Y, Ifrah N, Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). A Phase 2 study of L-asparaginase encapsulated in erythrocytes in elderly patients with Philadelphia chromosome negative acute lymphoblastic leukemia: The GRASPALL/GRAALL-SA2-2008 study. Am J Hematol. 2015 Sep;90(9):811-8. doi: 10.1002/ajh.24093.