Clinical trial NCT00928200 (phase 1, status: terminated)
Conditions: relapsed acute lymphoblastic leukemia, allergy to peg e.coli asparaginase, allergy to native e.coli asparaginase
ICD codes: C83.57, C83.50, C91.01, C91.02, C83.52, C83.56, C83.53
Drugs: erwinase, vincristine, dexamethasone, doxorubicin, cytarabine, methotrexate, triple intrathecal therapy, dexrazoxane
SMILES: CC[C@]1(O)C[C@@H]2CN(C1)CCC1=C(NC3=CC=CC=C13)[C@@](C2)(C(=O)OC)C1=C(OC)C=C2N(C=O)[C@@H]3[C@]4(CCN5CC=C[C@](CC)([C@@H]45)[C@@H](OC(C)=O)[C@]3(O)C(=O)OC)C2=C1, C[C@@H](O[C@H]1OCCN(CC2=NNC(=O)N2)[C@H]1C1=CC=C(F)C=C1)C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F, COC1=CC=CC2=C1C(=O)C1=C(O)C3=C(C[C@](O)(C[C@@H]3O[C@H]3C[C@H](N)[C@H](O)[C@H](C)O3)C(=O)CO)C(O)=C1C2=O, ClCCN(CCCl)P1(=O)NCCCO1, CN(CC1=CN=C2N=C(N)N=C(N)C2=N1)C1=CC=C(C=C1)C(=O)N[C@@H](CCC(O)=O)C(O)=O, C[C@@H](CN1CC(=O)NC(=O)C1)N1CC(=O)NC(=O)C1
Reason stopped: 
    study was terminated due to lack of accrual.
  
Eligibility criteria:

        Inclusion Criteria The eligibility criteria listed below are interpreted literally and
        cannot be waived.

          1. Age Patients must be >1 and < 21 years of age when enrolled onto this study.

          2. Diagnosis Patients must have relapsed or refractory ALL with a M3 marrow (marrow
             blasts >25%) who have had no more than two prior therapeutic attempts. Patients with
             CNS 1, 2, or 3 or testicular disease are eligible. (See section 11.3 for CNS
             definitions)

          3. E. coli Asparaginase Allergy Patients must have a history of prior systemic allergic
             reaction to E. coli asparaginase (native or pegylated), such as urticaria, wheezing,
             or anaphylaxis. Local reactions are not sufficient.

          4. Performance Level Karnofsky > 50% for patients > 10 years of age and Lansky > 50% for
             patients < 10 years of age.

          5. Prior Therapy Patients must have fully recovered from the acute toxic effects of all
             prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study.

               1. Patients may be in first or second relapse and should not have received more than
                  2 induction attempts (including frontline therapy).

               2. Prior anthracycline exposure: Patients must have less than 400mg/m2 lifetime
                  exposure of anthracycline chemotherapy.

               3. Stem Cell Transplant (SCT): Patients are eligible after allogeneic stem cell
                  transplant as long as patients are not actively being treated for
                  graft-versus-host-disease (GvHD).

               4. Patients may have received previous therapy using intramuscular (IM) Erwinase.
                  Patients who have received Erwinase intravenously will be excluded.

          6. Reproductive Function

               1. Female patients of childbearing potential must have a negative urine or serum
                  pregnancy test confirmed prior to enrollment.

               2. Female patients with infants must agree not to breastfeed their infants while on
                  this study.

               3. Male and female patients of child-bearing potential must agree to use an
                  effective method of contraception approved by the investigator during the study.

        Exclusion Criteria

          1. Prior Stroke Patients with a prior history of asparaginase associated stroke are
             excluded. Patients with a history of other asparaginase related deep-venous thromboses
             (including intra-cranial thromboses without evidence of stroke or hemorrhage) are
             eligible.

          2. Down Syndrome Patients with Down Syndrome will be excluded.

          3. Prior Pancreatitis Patients with prior history of Grade 2 or greater
             asparaginase-induced symptomatic pancreatitis will be excluded.

          4. Renal Function Patients will be excluded if their serum creatinine is > 1.5 x the
             upper limit of normal for age at the institution's laboratory.

          5. Liver/Pancreatic Function

             Patients will be excluded if their lab results are as follows:

               1. Direct bilirubin > 1.5x the institutional ULN for age. A total bilirubin result
                  that is less than 1.5 times the institutional ULN for age may be used for
                  eligibility if a direct bilirubin result is not available.

               2. SGPT (ALT) > 4 x institutional ULN

               3. Amylase or Lipase > 2 x institutional ULN

          6. Cardiac Function Patients will be excluded if their shortening fraction by
             echocardiogram is less than the institutional normal for age or an ejection fraction
             by MUGA is less than the institutional normal for age.

          7. Infection Patients will be excluded if they have an active uncontrolled infection.

          8. Patients planning on receiving other investigational agents while on this study. (An
             investigational agent is defined as any drug not currently approved for use in
             humans.)

          9. Patients planning on receiving other anti-cancer therapies while on this study.

         10. Patients who, in the opinion of the investigator, may not be able to comply with the
             safety monitoring requirements of the study.

         11. Patients who have started protocol therapy prior to enrollment. Patient may still
             enroll if IT therapy was given within 72 hours of study enrollment as part of the
             diagnostic lumbar procedure.