Bortezomib With Chemotherapy for Relapsed Pediatric Acute Lymphoblastic Leukemia (ALL)
Condition: Acute Lymphoblastic Leukemia
MeSH terms: Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      This is a Phase I/II study of a drug called bortezomib given in combination with chemotherapy
      drugs used to treat acute lymphoblastic leukemia (ALL) that has come back (recurred).
      Bortezomib is a drug that has been approved by the Food and Drug Administration (FDA) for
      treating adults with multiple myeloma which is a type of blood cancer. Bortezomib has been
      shown to cause cancer cells to die in studies done on animals (mice). Studies have been done
      that have shown that some adults and children with cancer have shown a response to bortezomib
      when it is used alone. Studies have also been done in adults to evaluate the dose of
      bortezomib that can be safely given in combination with other chemotherapy drugs.
    

Detailed description: 
      All patients will receive 1 course of chemotherapy unless medical complications prevent the
      administration of some of the drugs. Treatment will last about 1 month.

      Treatment on this study will consist of a combination of 7 anti-cancer medications. The 7
      anti-cancer medicines are bortezomib, vincristine, dexamethasone, PEG-asparaginase,
      doxorubicin, cytarabine (Ara-C), and methotrexate (MTX).

      If you are in the Phase I portion of this study, you will be given an assigned dose of
      bortezomib. The dose of bortezomib will be based on doses given in previous studies done with
      adults and children. At each dose level of bortezomib, between 3 and 6 children will receive
      bortezomib 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 bortezomib 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.
    

Intervention name(s): Bortezomib; Dexamethasone; PEG-asparaginase; Doxorubicin; Cytarabine; Methotrexate; Vincristine; Triple IT Therapy
Intervention type(s): Drug; Drug; Drug; Drug; Drug; Drug; Drug; Drug
Intervention description(s): Intravenous on days 1, 4, 8 and 11. Dose assigned at study entry.; 10 mg/m2/day divided BID, oral administration for 14 days.; 2500 IU/m2/day, intramuscular injection on Days 2, 8, 15 and 22; 60 mg/m2/day IV over 15 minutes on Day 1; Given intrathecally on Day 1 of course 1 at the dose defined by age below.
30 mg for patients age 1-1.99
50 mg for patients age 2-2.99
70 mg for patients >3 years of age; Given intrathecally to all patients who are CNS 1 at study entry on Day 15 at the dose defined by age below.
8 mg for patients age 1-1.99
10 mg for patients age 2-2.99
12 mg for patients 3-8.99 years of age
15 mg for patients >9 years of age; 1.5 mg/m2/dose IV push (maximum single dose 2 mg) on Days 1, 8, 15 and 22.; Triple IT therapy will be given intrathecally on Day 8, 15, and 22 for patients who are CNS 2 and CNS 3 at study entry. Regimen/dosing as follows:
Methotrexate-
<2 years: 8 mg
2 - <3 y: 10 mg
3 - <9 y: 12 mg
>=9 y: 15 mg
Cytarabine:
<2 years: 16 mg
2 - <3 y: 20 mg
3 - <9 y: 24 mg
>=9 y: 30 mg
Hydrocortisone:
<2 years: 8 mg
2 - <3 y: 10 mg
3 - <9 y: 12 mg
>=9 y: 15 mg
Other intervention name(s): Velcade; Decadron; Oncaspar; Adriamycin; Rubex; Cytosar-U; Ara-C; Arabinosylcytosine; Otrexup; Rasuvo; Rheumatrex; Trexall; Amethopterin; Oncovin; Leurocristine
Intervention MeSH terms: Cytarabine; Dexamethasone; Doxorubicin; Methotrexate; Vincristine; Bortezomib; Asparaginase; Pegaspargase
Allocation: Non-Randomized
Intervention model: Sequential Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Acute Lymphoblastic Leukemia; Pediatrics; Relapsed; Recurrence; Bortezomib; Velcade; Therapeutic Advances in Childhood Leukemia; Investigational; Childhood; ALL; Relapsed ALL; Refractory ALL; Relapsed pediatric ALL; Refractory pediatric ALL; TACL; Recurrent Pediatric ALL