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

NCT01523782 | Completed Phase 2 Results DMC

• 1 other identifier: GRASPALL/GRAALLSA2-2008
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

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-).

Conditions

Acute Lymphoblastic Leukemia

Keywords

Acute Lymphoblastic leukemia; Elderly patient; Asparaginase

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (12)

• Plasma Concentrations of Asparagine

  Induction 1 & Induction 2

• Plasma Concentrations of Aspartic Acid

  Induction 1 and Induction 2

• Plasma Concentrations of Glutamine

  Induction 1 and Induction 2

• Plasma Concentrations of Glutamic Acid.

  Induction 1 and Induction 2

• Cerebral Spinal Fluid Concentrations of Asparagine

  Induction 1 and Induction 2

Study Arms (3)

GRASPA 50 IU/kg

EXPERIMENTAL

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.

Drug: GRASPA

GRASPA 100 IU/kg

EXPERIMENTAL

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

Drug: GRASPA

GRASPA 150 IU/kg

EXPERIMENTAL

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

Drug: GRASPA

Interventions

GRASPA DRUG

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

GRASPA 100 IU/kg; GRASPA 150 IU/kg; GRASPA 50 IU/kg

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• ERYtech Pharma: lead

Related Publications (1)

• 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.

  PMID: 26094614 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Results Point of Contact

• Title: Denise Tilton, Global Head Clinical Operations & Program Management
• Organization: ERYTECH Pharma

dtilton@erytech.com

+1 857-706-1587

Study Officials

• Mathilde Hunault-Berger, Professor

  University Hospital, Angers

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Masking Details: Open label
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 16, 2012
• First Posted: February 1, 2012
• Study Start: April 1, 2009
• Primary Completion: January 1, 2011
• Study Completion: October 1, 2012
• Last Updated: October 15, 2021
• Results First Posted: June 14, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share