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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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ClinicalTrials.gov Identifier: NCT01910428
Recruitment Status : Terminated (Sponsor decision based off site/PI feedback about)
First Posted : July 29, 2013
Last Update Posted : July 5, 2018
Sponsor:
Information provided by (Responsible Party):
ERYtech Pharma

Tracking Information
First Submitted Date  ICMJE July 24, 2013
First Posted Date  ICMJE July 29, 2013
Last Update Posted Date July 5, 2018
Actual Study Start Date  ICMJE October 2013
Actual Primary Completion Date January 25, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 13, 2017)
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
Original Primary Outcome Measures  ICMJE
 (submitted: July 25, 2013)
Number of patients presenting DLT [ Time Frame: Day I-29 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 13, 2017)
  • Overall safety and tolerability [ Time Frame: Duration of study ]
    Number, incidence, type, severity, outcome and causality of AE and SAE
  • Plasma concentrations of asparagine,aspartate,glutamine and glutamate. [ Time Frame: Induction and consolidation phases ]
    Pharmacodynamic parameters (PD)
  • Optional samples for CSF levels of amino acids [ Time Frame: Induction and consolidation phases ]
    PD parameters
  • Red blood cell 24-hour recovery analysis , total, free and encapsulated L-asparaginase [ Time Frame: Day of administration and 24h post administration ]
    Pharmacokinetic parameter
  • Immunogenicity [ Time Frame: Duration of study ]
    Evaluation of the titer of the anti-asparaginase antibody
Original Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2013)
  • Global safety and tolerability [ Time Frame: Day I-29 , Days II-29 and II-56, day III-84 ]
    Number, incidence, type, severity, outcome and causality of AE and SAE
  • Serum concentrations of asparagine,aspartate,glutamine, glutamate and asparaginase [ Time Frame: Day of administration then Day +1,3,7 14 post administration ]
  • concentrations of asparagine,aspartate,glutamine, glutamate in CSF [ Time Frame: Day I, 0-3, Day II-1 and Day II-29 ]
  • 24-hour recovery [ Time Frame: Day of administration and 24h post administration ]
  • Immunogenicity [ Time Frame: Day I-4 and Day I-29 , Day II-15, Day II-29, Day II-43 and Day II-56 ]
    Evaluation of the titer of the anti-asparaginase antibody
Current Other Pre-specified Outcome Measures
 (submitted: March 17, 2016)
Response to treatment [ Time Frame: Induction and consolidation phases ]
Hematological Complete Response rate
Original Other Pre-specified Outcome Measures
 (submitted: July 25, 2013)
Response to treatment [ Time Frame: Induction and consolidation phases ]
Hematological CR, MRD
 
Descriptive Information
Brief Title  ICMJE L-asparaginase Encapsulated in Red Blood Cells (Eryaspase) for Treatment of Adult Patients With ALL or LBL
Official Title  ICMJE 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
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Lymphoblastic Leukemia
  • Lymphoblastic Lymphoma
Intervention  ICMJE Drug: L-asparaginase encapsulated in RBC
  • 50 IU/kg IV
  • 100 IU/kg IV
  • 150 IU/kg IV
  • 200 IU/kg IV
Other Name: ERYASPASE
Study Arms  ICMJE Experimental: L-asparaginase encapsulated in RBC
L-asparaginase encapsulated in RBC dose titration: 50, 100, 150 or 200 IU/kg
Intervention: Drug: L-asparaginase encapsulated in RBC
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: July 2, 2018)
14
Original Estimated Enrollment  ICMJE
 (submitted: July 25, 2013)
18
Actual Study Completion Date  ICMJE March 2018
Actual Primary Completion Date January 25, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01910428
Other Study ID Numbers  ICMJE GRASPALL 2012-09
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party ERYtech Pharma
Study Sponsor  ICMJE ERYtech Pharma
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Richard A LARSON, MD University of Chicago
PRS Account ERYtech Pharma
Verification Date July 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP