Back to resultsL-asparaginase Encapsulated in Red Blood Cells (Eryaspase) for Treatment of Adult Patients With ALL or LBL
Primary Purpose
Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma
Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
L-asparaginase encapsulated in RBC
Sponsored by
About this trial
This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring L-asparaginase encapsulated in RBCs, leukemia, lymphoma
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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,
- 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.
Sites / Locations
- University of Chicago
- University of Maryland, Greenebaum Comprehensive Cancer Center
- Monter Cancer Center
- Duke University
- Ohio State University
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
L-asparaginase encapsulated in RBC
Arm Description
L-asparaginase encapsulated in RBC dose titration: 50, 100, 150 or 200 IU/kg
Outcomes
Primary Outcome Measures
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
Secondary Outcome Measures
Overall safety and tolerability
Number, incidence, type, severity, outcome and causality of AE and SAE
Plasma concentrations of asparagine,aspartate,glutamine and glutamate.
Pharmacodynamic parameters (PD)
Optional samples for CSF levels of amino acids
PD parameters
Red blood cell 24-hour recovery analysis , total, free and encapsulated L-asparaginase
Pharmacokinetic parameter
Immunogenicity
Evaluation of the titer of the anti-asparaginase antibody
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01910428
Brief Title
L-asparaginase Encapsulated in Red Blood Cells (Eryaspase) for Treatment of Adult Patients With ALL or LBL
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
Study Type
Interventional
2. Study Status
Record Verification Date
July 2018
Overall Recruitment Status
Terminated
Why Stopped
Sponsor decision based off site/PI feedback about
Study Start Date
October 2013 (Actual)
Primary Completion Date
January 25, 2018 (Actual)
Study Completion Date
March 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ERYtech Pharma
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia, Lymphoblastic Lymphoma
Keywords
L-asparaginase encapsulated in RBCs, leukemia, lymphoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
14 (Actual)
8. Arms, Groups, and Interventions
Arm Title
L-asparaginase encapsulated in RBC
Arm Type
Experimental
Arm Description
L-asparaginase encapsulated in RBC dose titration: 50, 100, 150 or 200 IU/kg
Intervention Type
Drug
Intervention Name(s)
L-asparaginase encapsulated in RBC
Other Intervention Name(s)
ERYASPASE
Intervention Description
50 IU/kg IV
100 IU/kg IV
150 IU/kg IV
200 IU/kg IV
Primary Outcome Measure Information:
Title
Determination of the Maximal Total Dosage (MTD) based on number of patients presenting with related DLT
Description
ERYASPASE administered during the induction and consolidation phases of the standard multi-agent CALBG chemotherapy
Time Frame
Duration of study
Secondary Outcome Measure Information:
Title
Overall safety and tolerability
Description
Number, incidence, type, severity, outcome and causality of AE and SAE
Time Frame
Duration of study
Title
Plasma concentrations of asparagine,aspartate,glutamine and glutamate.
Description
Pharmacodynamic parameters (PD)
Time Frame
Induction and consolidation phases
Title
Optional samples for CSF levels of amino acids
Description
PD parameters
Time Frame
Induction and consolidation phases
Title
Red blood cell 24-hour recovery analysis , total, free and encapsulated L-asparaginase
Description
Pharmacokinetic parameter
Time Frame
Day of administration and 24h post administration
Title
Immunogenicity
Description
Evaluation of the titer of the anti-asparaginase antibody
Time Frame
Duration of study
Other Pre-specified Outcome Measures:
Title
Response to treatment
Description
Hematological Complete Response rate
Time Frame
Induction and consolidation phases
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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
Exclusion Criteria:
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,
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Richard A LARSON, MD
Organizational Affiliation
University of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
University of Maryland, Greenebaum Comprehensive Cancer Center
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Monter Cancer Center
City
Lake Success
State/Province
New York
ZIP/Postal Code
11042
Country
United States
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Facility Name
Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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L-asparaginase Encapsulated in Red Blood Cells (Eryaspase) for Treatment of Adult Patients With ALL or LBL
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