Conditions: Acute Lymphoblastic Leukemia
Allocation: NA | Intervention model: SINGLE_GROUP
Enrollment: 2
Healthy volunteers: no

Brief summary:
Both of bortezomib and vorinostat have identified Phase II doses for pediatric and adult patients of which no grade 4 dose limiting toxicities have been observed in prior studies. The pre-clinical synergy of these 2 agents when used in combination along with the lack of over-riding toxicities and different mechanisms of action provide strong rationale for a clinical trial investigating bortezomib and vorinostat in combination. This trial will use the identified Phase II dose which is at or below the maximum tolerated dose for both agents which have very acceptable toxicity profiles and such should prove feasible and tolerable in this relapsed/refractory ALL population.

Detailed description:
This is a phase II study of bortezomib 1.3 mg/m\^2 by intravenous pyelogram (IVP) on days 1, 4, 8, and 11, vorinostat 180 mg/m\^2 by mouth (PO) per day (not to exceed 400 mg per day) days 1-14, and dexamethasone 6 mg/m\^2 PO days 4-15 for the treatment of relapsed/refractory acute lymphoblastic leukemia (ALL). No more than 3 treatment courses may be given.

Arms:
arm 1: Bortezomib IV Vorinostat PO Dexamethasone PO Intrathecal Methotrexate Imatinib Mesylate PO (for Ph+ ALL patients only)

Interventions: intervention 1: Bortezomib intervention 2: Vorinostat intervention 3: Dexamethasone intervention 4: Methotrexate intervention 5: Imatinib mesylate
Intervention descriptions: intervention 1: 1.3 mg/m\^2 by intravenous pyelogram (IVP) over 3-5 seconds on days 1, 4, 8 and 11. intervention 2: 180 mg/m\^2 (max dose 400mg) by mouth (PO) divided twice a day (BID) on days 1-14 intervention 3: 6 mg/m\^2 by mouth (PO) divided twice a day (BID) on days 4-15. intervention 4: Intrathecal Methotrexate at age based dose on day 1 (repeat on day 15 or 16 for CNS positive patients only) intervention 5: For Ph+ acute lymphoblastic leukemia (ALL) patients only:

Imatinib Mesylate is allowable at 340 mg/m2 PO once a day (rounded to the nearest 100 mg) for age ≤18 years and 400 mg for \>18 years on Days 1-16.

Protocol document: