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

Status:	Recruiting
Conditions:	Other Indications, Blood Cancer
Therapuetic Areas:	Oncology, Other
Healthy:	No
Age Range:	18 - Any
Updated:	4/21/2016
Start Date:	October 2013
End Date:	September 2017
Contact:	Dan Clancy
Email:	dclancy@erytech.com
Phone:	617-447-4641

Phase I Study of L-asparaginase Encapsulated in Red Blood Cells (ERYASP) in Combination With the CALGB Regimen During Induction and Consolidation Phases for Frontline Therapy Adult Patients With Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia

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.

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.

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.

We found this trial at

sites

Duke University

Durham, North Carolina 27710

(919) 684-8111