GRASPA Treatment for Patients With Acute Myeloblastic Leukemia (ENFORCE)
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|ClinicalTrials.gov Identifier: NCT01810705|
Recruitment Status : Completed
First Posted : March 13, 2013
Last Update Posted : March 29, 2018
|Condition or disease||Intervention/treatment||Phase|
|Acute Myeloid Leukemia||Drug: GRASPA||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||123 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multicenter, Open, Randomized, Controlled Phase IIb Trial Evaluating Efficacy and Tolerability of GRASPA (L-asparaginase Encapsulated in Red Blood Cells, Eryaspase) Plus Low-dose Cytarabine vs Low-dose Cytarabine Alone, in Treatment of Newly Diagnosed Acute Myeloid Leukemia (AML) Elderly Patients, Unfit for Intensive Chemotherapy|
|Actual Study Start Date :||February 2013|
|Actual Primary Completion Date :||November 10, 2017|
|Actual Study Completion Date :||November 10, 2017|
patients will receive one injection of GRASPA (100 IU/kg) after each course of low-dose cytarabine (see Arm "Control")
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
Other Name: L-asparaginase encapsulated in red blood cells
No Intervention: 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
- Overall survival [ Time Frame: Each patient will be followed for a duration of 24 months. ]OS is defined as the time elapsed between randomization and death from any cause.
- Response to treatment [ Time Frame: Each patient will be followed for a duration of 24 months. ]Percentage of patients with Complete remission (CR), Complete remission with incomplete recovery (neutrophil or platelet regeneration, CRi), Partial remission (PR)
- Progression free survival (PFS) [ Time Frame: Each patient will be followed for a duration of 24 months. ]Defined as the time elapsed between randomization and resistant disease or relapse or death from any cause
- Patient quality of life [ Time Frame: Each patient will be followed for a duration of 24 months. ]Collecting survey about patients quality of life
- Safety of GRASPA adverse events and serious adverse events [ Time Frame: Each patient will be followed for a duration of 24 months. ]Number of incidences, type, severity and causality of adverse events / serious adverse events
- Relapse free survival [ Time Frame: Each patient will be followed for a duration of 24 months. ]Defined only for patients who achieve CR or CRi as the time elapsed between date of CR/CRi and date of disease relapse or death from any cause
- Number of hospitalizations [ Time Frame: Each patient will be followed for a duration of 24 months. ]Hospitalizations (except schedule protocol visit during the study)
- Percentage of patients who need transfusions [ Time Frame: Until patient stops treatment (expected average of 8 months) ]Number of transfusions per patient (red blood cells and or platelets)
- Pharmacodynamic and pharmacokinetic parameters of GRASPA [ Time Frame: Until patient stops treatment (expected average of 8 months) ]Plasma concentrations of asparagine, aspartate, glutamine, glutamate, whole blood L- asparaginase activity
- Immunogenicity [ Time Frame: Until patient stops treatment (expected average of 8 months) ]Titer of anti L-asparaginase antibodies
- Asparagine synthetase (optional) [ Time Frame: Until patient stops treatment (expected average of 8 months) ]Asparagine synthetase and in vitro sensitivity to aspariginase on the harvested bone marrow cells
- Biomarker cytogenetic testing (optional) [ Time Frame: Until patient stops treatment (expected average of 8 months) ]Defined as cytogenetic biomarker testing
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01810705
|Principal Investigator:||X Thomas, Doctor|