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

ERYtech Pharma

Status and phase: Completed; Phase 2

Conditions: Acute Lymphoblastic Leukemia

Treatments: Drug: GRASPA

Study type: Interventional

Funder types: Industry

Identifiers

NCT01523782

GRASPALL/GRAALLSA2-2008

Details and patient eligibility

About

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-).

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 55+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 3 patient groups

GRASPA 50 IU/kg

Experimental group

Description:

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.

Treatment:

Drug: GRASPA

GRASPA 100 IU/kg

Experimental group

Description:

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

Treatment:

Drug: GRASPA

GRASPA 150 IU/kg

Experimental group

Description:

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

Treatment:

Drug: GRASPA