ABT-751 With Chemotherapy for Relapsed Pediatric ALL

• Dose Limiting Toxicity [ Time Frame: Each dose level is evaluated ] [ Designated as safety issue: Yes ]
• Maximum Tolerated Dose [ Time Frame: Each dose level is evaluated ] [ Designated as safety issue: Yes ]

• Dose Limiting Toxicity
• Maximum Tolerated Dose

• Rate of Remission [ Time Frame: Patients on each dose level will be evaluated for rate of remission. ] [ Designated as safety issue: No ]
• Pharmacokinetic profile on blood and CSF [ Time Frame: Results will be evaluated upon completion of enrollment to the study. ] [ Designated as safety issue: No ]

• Rate of Remission
• Pharmacokinetic profile on blood and CSF

This is a phase I/II study of an investigational drug called ABT-751, produced by Abbott Laboratories, given in combination with chemotherapy drugs used to treat acute lymphoblastic leukemia (ALL) that has come back (recurred). The phase I portion of this study is being done to find the highest dose of ABT-751 that can be given safely in combination with other chemotherapy drugs. A safe dose is one that does not result in unacceptable side effects. After a safe dose for ABT-751 given with chemotherapy has been found, the study will add additional patients to find out if ABT-751 (given at the maximal safe dose) when given with additional chemotherapy is an effective therapy for the treatment of children with relapsed ALL. It is expected that approximately 15-35 children and young adults will take part in this study.

All patients will receive the 2 courses of chemotherapy unless medical complications prevent the administration of some of the drugs. Treatment for the first 2 courses of therapy will last about 2 months.

Treatment on this study will consist of a combination of 8 anti-cancer medications. The 8 anticancer medicines are ABT-751, dexamethasone, PEG-asparaginase, doxorubicin, cytarabine (Ara-C), methotrexate (MTX), cyclophosphamide, and 6-thioguanine. All the drugs except ABT-751 are well known anti-cancer drugs and have been used extensively in the treatment of cancer.

During the Phase I portion of this study, when you enroll, you will be given an assigned dose of ABT-751. The dose of ABT-751 will be based on doses given in previous studies done with adults and children. At each dose level of ABT-751, between 3 and 6 children will receive ABT-751 in combination with chemotherapy. If the side effects are not too severe, the next group of children will receive a higher dose. The dose will continue to be increased until we find the dose that causes serious side effects. Your dose of ABT-751 will not be increased. If you have bad side effects, your dose may be decreased.

The dose used during the Phase 2 part of this study will be determined by the outcome of the Phase I study. The highest dose used in Phase I that was tolerated without serious side effects will be the one used in Phase 2.

• Recurrent Pediatric ALL
• Relapsed Pediatric ALL
• Acute Lymphoblastic Leukemia
• Refractory Pediatric ALL

• Drug: ABT-751
  Oral capsule to be given daily for 21 days.
• Drug: dexamethasone
  IV or Oral daily for 14 days
• Drug: PEG-asparaginase
  Intramuscular injection
• Drug: doxorubicin
  IV infusion
• Drug: cytarabine
  Intrathecal dose on day 1
• Drug: methotrexate
  Intrathecal dose
• Drug: cyclophosphamide
  Intravenous dose
• Drug: 6-thioguanine
  Oral dose, course #2

This is an abbreviated list...

Inclusion Criteria:

• Patients must be less than 21 years of age to be participate in this study.
• Patients must have relapsed acute lymphoblastic leukemia (ALL) without evidence of central nervous system (CNS) disease.
• Patients must have adequate kidney, heart and liver function.
• Must be able to swallow capsules.

Exclusion Criteria:

• Patients who are pregnant or breast feeding.
• Patients who have an allergy to Asparaginase products or sulfa-containing medications.
• Patients who have an active uncontrolled infection.
• Patients who have numbness or tingling in the hands or feet or constipation.