Clinical trial NCT00439296 (phase 1/phase 2, status: terminated)
Conditions: recurrent pediatric all, relapsed pediatric all, acute lymphoblastic leukemia, refractory pediatric all
ICD codes: G47.13, J01.41, K11.22, K12.0, N96, F33.8, G03.2, R63.31, R63.32, G47.33, Z68.51, Z68.54, Z68.52, Z68.53, C91.01, C91.02, C91.00, D46.4, D46.1, D46.A, D46.0, D46.20, D46.21, D46.22
Drugs: abt-751, dexamethasone, peg-asparaginase, doxorubicin, cytarabine, methotrexate, cyclophosphamide, 6-thioguanine
SMILES: COC1=CC=C(C=C1)S(=O)(=O)NC1=C(NC2=CC=C(O)C=C2)N=CC=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, ClCCN(CCCl)P1(=O)NCCCO1, NC1=NC(=S)C2=C(N1)N=CN2
Reason stopped: 
    the study was stopped due to poor accrual and lack of funding.
  
Eligibility criteria:

        Inclusion Criteria

          1. Age Patients must be < 21 years of age when enrolled onto this study. T2005-001
             Protocol version 6/27/2007 17

          2. Diagnosis

             Patients must have relapsed or refractory ALL with a M3 marrow (marrow blasts >25%)
             without clinical evidence of testicular disease or laboratory evidence of CNS disease
             defined as CSF WBC > 5 cells/microliter and blasts. (See Appendix I for method of
             evaluating traumatic lumbar punctures.) Patients in early first relapse (defined as a
             patient who relapses less than 36 months from their initial remission [CR1]) are
             eligible for the phase I portion of the trial.

          3. Performance Level Karnofsky > 60% for patients > 10 years of age and Lansky > 60% for
             patients < 10 years of age.

          4. 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. Prior anthracycline exposure: Patients must have less than 300mg/m2 lifetime
                  exposure of anthracycline chemotherapy. (See Appendix III for calculation
                  criteria)

               2. Stem Cell Transplant (SCT): Patients are eligible 6 months after allogeneic stem
                  cell transplant as long as patients are not actively being treated for
                  graft-versus-host-disease (GvHD).

               3. During the phase I portion of the trial, there is no limit on the number of prior
                  treatment regimens.

               4. During the phase II portion of the trial, patients must have had two or more
                  prior therapeutic attempts defined as:

                    -  Persistent initial disease after two induction attempts, or

                    -  Relapse after one-reinduction attempt (2nd relapse), or

                    -  Persistent disease after first relapse and initial re-induction attempt
                       (Patients in any first relapse are not eligible for the phase II portion of
                       the study)

               5. During the phase II portion of the trial, patients must have no more than 3 prior
                  therapeutic attempts and it must be at least 6 months since the last treatment
                  with a "VPLD" induction/re-induction regimen.

          5. Reproductive Function

               1. Female patients of childbearing potential must have a negative urine or serum
                  pregnancy test confirmed prior to enrollment and within 48 hours of starting
                  therapy.

               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
                  and for 3 months following completion of therapy.

        Exclusion Criteria

          1. Drug Allergies

             Patients will be excluded if they have allergies to the following drugs:

               -  Asparaginase products

               -  Sulfa containing medications

          2. Renal Function Patients will be excluded if their serum creatinine is > the upper
             limit of normal (ULN) for age at the institution's laboratory.

          3. Liver/Pancreatic Function

               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. Grade 3 or greater pancreatitis as defined by the CTCAE v3.0

               4. Amylase or Lipase > 2 x institutional ULN

          4. Cardiac Function Patients will be excluded if their shortening fraction by
             echocardiogram is less than 30%.

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

               1. Patients with grade 2 or greater motor or sensory neuropathy per CTC 3.0
                  criteria.

               2. Patients with grade 2 or greater Ileus (neuroconstipation) per CTC 3.0 criteria.

               3. Patients currently being treated with coumadin.

               4. Patients currently being treated with colchicines.

               5. 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.)

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

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

               8. Patients who, based on BSA and current dose level, require a daily dose of
                  ABT-751 that is less than 25mg per day.

               9. Patients who have started protocol therapy prior to enrollment. Patient may still
                  enroll if IT Ara-C or IT MTX were given within 48 hours of study enrollment as
                  part of the diagnostic lumbar procedure. These patients will not participate in
                  the CSF PK portion of the study.