Clinical trial with GRASPA, Red Blood cells encapsulating L-Asparaginase, in patients affected by Acute Myeloid leukemia

Phase 1

Conditions: Acute Myeloid Leukaemia
MedDRA version: 18.1Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 100000004864
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2012-002026-78-DE

Lead Sponsor: ERYTECH Pharma

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 123

Inclusion Criteria

- Patients aged from 65 to 85 years old included
- Newly diagnosed Acute Myeloid Leukemia (AML) or post myelodysplastic syndrome diagnosed in the 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:
o Dependence in activities of daily living owing to the presence of comorbidities other than those resulting from the deterioration caused by the neoplastic disease.
o 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
o 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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 123

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:
o Myelodysplastic syndrome diagnosed more than 6 months before study entry
o Myeloproliferative syndrome
• Prior therapy to AML (standard therapy or investigational agents)
• Inadequate organ function :
o 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.
o Serum creatinine concentration > 2 x ULN (Upper Limit of Normal)
o AST or ALT levels > 3.5xULN or 5xULN if related to AML
o Total bilirubin > 2 x ULN
o INR > 1.5, unless patient under chronic treatment with anticoagulants (in this case, INR should be within expected ranges for the specific condition)
o Insulin-dependent or uncontrolled diabetes mellitus
• Concurrent malignancies other than AML requiring chemotherapy
• Severe active infection, HIV seropositivity, known active hepatitis B or
C infection
• Known or suspected hypersensitivity or intolerance to mannitol
• Contraindication to cytarabine treatment (according to country specific
approved Cytarabine SPC)
• Breastfeeding or lactating women

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate Overall Survival (OS) in AML patients 65 to 85 years old unfit for intensive chemotherapy, when treated with GRASPA (L-asparaginase encapsulated in erythrocytes) plus low-dose cytarabine compared to low-dose cytarabine alone.;Secondary Objective: To evaluate<br>- Response to treatment<br>- Progression-free Survival (PFS)<br>- Relapse Free Survival<br>- Patient transfusion needs<br>- Patients Quality of life evolution<br>- Number of hospitalization<br>- Safety of GRASPA in combination with cytarabine<br>- Pharmacokinetic and pharmacodynamic parameters of GRASPA<br>- Immunogenicity of GRASPA<br>- Asparagine Synthetase exploration (in bone marrow)<br>- Biomarker cytogenetic testing;Primary end point(s): Overall survival (OS) defined as the time elapsed between randomization<br>and death from any cause;Timepoint(s) of evaluation of this end point: The primary analysis for OS will take place once all patients have completed 12 months in the study

Secondary Outcome Measures

Name	Time	Method

Related Trials