Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase) in Elderly Patients With First Line Acute Lymphoblastic Leukemia
Sponsor
ERYtech Pharma (Industry)
Overall Status
Completed
CT.gov ID
NCT01523782
Collaborator
(none)
30
3
42
Study Details
Study Description
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-).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 2 |
Detailed Description
This open label, non randomised, multicentric and national phase IIa study was designed to evaluate the safety and efficacy of GRASPA®, a suspension of red blood cells encapsulating E. Coli L-asparaginase, at different doses and in combination with the polychemotherapy regimen recommended by the European Working Group on Adult ALL (EWALL) for frontline therapy of patients with ALL Ph-, aged 55 years old and over. Patients with a good performance status (WHO score ≤2) and a newly diagnosed ALL Ph- were treated with the backbone polychemotherapy consisting of a first 4-week induction phase comprising dexamethasone, vincristine and idarubicin, a second 4-week induction phase including cyclophosphamide, cytarabine, a 6-month consolidation phase consisting of 6 alternating cycles with methotrexate, asparaginase and folinic acid (cycles 1, 3 and 5) and high-dose cytarabine (cycles 2, 4 and 6) with Granulocyte colony stimulating factor (G-CSF) support followed by a 16-month maintenance period with mercaptopurine, methotrexate and vincristine/dexamethasone pulses. GRASPA® was administered on day 3 of induction 1 and on day 6 of induction 2 of the chemotherapy regimen.
Study Design
Study Type:
Interventional
Actual Enrollment
:
30 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Masking Description:
Open label
Primary Purpose:
Treatment
Official Title:
An Escalating Dose Phase IIa Study of L-Asparaginase Encapsulated in Erythrocytes (GRASPA®) in Association With Polychemotherapy During Induction Phase for Treatment of Elderly Patients With Acute Lymphoblastic Leukaemia (ALL), Aged 55 Years and Over, With Philadelphia Chromosome-negative (ALL Ph-)
Study Start Date
:
Apr 1, 2009
Actual Primary Completion Date
:
Jan 1, 2011
Actual Study Completion Date
:
Oct 1, 2012
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: GRASPA 50 IU/kg 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
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
|
| Experimental: GRASPA 100 IU/kg 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
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
|
| Experimental: GRASPA 150 IU/kg 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
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
|
Outcome Measures
Primary Outcome Measures
- Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment [7 days after the first administration of GRASPA® during Induction 1]
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®
- Safety Endpoint - DLTs Assessed During Induction 1 and Induction 2 [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.
Secondary Outcome Measures
- Plasma Concentrations of Asparagine [Induction 1 & Induction 2]
Mean plasma concentration of asparagine over time. Participants who were Below the Lower Limit of Quantification (BLLQ) were assigned a value of 0.51 μmol/L.
- Plasma Concentrations of Aspartic Acid [Induction 1 and Induction 2]
Mean plasma concentration of aspartic acid over time.
- Plasma Concentrations of Glutamine [Induction 1 and Induction 2]
Mean glutamine concentration over time.
- Plasma Concentrations of Glutamic Acid. [Induction 1 and Induction 2]
Mean glutamic acid concentration over time.
- Cerebral Spinal Fluid Concentrations of Asparagine [Induction 1 and Induction 2]
Mean cerebral spinal fluid asparagine concentration over time.
- Cerebral Spinal Fluid Concentrations of Aspartic Acid [Induction 1 and Induction 2]
Mean cerebral spinal fluid aspartic acid concentration
- Cerebral Spinal Fluid Concentrations of Glutamine [Induction 1 and Induction 2]
Mean cerebral spinal fluid glutamine concentration
- Cerebral Spinal Fluid Concentrations of Glutamic Acid [Induction 1 and Induction 2]
Mean cerebral spinal fluid glutamic acid concentration
- Summary of Free Asparaginase Over Time [Induction 1 and Induction 2]
- Summary of Encapsulated Asparaginase (U/L) Over Time [Induction 1 and Induction 2]
- Number of Patients Positive for Anti-L-asparaginase Antibodies [Induction 1 and Induction 2]
Evaluation of the number of patients testing positive for anti-asparaginase antibodies.
- Number of Participants With Complete Remission (CR) Rate Following Induction 1 and Induction 2 [1 and 2 months]
CR was defined using: Clinical criteria: disappearance of clinical signs of acute lymphocytic leukemia (ALL) Blood criteria: neutrophils > 1 G/L and platelets >100 G/L Medullary criteria: normally rich bone marrow and percentage of blasts <5%
Eligibility Criteria
Criteria
Ages Eligible for Study:
55 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
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
Exclusion Criteria:
-
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
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- ERYtech Pharma
Investigators
- Principal Investigator: Mathilde Hunault-Berger, Professor, University Hospital, Angers
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
ERYtech Pharma
ClinicalTrials.gov Identifier:
NCT01523782
Other Study ID Numbers:
- GRASPALL/GRAALLSA2-2008
First Posted:
Feb 1, 2012
Last Update Posted:
Oct 15, 2021
Last Verified:
Jun 1, 2018
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by ERYtech Pharma
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg |
|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 |
| Period Title: Overall Study | |||
| STARTED | 3 | 13 | 14 |
| COMPLETED | 2 | 13 | 9 |
| NOT COMPLETED | 1 | 0 | 5 |
Baseline Characteristics
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg | Total |
|---|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 | Total of all reporting groups |
| Overall Participants | 3 | 13 | 14 | 30 |
| Age (years) [Mean (Full Range) ] | ||||
| Mean (Full Range) [years] |
68.33
|
66.92
|
67.00
|
67.10
|
| Sex: Female, Male (Count of Participants) | ||||
| Female |
2
66.7%
|
6
46.2%
|
8
57.1%
|
16
53.3%
|
| Male |
1
33.3%
|
7
53.8%
|
6
42.9%
|
14
46.7%
|
| Region of Enrollment (participants) [Number] | ||||
| France |
3
100%
|
13
100%
|
14
100%
|
30
100%
|
Outcome Measures
| Title | Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment |
|---|---|
| Description | 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® |
| Time Frame | 7 days after the first administration of GRASPA® during Induction 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg |
|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 |
| Measure Participants | 3 | 13 | 14 |
| Count of Participants [Participants] |
0
0%
|
11
84.6%
|
10
71.4%
|
| Title | Safety Endpoint - DLTs Assessed During Induction 1 and Induction 2 |
|---|---|
| Description | 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. |
| Time Frame | Induction 1 and Induction 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg |
|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 |
| Measure Participants | 3 | 13 | 14 |
| Number [DLTs] |
0
|
5
|
17
|
| Title | Plasma Concentrations of Asparagine |
|---|---|
| Description | Mean plasma concentration of asparagine over time. Participants who were Below the Lower Limit of Quantification (BLLQ) were assigned a value of 0.51 μmol/L. |
| Time Frame | Induction 1 & Induction 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. |
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg |
|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 |
| Measure Participants | 3 | 13 | 14 |
| Induction 1, Day 3 |
60.86
(9.38)
|
46.74
(21.44)
|
42.33
(10.98)
|
| Induction 1, Day 4 |
0.51
(0)
|
0.51
(0)
|
0.51
(0)
|
| Induction 1, Day 10 |
17.48
(11.46)
|
1.78
(3.39)
|
3.11
(4.05)
|
| Induction 1, Day 17 |
16.33
(9.62)
|
10.05
(8.10)
|
9.30
(7.39)
|
| Induction 1, Day 22-28 |
24.55
(1.60)
|
20.35
(10.60)
|
18.76
(8.74)
|
| Induction 2, Day 6 |
45.39
(1.24)
|
28.11
(9.74)
|
27.16
(14.45)
|
| Induction 2, Day 7 |
9.41
(12.59)
|
9.44
(16.23)
|
0.51
(0)
|
| Induction 2, Day 13 |
29.47
(34.69)
|
10.37
(11.16)
|
3.79
(6.58)
|
| Induction 2, Day 20 |
34.20
(8.48)
|
13.71
(10.40)
|
12.91
(8.17)
|
| Induction 2, Day 22 to D28 |
46.22
(28.92)
|
17.27
(12.12)
|
17.23
(4.77)
|
| Title | Plasma Concentrations of Aspartic Acid |
|---|---|
| Description | Mean plasma concentration of aspartic acid over time. |
| Time Frame | Induction 1 and Induction 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. |
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg |
|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 |
| Measure Participants | 3 | 13 | 14 |
| Induction 1, D3 |
1.91
(0.28)
|
2.38
(4.39)
|
3.59
(5.03)
|
| Induction 1, D4 |
11.08
(4.14)
|
5.22
(1.81)
|
8.11
(5.50)
|
| Induction 1, D10 |
17.93
(3.65)
|
16.47
(6.17)
|
13.51
(5.16)
|
| Induction 1, D17 |
3.76
(1.39)
|
10.60
(6.02)
|
8.43
(4.58)
|
| Induction 1, D22-28 |
5.17
(1.82)
|
10.27
(9.88)
|
6.93
(5.31)
|
| Induction 2, D6 |
2.32
(0.63)
|
4.17
(4.31)
|
5.08
(3.35)
|
| Induction 2, D7 |
12.06
(6.36)
|
6.35
(3.67)
|
7.59
(3.45)
|
| Induction 2, D13 |
9.07
(8.92)
|
9.82
(6.52)
|
10.07
(5.19)
|
| Induction 2, D20 |
2.56
(0.37)
|
8.39
(6.58)
|
7.06
(5.28)
|
| Induction 2, D22-28 |
3.37
(1.00)
|
11.04
(8.66)
|
6.32
(4.75)
|
| Title | Plasma Concentrations of Glutamine |
|---|---|
| Description | Mean glutamine concentration over time. |
| Time Frame | Induction 1 and Induction 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. |
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg |
|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 |
| Measure Participants | 3 | 13 | 14 |
| Induction 1, D3 |
558.78
(158.02)
|
484.19
(137.05)
|
432.07
(69.93)
|
| Induction 1, D4 |
616.13
(184.59)
|
494.76
(142.95)
|
463.03
(117.79)
|
| Induction 1, D10 |
576.86
(172.51)
|
521.86
(180.41)
|
447.07
(159.93)
|
| Induction 1, D17 |
384.12
(28.05)
|
344.03
(102.95)
|
266.08
(71.48)
|
| Induction 1, D22-28 |
394.53
(21.50)
|
422.76
(175.67)
|
393.87
(78.01)
|
| Induction 2, D6 |
508.99
(17.53)
|
436.71
(140.02)
|
426.28
(72.15)
|
| Induction 2, D7 |
553.63
(71.15)
|
498.41
(131.33)
|
445.00
(145.95)
|
| Induction 2, D13 |
517.42
(50.94)
|
467.52
(136.17)
|
456.52
(113.75)
|
| Induction 2, D20 |
436.17
(15.72)
|
406.62
(101.32)
|
394.51
(69.15)
|
| Induction 2, D22-28 |
530.40
(167.13)
|
504.97
(117.83)
|
441.50
(60.63)
|
| Title | Plasma Concentrations of Glutamic Acid. |
|---|---|
| Description | Mean glutamic acid concentration over time. |
| Time Frame | Induction 1 and Induction 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. |
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg |
|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 |
| Measure Participants | 3 | 13 | 14 |
| Induction 1, D3 |
49.96
(17.23)
|
28.68
(18.01)
|
39.87
(49.71)
|
| Induction 1, D4 |
94.73
(35.53)
|
54.38
(29.68)
|
52.17
(29.01)
|
| Induction 1, D10 |
53.58
(6.94)
|
31.87
(17.41)
|
31.82
(23.20)
|
| Induction 1, D17 |
65.73
(21.31)
|
39.71
(27.67)
|
31.57
(23.33)
|
| Induction 1, D22-28 |
42.83
(2.56)
|
46.74
(27.49)
|
36.49
(22.90)
|
| Induction 2, D6 |
58.94
(37.41)
|
53.88
(29.03)
|
55.94
(32.51)
|
| Induction 2, D7 |
77.11
(29.37)
|
63.51
(35.37)
|
83.98
(49.74)
|
| Induction 2, D13 |
34.70
(9.57)
|
53.64
(27.70)
|
52.24
(23.91)
|
| Induction 2, D20 |
27.83
(7.63)
|
42.86
(20.70)
|
35.09
(14.87)
|
| Induction 2, D22-28 |
56.21
(1.85)
|
47.92
(31.07)
|
42.62
(11.94)
|
| Title | Cerebral Spinal Fluid Concentrations of Asparagine |
|---|---|
| Description | Mean cerebral spinal fluid asparagine concentration over time. |
| Time Frame | Induction 1 and Induction 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. |
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg |
|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 |
| Measure Participants | 2 | 12 | 9 |
| Induction 1, D2 |
5.98
(0.63)
|
8.35
(3.20)
|
6.06
(3.17)
|
| Induction 1, D9 |
6.57
(2.72)
|
1.47
(1.28)
|
1.61
(1.09)
|
| Induction 2, D2 |
6.24
(1.07)
|
6.42
(2.62)
|
7.59
(5.58)
|
| Induction 2, D9 |
5.09
(2.99)
|
2.74
(4.24)
|
0.52
(0.03)
|
| Title | Cerebral Spinal Fluid Concentrations of Aspartic Acid |
|---|---|
| Description | Mean cerebral spinal fluid aspartic acid concentration |
| Time Frame | Induction 1 and Induction 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. |
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg |
|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 |
| Measure Participants | 2 | 12 | 9 |
| Induction 1, D2 |
.95
(0.00)
|
.95
(0.00)
|
.95
(0.01)
|
| Induction 1, D9 |
.95
(0.00)
|
1.04
(0.32)
|
1.10
(0.46)
|
| Induction 2, D2 |
.95
(0.00)
|
.95
(0.00)
|
1.35
(0.98)
|
| Induction 2, D9 |
.95
(0.00)
|
1.09
(0.26)
|
.95
(0.00)
|
| Title | Cerebral Spinal Fluid Concentrations of Glutamine |
|---|---|
| Description | Mean cerebral spinal fluid glutamine concentration |
| Time Frame | Induction 1 and Induction 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. |
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg |
|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 |
| Measure Participants | 2 | 12 | 9 |
| Induction 1, D2 |
270.57
(108.21)
|
441.34
(239.50)
|
408.56
(116.84)
|
| Induction 1, D9 |
395.76
(32.50)
|
363.40
(142.12)
|
360.57
(99.56)
|
| Induction 2, D2 |
345.41
(4.13)
|
358.90
(107.03)
|
378.14
(70.19)
|
| Induction 2, D9 |
372.56
(15.67)
|
420.96
(93.42)
|
351.30
(44.86)
|
| Title | Cerebral Spinal Fluid Concentrations of Glutamic Acid |
|---|---|
| Description | Mean cerebral spinal fluid glutamic acid concentration |
| Time Frame | Induction 1 and Induction 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. |
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg |
|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 |
| Measure Participants | 2 | 12 | 9 |
| Induction 1, D2 |
91.55
(39.44)
|
91.98
(85.00)
|
61.48
(53.96)
|
| Induction 1, D9 |
132.53
(15.09)
|
71.78
(38.44)
|
43.93
(30.53)
|
| Induction 2, D2 |
69.35
(5.70)
|
52.89
(24.63)
|
41.24
(20.18)
|
| Induction 2, D9 |
62.04
(8.37)
|
60.30
(28.32)
|
47.02
(39.12)
|
| Title | Summary of Free Asparaginase Over Time |
|---|---|
| Description | |
| Time Frame | Induction 1 and Induction 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. |
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg |
|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 |
| Measure Participants | 3 | 13 | 14 |
| Induction 1, D3 |
3.33
(0.00)
|
3.38
(0.16)
|
3.33
(0.00)
|
| Induction 1, D4 |
2.21
(0.57)
|
6.87
(5.77)
|
4.96
(2.63)
|
| Induction 1, D10 |
0.48
(0.09)
|
0.53
(0.23)
|
0.51
(0.30)
|
| Induction 1, D17 |
0.73
(0.38)
|
0.34
(0.10)
|
0.42
(0.26)
|
| Induction 1, D22-28 |
0.66
(0.11)
|
0.59
(0.37)
|
0.49
(0.32)
|
| Induction 2, D6 |
3.33
(0.00)
|
1.19
(1.03)
|
0.52
(0.18)
|
| Induction 2, D7 |
1.47
(1.65)
|
3.50
(2.86)
|
4.96
(3.78)
|
| Induction 2, D13 |
0.35
(0.02)
|
0.52
(0.35)
|
0.45
(0.38)
|
| Induction 2, D20 |
0.45
(0.04)
|
0.46
(0.42)
|
0.24
(0.07)
|
| Induction 2, D22-28 |
0.49
(0.00)
|
0.68
(0.95)
|
0.35
(0.10)
|
| Title | Summary of Encapsulated Asparaginase (U/L) Over Time |
|---|---|
| Description | |
| Time Frame | Induction 1 and Induction 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. |
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg |
|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 |
| Measure Participants | 3 | 13 | 14 |
| Induction 1, D3 |
72.50
(0.00)
|
239.49
(602.11)
|
72.50
(0.00)
|
| Induction 1, D4 |
915.32
(137.09)
|
1308.48
(490.99)
|
1795.03
(564.74)
|
| Induction 1, D10 |
579.22
(129.99)
|
1105.24
(339.77)
|
1309.08
(497.53)
|
| Induction 1, D17 |
402.41
(181.91)
|
790.39
(193.78)
|
793.97
(291.67)
|
| Induction 1, D22-28 |
383.59
(62.77)
|
571.49
(225.69)
|
629.35
(253.60)
|
| Induction 2, D6 |
72.50
(0.00)
|
382.51
(275.00)
|
524.37
(164.72)
|
| Induction 2, D7 |
722.57
(120.11)
|
1223.20
(323.83)
|
1913.32
(788.45)
|
| Induction 2, D13 |
714.90
(49.91)
|
1051.64
(285.32)
|
1536.06
(401.09)
|
| Induction 2, D20 |
556.00
(52.10)
|
745.22
(288.06)
|
1191.24
(450.38)
|
| Induction 2, D22-28 |
509.20
(0)
|
673.64
(307.10)
|
813.98
(240.88)
|
| Title | Number of Patients Positive for Anti-L-asparaginase Antibodies |
|---|---|
| Description | Evaluation of the number of patients testing positive for anti-asparaginase antibodies. |
| Time Frame | Induction 1 and Induction 2 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The participant numbers in some of the rows below differ from the overall participant numbers analyzed because we are missing the values from some of those time points. |
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg |
|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 |
| Measure Participants | 3 | 13 | 14 |
| Induction 1, D3 |
0
0%
|
0
0%
|
0
0%
|
| Induction 1, D4 |
0
0%
|
0
0%
|
0
0%
|
| Induction 1, D22-28 |
0
0%
|
1
7.7%
|
1
7.1%
|
| Induction 2, D6 |
0
0%
|
0
0%
|
1
7.1%
|
| Induction 2, D22-28 |
1
33.3%
|
4
30.8%
|
5
35.7%
|
| Title | Number of Participants With Complete Remission (CR) Rate Following Induction 1 and Induction 2 |
|---|---|
| Description | CR was defined using: Clinical criteria: disappearance of clinical signs of acute lymphocytic leukemia (ALL) Blood criteria: neutrophils > 1 G/L and platelets >100 G/L Medullary criteria: normally rich bone marrow and percentage of blasts <5% |
| Time Frame | 1 and 2 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| 28 patients were analyzed for CR after Induction 1 (2 pts in 50 IU/kg; 13 pts in 100 IU/kg; 13 pts in 150 IU/kg). 22 patients were analyzed for CR after Induction 2 (2 pts in 50 IU/kg; 11 pts in 100 IU/kg; 9 pts in 150 IU/kg). |
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg |
|---|---|---|---|
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 |
| Measure Participants | 2 | 13 | 13 |
| Participants who met CR criteria at Induction 1 |
2
66.7%
|
10
76.9%
|
8
57.1%
|
| Participants who met CR criteria at Induction 2 |
2
66.7%
|
10
76.9%
|
7
50%
|
Adverse Events
| Time Frame | The period of adverse event (AE) reporting was from the patient inclusion until the end of the product safety follow-up, reached 2 months after the last GRASPA® administration, thus theoretically corresponding to the end of the 2nd cycle of consolidation (Visit V12). | |||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Some Adverse Events were monitored/assessed without regard to the specific Adverse Event Term (i.e. "Gastrointestinal Disorder" and "General Disorder"). | |||||
| Arm/Group Title | GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg | |||
| Arm/Group Description | 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. GRASPA: 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 | 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 GRASPA: 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 | 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 GRASPA: 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 | |||
All Cause Mortality |
||||||
| GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 1/3 (33.3%) | 2/13 (15.4%) | 3/14 (21.4%) | |||
Serious Adverse Events |
||||||
| GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 13/13 (100%) | 13/14 (92.9%) | |||
| Blood and lymphatic system disorders | ||||||
| Febrile bone marrow aplasia | 1/3 (33.3%) | 3/13 (23.1%) | 1/14 (7.1%) | |||
| Bone marrow failure | 0/3 (0%) | 2/13 (15.4%) | 0/14 (0%) | |||
| Pancytopenia | 0/3 (0%) | 0/13 (0%) | 1/14 (7.1%) | |||
| Thrombocytopenia | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Cardiac disorders | ||||||
| Arrythmia | 1/3 (33.3%) | 0/13 (0%) | 0/14 (0%) | |||
| Gastrointestinal disorders | ||||||
| Gastrointestinal haemorrhage | 0/3 (0%) | 1/13 (7.7%) | 1/14 (7.1%) | |||
| Faecaloma | 1/3 (33.3%) | 0/13 (0%) | 0/14 (0%) | |||
| Haemmorhoids | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Rectal haemorrhage | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| General disorders | ||||||
| Generalised oedema | 0/3 (0%) | 0/13 (0%) | 1/14 (7.1%) | |||
| Infusion site ulcer | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Multi-organ failure | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Hepatobiliary disorders | ||||||
| Cytolytic hepatitis | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Immune system disorders | ||||||
| Drug hypersensitivity | 0/3 (0%) | 2/13 (15.4%) | 4/14 (28.6%) | |||
| Infections and infestations | ||||||
| Septic Shock | 0/3 (0%) | 3/13 (23.1%) | 3/14 (21.4%) | |||
| Escherichia sepsis | 1/3 (33.3%) | 2/13 (15.4%) | 0/14 (0%) | |||
| Aspergillosis | 0/3 (0%) | 1/13 (7.7%) | 1/14 (7.1%) | |||
| Bronchopulmonary aspergillosis | 0/3 (0%) | 1/13 (7.7%) | 1/14 (7.1%) | |||
| Pneumonia herpes viral | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Sepsis | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Bacterial Sepsis | 1/3 (33.3%) | 0/13 (0%) | 0/14 (0%) | |||
| Cellulitis | 0/3 (0%) | 0/13 (0%) | 1/14 (7.1%) | |||
| Citrobacter infection | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Diverticulitis | 1/3 (33.3%) | 0/13 (0%) | 0/14 (0%) | |||
| Escherichia bacteraemia | 0/3 (0%) | 0/13 (0%) | 1/14 (7.1%) | |||
| Herpes zoster | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Klebsiella sepsis | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Lung infection | 0/3 (0%) | 0/13 (0%) | 1/14 (7.1%) | |||
| Pneumocystitis jroveci infection | 1/3 (33.3%) | 0/13 (0%) | 0/14 (0%) | |||
| Pseudomonal sepsis | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Staphylococcal sepsis | 0/3 (0%) | 0/13 (0%) | 1/14 (7.1%) | |||
| Stenotrophomonas sepsis | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Investigations | ||||||
| Antithrombin III decreased | 0/3 (0%) | 0/13 (0%) | 2/14 (14.3%) | |||
| Pancreatic enzymes increased | 0/3 (0%) | 0/13 (0%) | 1/14 (7.1%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypoalbuminemia | 0/3 (0%) | 0/13 (0%) | 1/14 (7.1%) | |||
| Tumor lysis syndrome | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Hypernatremia | 0/3 (0%) | 0/13 (0%) | 1/14 (7.1%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Leukemia recurrent | 1/3 (33.3%) | 6/13 (46.2%) | 5/14 (35.7%) | |||
| Myelodysplastic syndrome | 0/3 (0%) | 0/13 (0%) | 1/14 (7.1%) | |||
| Nervous system disorders | ||||||
| Metabolic encephalopathy | 0/3 (0%) | 0/13 (0%) | 1/14 (7.1%) | |||
| Renal and urinary disorders | ||||||
| Renal failure | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Lung disorder | 0/3 (0%) | 3/13 (23.1%) | 0/14 (0%) | |||
| Haemoptysis | 0/3 (0%) | 2/13 (15.4%) | 0/14 (0%) | |||
| Pulmonary oedema | 0/3 (0%) | 0/13 (0%) | 1/14 (7.1%) | |||
| Vascular disorders | ||||||
| Cerebrovascualr accident | 0/3 (0%) | 0/13 (0%) | 2/14 (14.3%) | |||
| Subarachnoid haemorrhage | 0/3 (0%) | 0/13 (0%) | 1/14 (7.1%) | |||
| Subclavian vein thrombosis | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Venous thrombosis | 0/3 (0%) | 0/13 (0%) | 1/14 (7.1%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| GRASPA 50 IU/kg | GRASPA 100 IU/kg | GRASPA 150 IU/kg | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 13/13 (100%) | 14/14 (100%) | |||
| Blood and lymphatic system disorders | ||||||
| Febrile bone marrow aplasia | 1/3 (33.3%) | 3/13 (23.1%) | 4/14 (28.6%) | |||
| Febrile neutropenia | 0/3 (0%) | 1/13 (7.7%) | 2/14 (14.3%) | |||
| Gastrointestinal disorders | ||||||
| Gastrointestinal disorders | 1/3 (33.3%) | 3/13 (23.1%) | 2/14 (14.3%) | |||
| General disorders | ||||||
| General disorder | 0/3 (0%) | 3/13 (23.1%) | 2/14 (14.3%) | |||
| Hepatobiliary disorders | ||||||
| Cytolytic hepatitis | 1/3 (33.3%) | 3/13 (23.1%) | 4/14 (28.6%) | |||
| Hyperbilirubinaemia | 0/3 (0%) | 2/13 (15.4%) | 1/14 (7.1%) | |||
| Immune system disorders | ||||||
| Drug hypersensitivity | 1/3 (33.3%) | 2/13 (15.4%) | 4/14 (28.6%) | |||
| Infections and infestations | ||||||
| Septic Shock | 0/3 (0%) | 3/13 (23.1%) | 3/14 (21.4%) | |||
| Aspergillosis | 1/3 (33.3%) | 2/13 (15.4%) | 1/14 (7.1%) | |||
| Bronchopulmonary aspergillosis | 0/3 (0%) | 1/13 (7.7%) | 2/14 (14.3%) | |||
| Escherichia sepsis | 1/3 (33.3%) | 2/13 (15.4%) | 0/14 (0%) | |||
| Lung infection | 0/3 (0%) | 1/13 (7.7%) | 2/14 (14.3%) | |||
| Oral herpes | 0/3 (0%) | 2/13 (15.4%) | 1/14 (7.1%) | |||
| Investigations | ||||||
| Antithrombin III decreased | 2/3 (66.7%) | 7/13 (53.8%) | 12/14 (85.7%) | |||
| Gamma-glutamyltransferase increased | 1/3 (33.3%) | 6/13 (46.2%) | 4/14 (28.6%) | |||
| Alanine aminotransferase increased | 1/3 (33.3%) | 4/13 (30.8%) | 4/14 (28.6%) | |||
| Blood glucose increased | 1/3 (33.3%) | 4/13 (30.8%) | 4/14 (28.6%) | |||
| Blood bilirubin increased | 0/3 (0%) | 6/13 (46.2%) | 2/14 (14.3%) | |||
| Blood fibrinogen decreased | 0/3 (0%) | 3/13 (23.1%) | 4/14 (28.6%) | |||
| Lipase increased | 1/3 (33.3%) | 2/13 (15.4%) | 3/14 (21.4%) | |||
| Prothrombin level decreased | 0/3 (0%) | 1/13 (7.7%) | 5/14 (35.7%) | |||
| Activated partial thromboplastin time prolonged | 2/3 (66.7%) | 0/13 (0%) | 3/14 (21.4%) | |||
| Blood albumin decreased | 1/3 (33.3%) | 2/13 (15.4%) | 1/14 (7.1%) | |||
| Pancreatic enzymes increased | 0/3 (0%) | 2/13 (15.4%) | 2/14 (14.3%) | |||
| Aspartate aminotransferase increased | 1/3 (33.3%) | 1/13 (7.7%) | 1/14 (7.1%) | |||
| Metabolism and nutrition disorders | ||||||
| Hypoalbuminaemia | 1/3 (33.3%) | 1/13 (7.7%) | 8/14 (57.1%) | |||
| Hyponatraemia | 1/3 (33.3%) | 2/13 (15.4%) | 4/14 (28.6%) | |||
| Hypocalcaemia | 1/3 (33.3%) | 2/13 (15.4%) | 3/14 (21.4%) | |||
| Hypokalaemia | 0/3 (0%) | 4/13 (30.8%) | 2/14 (14.3%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Leukemia recurrent | 1/3 (33.3%) | 6/13 (46.2%) | 5/14 (35.7%) | |||
| Nervous system disorders | ||||||
| Nervous system | 1/3 (33.3%) | 2/13 (15.4%) | 2/14 (14.3%) | |||
| Renal and urinary disorders | ||||||
| Renal failure acute | 0/3 (0%) | 1/13 (7.7%) | 1/14 (7.1%) | |||
| Renal failure | 0/3 (0%) | 1/13 (7.7%) | 0/14 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Respiratory disorders | 0/3 (0%) | 4/13 (30.8%) | 1/14 (7.1%) | |||
| Vascular disorders | ||||||
| Vascular disorder | 1/3 (33.3%) | 2/13 (15.4%) | 5/14 (35.7%) | |||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Denise Tilton, Global Head Clinical Operations & Program Management |
|---|---|
| Organization | ERYTECH Pharma |
| Phone | +1 857-706-1587 |
| dtilton@erytech.com |
Responsible Party:
ERYtech Pharma
ClinicalTrials.gov Identifier:
NCT01523782
Other Study ID Numbers:
- GRASPALL/GRAALLSA2-2008
First Posted:
Feb 1, 2012
Last Update Posted:
Oct 15, 2021
Last Verified:
Jun 1, 2018