Acute Lymphoblastic LeukemiaPhase 1NCT01910428
L-asparaginase Encapsulated in Red Blood Cells (Eryaspase) for Treatment of Adult Patients With ALL or LBL
A Phase 1 study testing L-asparaginase encapsulated in RBC in people with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma, run by ERYtech Pharma at 5 sites in United States.
Trial summary
Asparaginase (Asp) is used during the induction phase of ALL treatment for children and young adults. Its efficacy is counterbalanced by its toxicity, mainly in patients 40 years or older. The efficacy rate in older adult population is lower than for children or young adults. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma
- What is being tested?
- L-asparaginase encapsulated in RBC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 5 sitesUnited States
- Study dates
- Oct 2013to Mar 2018
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women aged 18 years and over
- Diagnosis of acute lymphoblastic leukemia or lymphoblastic lymphoma
- Received no more than 1 prior treatment for ALL/LBL
- Note: Patients who have received transplant during 1st remission are excluded since this would be considered a 2nd treatment
- ECOG performance status 0-2
- Signed Informed Consent Form
Who cannot join
- Other serious medical illness other than that treated by this study which would limit survival to <2 years or psychiatric conditions which would prevent informed consent or compliance with treatment.
- Presenting with a general or visceral contraindication to intensive treatment including:
- uncontrolled or severe cardiovascular disease, including recent (<6 months) myocardial infarction or congestive heart failure,
- Current Grade 3 or higher coagulopathy, thrombosis and/or hemostasis disorders,
- Serum creatinine concentration, 1.5 times greater than the upper limit of laboratory normal ranges (ULN), except if related to ALL/LBL,
- total bilirubin 1.5 times greater than the ULN, except if related to ALL/LBL,
Show all 16Show fewer
- transaminases (AST or ALT) levels, 5 times greater than the ULN, except if related to ALL/LBL,
- An uncontrolled bacterial, viral, or fungal infection or an active duodenal ulcer, until these conditions are corrected or controlled.
- History of Grade 3 or higher allergic reaction with prior asparaginase treatment,
- History of allergy to penicillin or related antibiotic
- History of Grade 3 or higher blood transfusion incident according to US Biovigilance Network which refers to any transfusion followed by a major intervention (vasopressors, intubation, transfer to intensive care) to prevent death.
- Presenting with anti-erythrocyte antibodies leading to the unavailability of phenotype compatible red blood cells.
- Participation in a clinical study involving receipt of an investigational drug during the last 30 days.
- Women of childbearing potential without effective contraception as well as pregnant or breast feeding women.
- Patient receiving treatment likely to cause hemolysis or under phenytoin treatment.
- Patient undergoing yellow fever vaccination.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
University of Maryland, Greenebaum Comprehensive Cancer Center
Baltimore, Maryland, 21201
University of Chicago
Chicago, Illinois, 60637
Ohio State University
Columbus, Ohio, 43210
Duke University
Durham, North Carolina, 27705
Monter Cancer Center
Lake Success, New York, 11042
About this study
Official title: A Phase I Study of L-asparaginase Encapsulated in Red Blood Cells (Eryaspase) in Combination With the CALGB Regimen During Induction and Consolidation Phases in the Treatment of Adult Patients With Acute Lymphoblastic Leukemia and Lymphoma
Asparaginase (Asp) is used during the induction phase of ALL treatment for children and young adults. Its efficacy is counterbalanced by its toxicity, mainly in patients 40 years or older. The efficacy rate in older adult population is lower than for children or young adults. A recent review on outcomes in older adults with ALL pointed out that there were significantly more drug reductions, omissions or delays in the older group as compared to younger adults and that asparaginase was the drug most commonly omitted.
The investigational product ERYASPASE is a dispersion for infusion of homologous red blood cells (RBC) encapsulating E. coli L-asparaginase.
Read more
A previous European phase I/II clinical study in children and adults (<55 yo) at first relapse of ALL was conducted to determine the optimal dose of homologous RBC encapsulating native E. coli Asp (GRASPA®) in 24 patients with relapsed ALL. The activity and safety profiles of 3 doses of GRASPA® (50, 100 and 150 IU/kg) in combination with standard chemotherapy were compared to free native Asp. The global safety profile is also improved, reducing hypersensitivity, liver toxicity and coagulation disorders. Study showed that a single dose of GRASPA® 150 IU/kg induced a depletion in plasmatic asparagine for 18.6 days, i.e. similar to that obtained with 8 injections of 10,000 IU/m² of free native Asp. A reduction in the incidence and severity of the allergic reactions and coagulation disorders were observed with GRASPA® (Domenech 2011).
A French phase II study designed to determine the maximum tolerated dose of GRASPA® in combination with a polychemotherapy regimen in ALL patients older than 55 yo at first diagnosis has been performed, and showed that both 100 and 150 IU/kg doses fulfilled the predefined criteria for efficacy and tolerability but the better profile of 100 IU/kg dose was considered the optimal dose in this setting. A phase II/III trial in adult and children patients with relapsed ALL is currently ongoing.
Based on these results, the combination of ERYASPASE with the CALGB chemotherapy regimen appears to be an attractive combination for the treatment of adults patients with ALL/LBL.
Read the detailed description
A phase I study to assess the limiting toxicities, global safety and clinical activity of ERYASPASE, using a dose titration design to confirm that the safety profile of ERYASPASE in combination with the CALGB chemotherapy regimen is similar to that observed in the European chemotherapy regimen. PK/PD and immunogenicity parameters will also be evaluated.
- Being tested
- L-asparaginase encapsulated in RBC
- Keywords
- L-asparaginase encapsulated in RBCs, leukemia, lymphoma
- Medical subject headings
- Precursor Cell Lymphoblastic Leukemia-Lymphoma, Leukemia, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-asparaginase encapsulated in RBCDrug
Also called ERYASPASE
- 50 IU/kg IV
- 100 IU/kg IV
- 150 IU/kg IV
- 200 IU/kg IV
| Study group | Role | What they receive |
|---|---|---|
| L-asparaginase encapsulated in RBC | Experimental | L-asparaginase encapsulated in RBC dose titration: 50, 100, 150 or 200 IU/kg Receives: Drug: L-asparaginase encapsulated in RBC |
What is being measured
The primary outcome is the main question the study is designed to answer.
Determination of the Maximal Total Dosage (MTD) based on number of patients presenting with related DLT
ERYASPASE administered during the induction and consolidation phases of the standard multi-agent CALBG chemotherapy
Measured: Duration of study
Secondary outcomes (5)
Overall safety and tolerability
Number, incidence, type, severity, outcome and causality of AE and SAE
Measured: Duration of study
Plasma concentrations of asparagine,aspartate,glutamine and glutamate.
Pharmacodynamic parameters (PD)
Measured: Induction and consolidation phases
Optional samples for CSF levels of amino acids
PD parameters
Measured: Induction and consolidation phases
Red blood cell 24-hour recovery analysis , total, free and encapsulated L-asparaginase
Pharmacokinetic parameter
Measured: Day of administration and 24h post administration
Immunogenicity
Evaluation of the titer of the anti-asparaginase antibody
Measured: Duration of study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Jul 2013 (estimated)
- Study startOct 2013
- Primary completion25 Jan 2018
- Study completionMar 2018
Why it stopped: Sponsor decision based off site/PI feedback about
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- ERYtech Pharma
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Richard A LARSON, MD, Principal investigator, University of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01910428
- Sponsor's protocol ID
- GRASPALL 2012-09
- Status last verified
- Jul 2018
- First submitted
- 24 Jul 2013
- Last updated
- 5 Jul 2018
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of L-asparaginase Encapsulated in Red Blood Cells (Eryaspase) in Combination With the CALGB Regimen During Induction and Consolidation Phases in the Treatment of Adult Patients With Acute Lymphoblastic Leukemia and Lymphoma
- ClinicalTrials.gov ID
- NCT01910428
- Acronym / sponsor ID
- GRASPALL 2012-09
- Keywords
- L-asparaginase encapsulated in RBCs, leukemia, lymphoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor decision based off site/PI feedback about
- Enrolment
- 14 participants (actual)
- Lead sponsor
- ERYtech PharmaIndustry (pharma, biotech, devices)
- Study start
- Oct 2013 (actual)
- Primary completion
- 25 Jan 2018 (actual)
- Study completion
- Mar 2018 (actual)
- First posted
- 29 Jul 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Asparaginase (Asp) is used during the induction phase of ALL treatment for children and young adults. Its efficacy is counterbalanced by its toxicity, mainly in patients 40 years or older. The efficacy rate in older adult population is lower than for children or young adults. A recent review on outcomes in older adults with ALL pointed out that there were significantly more drug reductions, omissions or delays in the older group as compared to younger adults and that asparaginase was the drug most commonly omitted.
The investigational product ERYASPASE is a dispersion for infusion of homologous red blood cells (RBC) encapsulating E. coli L-asparaginase.
A previous European phase I/II clinical study in children and adults (<55 yo) at first relapse of ALL was conducted to determine the optimal dose of homologous RBC encapsulating native E. coli Asp (GRASPA®) in 24 patients with relapsed ALL. The activity and safety profiles of 3 doses of GRASPA® (50, 100 and 150 IU/kg) in combination with standard chemotherapy were compared to free native Asp. The global safety profile is also improved, reducing hypersensitivity, liver toxicity and coagulation disorders. Study showed that a single dose of GRASPA® 150 IU/kg induced a depletion in plasmatic asparagine for 18.6 days, i.e. similar to that obtained with 8 injections of 10,000 IU/m² of free native Asp. A reduction in the incidence and severity of the allergic reactions and coagulation disorders were observed with GRASPA® (Domenech 2011).
A French phase II study designed to determine the maximum tolerated dose of GRASPA® in combination with a polychemotherapy regimen in ALL patients older than 55 yo at first diagnosis has been performed, and showed that both 100 and 150 IU/kg doses fulfilled the predefined criteria for efficacy and tolerability but the better profile of 100 IU/kg dose was considered the optimal dose in this setting. A phase II/III trial in adult and children patients with relapsed ALL is currently ongoing.
Based on these results, the combination of ERYASPASE with the CALGB chemotherapy regimen appears to be an attractive combination for the treatment of adults patients with ALL/LBL.
Detailed description
A phase I study to assess the limiting toxicities, global safety and clinical activity of ERYASPASE, using a dose titration design to confirm that the safety profile of ERYASPASE in combination with the CALGB chemotherapy regimen is similar to that observed in the European chemotherapy regimen. PK/PD and immunogenicity parameters will also be evaluated.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| L-asparaginase encapsulated in RBC | Experimental | Drug: L-asparaginase encapsulated in RBCL-asparaginase encapsulated in RBC dose titration: 50, 100, 150 or 200 IU/kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Men and women aged 18 years and over
- Diagnosis of acute lymphoblastic leukemia or lymphoblastic lymphoma
- Received no more than 1 prior treatment for ALL/LBL
- Note: Patients who have received transplant during 1st remission are excluded since this would be considered a 2nd treatment
- ECOG performance status 0-2
Key exclusion criteria (16 listed)
- Other serious medical illness other than that treated by this study which would limit survival to <2 years or psychiatric conditions which would prevent informed consent or compliance with treatment.
- Presenting with a general or visceral contraindication to intensive treatment including:
- History of Grade 3 or higher allergic reaction with prior asparaginase treatment,
- History of allergy to penicillin or related antibiotic
- History of Grade 3 or higher blood transfusion incident according to US Biovigilance Network which refers to any transfusion followed by a major intervention (vasopressors, intubation, transfer to intensive care) to prevent death.
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 |
|---|---|---|
| L-asparaginase encapsulated in RBCAlso: ERYASPASE* 50 IU/kg IV * 100 IU/kg IV * 150 IU/kg IV * 200 IU/kg IV | Drug | L-asparaginase encapsulated in RBC |
Primary outcome
Determination of the Maximal Total Dosage (MTD) based on number of patients presenting with related DLT
Time frame: Duration of study
ERYASPASE administered during the induction and consolidation phases of the standard multi-agent CALBG chemotherapy
5 secondary outcomes
Overall safety and tolerability
Time frame: Duration of study
Plasma concentrations of asparagine,aspartate,glutamine and glutamate.
Time frame: Induction and consolidation phases
Optional samples for CSF levels of amino acids
Time frame: Induction and consolidation phases
Red blood cell 24-hour recovery analysis , total, free and encapsulated L-asparaginase
Time frame: Day of administration and 24h post administration
Immunogenicity
Time frame: Duration of study
Results and safety
The study was stopped early (reason given: Sponsor decision based off site/PI feedback about). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2018.
- Individual participant dataSharing planned: Undecided
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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.
Richard A LARSON, MD principal investigator
University of Chicago
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing L-asparaginase encapsulated in RBC in people with Acute Lymphoblastic Leukemia and Lymphoblastic Lymphoma, run by ERYtech Pharma at 5 sites in United States.
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 16 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: stopped early, as of the sponsor's last update on 5 Jul 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Sponsor decision based off site/PI feedback about). Results are not available in the source record.
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?
Determination of the Maximal Total Dosage (MTD) based on number of patients presenting with related DLT (time frame: Duration of study). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 Jul 2018.