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Am J Hematol. 2015 Sep;90(9):811-8. doi: 10.1002/ajh.24093.

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.

Author information

1
Haematology Department of Angers, Angers, France.
2
Haematology Department of Bordeaux, Bordeaux, France.
3
Haematology Department of Toulouse, Toulouse, France.
4
Haematology Department of Rouen, Rouen, France.
5
Haematology Department of Besançon, Besançon, France.
6
Haematology Department of Mulhouse, Mulhouse, France.
7
Haematology Department of Nancy, Nancy, France.
8
Haematology Department of Rennes, Rennes, France.
9
Haematology Department of Strasbourg, Strasbourg, France.
10
Haematology Department of Reims, Reims, France.
11
Haematology Department of Nantes, Nantes, France.
12
Haematology Department of Versailles, Versailles, France.
13
Haematology Department of Caen, Caen, France.
14
Haematology Department of Tours, Tours, France.
15
Haematology Department of Limoges, Limoges, France.
16
Haematology Department of Cochin APHP Paris, France.
17
Haematology Department of Perpignan, Perpignan, France.
18
Haematology Department of Saint Antoine APHP Paris, France.
19
Genetic Department of AP-HM Marseille, France.
20
Haematology Department of ERYTECH Pharma, France.
21
Haematology Department of Saint-Louis AP-HP Paris, France.

Abstract

PURPOSE:

The GRASPALL/GRAALL-SA2-2008 Phase II trial evaluated the safety and efficacy of L-asparaginase encapsulated within erythrocytes (GRASPA®) in patients ≥ 55 years with Philadelphia chromosome-negative acute lymphoblastic leukemia.

FINDINGS:

Thirty patients received escalating doses of GRASPA® on Day 3 and 6 of induction Phases 1 and 2. The primary efficacy endpoint was asparagine depletion < 2 µmol/L for at least 7 days. This was reached in 85 and 71% of patients with 100 and 150 IU/kg respectively but not with 50 IU/kg. Grade 3/4 infection, hypertransaminasemia, hyperbilirubinemia and deep vein thrombosis occurred in 77, 20, 7, and 7% of patients, respectively. No allergic reaction or clinical pancreatitis was observed despite 17% of Grade 3/4 lipase elevation. Anti-asparaginase antibodies were detected in 50% of patients and related to a reduction in the duration of asparagine depletion during induction Phase 2 without decrease of encapsulated L-asparaginase activity. Complete remission rate was 70%. With a median follow-up of 42 months, median overall survival was 15.8 and 9.7 months, in the 100 and 150 IU/kg cohorts respectively.

CONCLUSIONS:

The addition of GRASPA®, especially at the 100 IU/kg dose level, is feasible in elderly patients without excessive toxicity and associated with durable asparagine depletion. (clinicaltrials.gov identifier NCT01523782).

PMID:
26094614
DOI:
10.1002/ajh.24093
[Indexed for MEDLINE]
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