Acute Lymphoblastic LeukemiaPhase 2NCT01523782
Administration of GRASPA (Suspension of Erythrocytes Encapsulating L-asparaginase) in Elderly Patients With First Line Acute Lymphoblastic Leukemia
A Phase 2 study testing GRASPA in people with Acute Lymphoblastic Leukemia, run by ERYtech Pharma.
Trial 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-). Read more about this study
- Who is it for?
- Ages 55 years and older
- Conditions the study is for
- Acute Lymphoblastic Leukemia
- What is being tested?
- GRASPA
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- Apr 2009to Oct 2012
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 55 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
About this study
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-)
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-).
Read the 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.
- Conditions
- Acute Lymphoblastic Leukemia
- Being tested
- GRASPA
- Keywords
- Acute Lymphoblastic leukemia, Elderly patient, Asparaginase
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GRASPADrug
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
| Study group | Role | What they receive |
|---|---|---|
| GRASPA 50 IU/kg | Experimental | 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. Receives: Drug: GRASPA |
| GRASPA 100 IU/kg | Experimental | 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 Receives: Drug: GRASPA |
| GRASPA 150 IU/kg | Experimental | 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 Receives: Drug: GRASPA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment
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®
Measured: 7 days after the first administration of GRASPA® during Induction 1
Safety Endpoint - DLTs Assessed During 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.
Measured: Induction 1 and Induction 2
Secondary outcomes (12)
Plasma Concentrations of Asparagine
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.
Measured: Induction 1 & Induction 2
Plasma Concentrations of Aspartic Acid
Mean plasma concentration of aspartic acid over time.
Measured: Induction 1 and Induction 2
Plasma Concentrations of Glutamine
Mean glutamine concentration over time.
Measured: Induction 1 and Induction 2
Plasma Concentrations of Glutamic Acid.
Mean glutamic acid concentration over time.
Measured: Induction 1 and Induction 2
Cerebral Spinal Fluid Concentrations of Asparagine
Mean cerebral spinal fluid asparagine concentration over time.
Measured: Induction 1 and Induction 2
Cerebral Spinal Fluid Concentrations of Aspartic Acid
Mean cerebral spinal fluid aspartic acid concentration
Measured: Induction 1 and Induction 2
Cerebral Spinal Fluid Concentrations of Glutamine
Mean cerebral spinal fluid glutamine concentration
Measured: Induction 1 and Induction 2
Cerebral Spinal Fluid Concentrations of Glutamic Acid
Mean cerebral spinal fluid glutamic acid concentration
Measured: Induction 1 and Induction 2
Summary of Free Asparaginase Over Time
Measured: Induction 1 and Induction 2
Summary of Encapsulated Asparaginase (U/L) Over Time
Measured: Induction 1 and Induction 2
Number of Patients Positive for Anti-L-asparaginase Antibodies
Evaluation of the number of patients testing positive for anti-asparaginase antibodies.
Measured: Induction 1 and Induction 2
Number of Participants With Complete Remission (CR) Rate Following Induction 1 and Induction 2
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%
Measured: 1 and 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2012 (estimated)
- Study startApr 2009
- Primary completionJan 2011
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- ERYtech Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Mathilde Hunault-Berger, Professor, Principal investigator, University Hospital, Angers
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01523782
- Sponsor's protocol ID
- GRASPALL/GRAALLSA2-2008
- Status last verified
- Jun 2018
- First submitted
- 16 Jan 2012
- Last updated
- 15 Oct 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No: Not applicable for this study
Publications
Hunault-Berger M, Leguay T, Huguet F, Lepretre S, Deconinck E, Ojeda-Uribe M, Bonmati C, Escoffre-Barbe M, Bories P, Himberlin C, Chevallier P, Rousselot P, Reman O, Boulland ML, Lissandre S, Turlure P, Bouscary D, Sanhes L, Legrand O, Lafage-Pochitaloff M, Bene MC, Liens D, Godfrin Y, Ifrah N, Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). A Phase 2 study of L-asparaginase encapsulated in erythrocytes in elderly patients with Philadelphia chromosome negative acute lymphoblastic leukemia: The GRASPALL/GRAALL-SA2-2008 study. Am J Hematol. 2015 Sep;90(9):811-8. doi: 10.1002/ajh.24093.
PubMed 26094614
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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-)
- ClinicalTrials.gov ID
- NCT01523782
- Acronym / sponsor ID
- GRASPALL/GRAALLSA2-2008
- Conditions
- Acute Lymphoblastic Leukemia
- Keywords
- Acute Lymphoblastic leukemia, Elderly patient, Asparaginase
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- ERYtech PharmaIndustry (pharma, biotech, devices)
- Study start
- Apr 2009
- Primary completion
- Jan 2011 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 1 Feb 2012 (estimated)
- Results
- Posted 14 Jun 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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-).
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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| GRASPA 50 IU/kg | Experimental | Drug: GRASPAEach 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 100 IU/kg | Experimental | Drug: GRASPAEach 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 150 IU/kg | Experimental | Drug: GRASPAEach 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 |
Who may qualify
- Ages
- 55 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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 :
- Prior treatment with L-asparaginase (irrespective of the form)
- History of grade 3 transfusional incident (life threatening)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GRASPAEach 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 | Drug | GRASPA 100 IU/kg, GRASPA 150 IU/kg, GRASPA 50 IU/kg |
Primary outcome
Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment
Time frame: 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
Time frame: 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.
12 secondary outcomes
Plasma Concentrations of Asparagine
Time frame: Induction 1 & Induction 2
Plasma Concentrations of Aspartic Acid
Time frame: Induction 1 and Induction 2
Plasma Concentrations of Glutamine
Time frame: Induction 1 and Induction 2
Plasma Concentrations of Glutamic Acid.
Time frame: Induction 1 and Induction 2
Cerebral Spinal Fluid Concentrations of Asparagine
Time frame: Induction 1 and Induction 2
Cerebral Spinal Fluid Concentrations of Aspartic Acid
Time frame: Induction 1 and Induction 2
Cerebral Spinal Fluid Concentrations of Glutamine
Time frame: Induction 1 and Induction 2
Cerebral Spinal Fluid Concentrations of Glutamic Acid
Time frame: Induction 1 and Induction 2
Summary of Free Asparaginase Over Time
Time frame: Induction 1 and Induction 2
Summary of Encapsulated Asparaginase (U/L) Over Time
Time frame: Induction 1 and Induction 2
Number of Patients Positive for Anti-L-asparaginase Antibodies
Time frame: Induction 1 and Induction 2
Number of Participants With Complete Remission (CR) Rate Following Induction 1 and Induction 2
Time frame: 1 and 2 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 26094614Hunault-Berger M, Leguay T, Huguet F, Lepretre S, Deconinck E, Ojeda-Uribe M, Bonmati C, Escoffre-Barbe M, Bories P, Himberlin C, Chevallier P, Rousselot P, Reman O, Boulland ML, Lissandre S, Turlure P, Bouscary D, Sanhes L, Legrand O, Lafage-Pochitaloff M, Bene MC, Liens D, Godfrin Y, Ifrah N, Dombret H; Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL). A Phase 2 study of L-asparaginase encapsulated in erythrocytes in elderly patients with Philadelphia chromosome negative acute lymphoblastic leukemia: The GRASPALL/GRAALL-SA2-2008 study. Am J Hematol. 2015 Sep;90(9):811-8. doi: 10.1002/ajh.24093.
- Individual participant dataSharing planned: No. Not applicable for this study
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mathilde Hunault-Berger, Professor principal investigator
University Hospital, Angers
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing GRASPA in people with Acute Lymphoblastic Leukemia, run by ERYtech Pharma.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jun 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Efficacy Primary Endpoint - Percentage of Patients Responding to Treatment (time frame: 7 days after the first administration of GRASPA® during Induction 1). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01523782, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Oct 2021.