This trial is active, not recruiting.

Condition acute myeloid leukemia
Treatment graspa
Phase phase 2
Sponsor ERYtech Pharma
Start date February 2013
End date March 2017
Trial size 123 participants
Trial identifier NCT01810705, GRASPA-AML2012-01


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

The investigators Assume a 75% improvement in median Progression Free survival (PFS) in the L-asparaginase (GRASPA) plus low-dose cytarabine group compared to median PFS in the low-dose cytarabine group (control).

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification safety/efficacy study
Intervention model parallel assignment
Masking open label
Primary purpose treatment
patients will receive one injection of GRASPA (100 IU/kg) after each course of low-dose cytarabine (see Arm "Control")
graspa L-asparaginase encapsulated in red blood cells
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
(No Intervention)
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

Primary Outcomes

change from baseline blast count
time frame: once a month, until disease progression (expected average of 8 months)

Secondary Outcomes

response to treatment
time frame: once a month, until the patient stop treatment (expected average of 8 months)
Overall survival
time frame: 2 years
quality of life
time frame: once a month, until the patient stop treatment (expected average of 8 months)
tolerance to treatment
time frame: once a month, until the patient stop treatment (expected average of 8 months)

Eligibility Criteria

Male or female participants from 65 years up to 85 years old.

Inclusion Criteria: - Patient over 65 years old and less than 85 years old - Newly diagnosed Acute Myeloid Leukemia or post myelodysplastic syndrome diagnosed in the 6 months prior study enrollment - Unfit for intensive chemotherapy (at risk to suffer treatment related pejorative toxicities /early death) or patient unwilling to receive intensive chemotherapy - WHO performance status ≤2 and estimated life expectancy ≥ 3 months - Eligible to receive low-dose cytarabine treatment - Evidence of post-menopausal status for female (absence of menstruation for 12 months) Exclusion Criteria: - Patients with M3 AML of French American British classification ( Acute Promyelocytic Leukemia) - Patients with AML involving chromosome 16 abnormalities or translocation (8:21) - History of grade 3-4 pancreatitis or grade 3-4 thromboembolic event - Presenting with a general or visceral contraindication (Uncontrolled or severe cardiovascular disease ; Plasma creatinine concentration 2 times greater than the upper limit of laboratory ranges ; Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels, 3.5 times greater than the upper limit of laboratory ranges ; Patient presenting evolutive cancer other than AML, except in situ basal-cell carcinoma or in situ cervix cancer ; Severe evolutive infection, or, HIV seropositive or, active hepatitis related to B or C viral infection) - History of Grade 3 Transfusional incident - Has known or suspected hypersensitivity or intolerance to mannitol - Patient presenting contra indication to cytarabine treatment - Participation in an investigational drug study within the 30 days prior to entry

Additional Information

Official title A Multicenter, Open, Randomized, Controlled Phase IIb Trial Evaluating Efficacy and Tolerability of GRASPA (L-asparaginase Encapsulated in Red Blood Cells) Plus Low-dose Cytarabine vs Low-dose Cytarabine Alone, in Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) Elderly Patients, Unfit for Intensive Chemotherapy
Principal investigator X Thomas, Doctor
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 current study with Red Blood Cells (RBC) encapsulating ASNase (GRASPA®) 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. Aim Considering the promising results of ASNase for AML treatment and the better safety profile offered by RBC encapsulating ASNase (GRASPA®), 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. Progression-free survival (time elapsed between treatment initiation and disease progression/death) will be evaluated as a primary endpoint. A 75% improvement in the median progression-free survival is assumed in the experimental group vs control group. Percentages of remission (complete and partial), survival (event-free and overall), patient quality of life, general safety, pharmacodynamic/pharmacokinetic and immunogenicity of GRASPA® will be also evaluated.
Trial information was received from ClinicalTrials.gov and was last updated in August 2016.
Information provided to ClinicalTrials.gov by ERYtech Pharma.