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.

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).

• Authors: Mathilde Hunault-Berger, Thibaut Leguay, Françoise Huguet, Stéphane Leprêtre, Eric Deconinck, Mario Ojeda-Uribe, Caroline Bonmati, Martine Escoffre-Barbe, Pierre Bories, Chantal Himberlin, Patrice Chevallier, Philippe Rousselot, Oumedaly Reman, Marie-Laure Boulland, Severine Lissandre, Pascal Turlure, Didier Bouscary, Laurence Sanhes, Ollivier Legrand, Marina Lafage-Pochitaloff, Marie C Béné, David Liens, Yann Godfrin, Norbert Ifrah, Hervé Dombret, Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL)
• Journal: American journal of hematology (Am J Hematol) Vol. 90 Issue 9 Pg. 811-8 (Sep 2015) ISSN: 1096-8652 [Electronic] United States
• PMID: 26094614 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 Wiley Periodicals, Inc.

Chemical References

• Anti-Bacterial Agents
• Antifungal Agents
• Drug Carriers
• Asparagine
• Asparaginase

Topics

• Aged
• Anti-Bacterial Agents (therapeutic use)
• Antifungal Agents (therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols
• Asparaginase (therapeutic use)
• Asparagine (metabolism)
• Drug Carriers
• Drug Compounding
• Erythrocytes (chemistry, cytology)
• Female
• Gram-Negative Bacterial Infections (complications, drug therapy, mortality, pathology)
• Gram-Positive Bacterial Infections (complications, drug therapy, mortality, pathology)
• Humans
• Male
• Middle Aged
• Mycoses (complications, drug therapy, mortality, pathology)
• Philadelphia Chromosome
• Precursor Cell Lymphoblastic Leukemia-Lymphoma (complications, drug therapy, mortality, pathology)
• Remission Induction
• Survival Analysis