Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

L-asparaginase Encapsulated in Red Blood Cells for Frontline Therapy of Patients With Phi-neg ALL Older Than 18 yo

Protocol: OSU-13111

Full 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

Purpose

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 ERYASP is a suspension 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.

ERYASP with the CALGB chemotherapy regimen appears to be an attractive combination for 1st

line ALL therapy for adults 18 years or older in the USA.

Study Objective

A phase I study to evaluate the tolerance of ERYASP using a dose titration design to confirm

that the safety profile of ERYASP with the CALGB chemotherapy regimen is similar to that

observed in the European chemotherapy regimen. PK/PD and immunogenicity parameters will also

be evaluated.

Are you eligible?

Inclusion Criteria:

Men and women aged 18 years and over

Diagnosis of acute lymphoblastic leukemia

No prior treatment. Emergency leukapheresis is permissible.

Patient capable to receive multi-agent ALL chemotherapy (ECOG performance status 0-2)

Management throughout the full duration of protocol treatment at a medical facility

having ready access to blood product support and adequately staffed to care for the

severely neutropenic patient with multiple therapy-induced toxicities.

Signed Informed Consent Form

Exclusion Criteria:

ALL t(9;22) or BCR-ABL positive or Burkitt-type ALL [positive for t(8;14), etc.]

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,

pancreatic diseases,

history of coagulopathy or current coagulopathy, thrombosis and/or hemostasis

disorders,

plasma creatinine concentration, 1.5 times greater than the upper limit of

laboratory normal ranges (ULN), except if related to ALL,

total bilirubin 1.5 times greater than the ULN, except if related to ALL,

transaminases (AST or ALT) levels, 5 times greater than the ULN, except if

related to ALL,

previous or concomitant malignancy other than curatively treated carcinoma in

situ of cervix or basal cell carcinoma of the skin, or other cancer if the

patient has been disease free for >5 years,

active uncontrolled bacterial, viral, or fungal infection or an active duodenal

ulcer, until these conditions are corrected or controlled.

Prior treatment with L-asparaginase (irrespective of the form).

History of allergy to penicillin or related antibiotic

History of grade 3 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 rare and/or dangerous anti-erythrocyte antibodies, thus 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.

Acute Lymphoblastic Leukemia Leukemia