Bortezomib, Vorinostat and Dexamethasone for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)
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.
Acute Lymphoblastic Leukemia
Drug: Imatinib mesylate
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Therapeutic Trial of Bortezomib (Velcade), Vorinostat (SAHA) and Dexamethasone for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)|
- Number of Subjects Who Achieved Complete Remission of Their Disease [ Time Frame: Day 30 ] [ Designated as safety issue: No ]Complete Remission (CR): A CR requires that the following be recorded concurrently: an absolute neutrophil count (segs and bands) > 1000/μL, no circulating blasts, platelets > 100,000/μL; adequate bone marrow cellularity with trilineage hematopoiesis, and < 5% marrow leukemia blast cells. All previous extramedullary manifestations of disease must be absent. If patients continue on with treatment, there can be no evidence of recurrence of ALL for at least 4 weeks.
- Number of Subjects Experiencing Drug Related Adverse Events [ Time Frame: Day 1 of Treatment to 30 Days Post Treatment ] [ Designated as safety issue: Yes ]To characterize the toxicities of bortezomib, vorinostat and dexamethasone when used in combination. Toxicity will be graded using the NCI's Common Terminology Criteria for Adverse Events (CTCAE 4.0).
- Number of Subjects With Activated Caspases and Other Regulators of Apoptosis [ Time Frame: From Day 1 to 30 Days After Last Dose ] [ Designated as safety issue: No ]Activation of caspases and other regulators of apoptosis in treated blast cells will be determined by Western analysis (correlative lab analysis).
|Study Start Date:||June 2011|
|Study Completion Date:||January 2013|
|Primary Completion Date:||January 2013 (Final data collection date for primary outcome measure)|
Bortezomib IV Vorinostat PO Dexamethasone PO Intrathecal Methotrexate Imatinib Mesylate PO (for Ph+ ALL patients only)
1.3 mg/m^2 by intravenous pyelogram (IVP) over 3-5 seconds on days 1, 4, 8 and 11.
Other Name: Velcade(R)Drug: Vorinostat
180 mg/m^2 (max dose 400mg) by mouth (PO) divided twice a day (BID) on days 1-14
Other Names:Drug: Dexamethasone
6 mg/m^2 by mouth (PO) divided twice a day (BID) on days 4-15.
Other Name: DecadronDrug: Methotrexate
Intrathecal Methotrexate at age based dose on day 1 (repeat on day 15 or 16 for CNS positive patients only)
Other Names:Drug: Imatinib mesylate
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.
Other Name: Gleevec(R)
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01312818
|United States, Minnesota|
|Masonic Cancer Center, University if Minnesota|
|Minneapolis, Minnesota, United States, 55455|
|Principal Investigator:||Michael Burke, MD||Masonic Cancer Center, University of Minnesota|