GRASPA Treatment for Patients With Acute Myeloblastic Leukemia

NCT ID: NCT01810705

Last Updated: 2022-02-21

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 123 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-02-28
• Study Completion Date: 2017-11-10

Brief Summary

The protocol aims at adding GRASPA (L-asparaginase encapsulated in red blood cells, eryaspase) to standard chemotherapy (low-dose cytarabine) to treat patients older than 65 years diagnosed with AML and unfit for intensive chemotherapy.

Detailed Description

L-asparaginase (ASNase) holds a key role in chemotherapy for Acute Lymphoblastic Leukemia (ALL) in children and young adults. In elderly patients, its efficacy is counterbalanced by its toxicity, which impairs its use. However, a study conducted with GRASPA (L-asparaginase encapsulated in red blood cells, eryaspase) in elderly ALL (study reference "GRASPALL-GRAAL SA2 2008") showed that efficacy/safety profile was positive, paving the way for introducing ASNase benefit into chemotherapy for elderly patients.

In adults, Capizzi (1988) reported a significant benefit of ASNase associated with high-dose cytarabine treatment (HiDAC) in Acute Myeloid Leukemia (AML). Indeed, there was an overall statistically superior complete remission rate for HiDAC/ASNase (40%) vs HiDAC (24%) and an overall survival benefit for patients treated with HiDAC/ASNase (19.6 weeks vs 15.9 weeks).

Another study in elderly patients also displayed positive results for ASNase treatment (Petti, 1989), as well as recent single case reports that point out the potential benefit of ASNase in different AML or mixed lineage leukemia (Horikoshi, 2009; Rubnitz, 2009).

Our preclinical results also showed that an AML cell line and blast cells from the bone marrow of AML patients were sensitive to ASNase in vitro.

However, up to now, the toxicity of ASNase for elderly had prevented its use in this population that represents the majority of AML patients.

Considering the promising results of ASNase for AML treatment and the better safety profile offered by GRASPA (L-aspariginase encapsulated in red blood cells, erysapase), a multicenter, randomized, controlled IIb trial is open for recruitment. Efficacy and tolerability of GRASPA plus low-dose cytarabine will be evaluated versus low-dose cytarabine alone in treatment of AML patients over 65 year-old, unfit for intensive chemotherapy.

One hundred and twenty-three patients (65-85 year-old) newly diagnosed for AML are planned for inclusion in the study.

A 2:1 randomization will be respected (82 patients treated with GRASPA® plus low-dose cytarabine and 41 patients treated with low-dose cytarabine alone). Each patient will be followed for 24 months.

Conditions

Acute Myeloid Leukemia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

GRASPA

patients will receive one injection of GRASPA (100 IU/kg) after each course of low-dose cytarabine (see Arm "Control")

Group Type: EXPERIMENTAL

GRASPA

Intervention Type: DRUG

Patients receiving Intervention (experimental group) will be treated with one injection of graspa per cycle of treatment, each cycle during 28 days, for a duration up to 24 cycles maximum

Control

patients will receive successive courses of low intensive chemotherapy, as subcutaneous low-dose cytarabine 20mg twice daily for 10 days per course (from day 1 to day 10), each course occurring every 28 days, for a duration up to 24 months

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

GRASPA

Patients receiving Intervention (experimental group) will be treated with one injection of graspa per cycle of treatment, each cycle during 28 days, for a duration up to 24 cycles maximum

Intervention Type: DRUG

Other Intervention Names

L-asparaginase encapsulated in red blood cells

Eligibility Criteria

Inclusion Criteria

• Patient > 65 years old and < 85 years old
• Newly diagnosed Acute Myeloid Leukemia (AML) or post myelodysplastic syndrome diagnosed within 6 months prior to study enrollment
• Unfit for intensive chemotherapy (at risk to suffer treatment related pejorative toxicities /early death) due to the presence of one or more of the following criteria: Dependence in activities of daily living owing to the presence of comorbidities other than those resulting from the deterioration caused by the neoplastic disease. Presence in the patient's medical history of three or more of the following comorbidities, even if they are under control with proper treatment: Congestive heart failure, other chronic cardiovascular diseases, chronic obstructive pulmonary disease, cerebrovascular disease, peripheral neuropathy, chronic kidney failure, hypertension, diabetes mellitus, systemic vasculitis, severe arthritis
• Presence of geriatric syndromes such as fecal or urinary incontinence, spontaneous bone fractures, mild and moderate dementia, or patients who fall repeatedly, or, patient unwilling to receive intensive chemotherapy
• Eligible to receive low-dose cytarabine treatment
• ECOG performance status ≤ 2
• Female patients of childbearing potential and males must agree to use adequate contraception (e.g., hormonal or barrier method of birth control; abstinence) for the duration of study treatment and for 6 months after the last dose of Cytarabine or 3 months after last dose of GRASPA (whichever is the longest).
• Negative serum pregnancy test at study entry for female subjects of childbearing potential
• Subscription to social security insurance (if applicable, in accordance with local regulations)
• Ability to understand, and willingness to sign, a written informed consent document and to comply with scheduled visits, treatment plans, laboratory tests, and other study procedures

Exclusion Criteria

• Patients with M3 AML of FAB classification (APL, acute promyelocytic leukemia)
• Patients with AML involving chromosome 16 abnormalities or translocation (8:21) (CBF-AML)
• Patient with secondary AML subsequent to prior malignant blood disorder such as: Myelodysplastic syndrome diagnosed more than 6 months before study entry or Myeloproliferative syndrome
• Prior therapy to AML (standard therapy or investigational agents)
• Inadequate organ function : Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis, Serum creatinine concentration > 2 x ULN (Upper Limit of Normal), AST or ALT levels > 3.5xULN or 5xULN if related to AML, Total bilirubin > 2 x ULN, INR > 1.5, unless patient under chronic treatment with anticoagulants (in this case, INR should be within expected ranges for the specific condition), Insulin-dependent or uncontrolled diabetes mellitus
• Concurrent malignancies other than AML requiring chemotherapy
• Severe active infection, HIV seropositivity, or known active type B or C viral hepatitis
• Known or suspected hypersensitivity or intolerance to mannitol
• Breastfeeding or lactating women

• Minimum Eligible Age: 65 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

ERYtech Pharma

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

X Thomas, Doctor

Role: PRINCIPAL_INVESTIGATOR

Locations

Hôpital l'Archet 1

Nice, Alpes Maritimes, France

Centre Léon Bérard

Lyon, Auvergne-Rhône-Alpes, France

Centre hospitalier Lyon Sud

Pierre-Bénite, Auvergne-Rhône-Alpes, France

Institut Paoli Calmettes

Marseille, Bouche Du Rhone, France

Hôpital JEAN MINJOZ

Besançon, Doubs, France

Hopital Morvan

Brest, Finistere, France

Hôpital Haut-Lévèque

Pessac, Gironde, France

CHRU de Nîmes

Nîmes, Guard, France

Hopital de Hautepierre

Strasbourg, Haut Rhin, France

Hopital De Purpan CHU Toulouse

Toulouse, Haute Garonne, France

Hopital Région d'Annecy

Pringy, Haute Savoie, France

Hôpital Saint Eloi

Montpellier, Hérault, France

Hôtel Dieu - CHU de NANTES

Nantes, Loire Atlantique, France

Chu D'Angers

Angers, Maine Et Loire, France

Hopital de Brabois

Vandœuvre-lès-Nancy, Meurthe Et Moselle, France

Hôpital Claude-Huriez

Lille, Nord, France

Institut de Cancérologie de la Loire

Saint-priest-en-jarez, Pays de la Loire Region, France

CHU Estaing

Clermont-Ferrand, Puy De Dome, France

hopital de Perpignan

Perpignan, Pyrénées Orientales, France

Centre Henri Becquerel

Rouen, Seine Maritime, France

Groupe Hospitalier Sud

Amiens, Somme, France

Countries

France

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

GRASPA-AML2012-01

Identifier Type: -

Identifier Source: org_study_id