Trial Outcomes & Findings for Bortezomib, Vorinostat and Dexamethasone for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL) (NCT NCT01312818)

Last Updated: 2017-12-28

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

2 participants

Primary outcome timeframe

Day 30

Results posted on

2017-12-28

Participant Flow

Participant milestones

Participant milestones
Measure	Chemotherapy bortezomib, vorinostat and dexamethasone combination, as well as intrathecal methotrexate and imatinib mesylate. Bortezomib: 1.3 mg/m\^2 by intravenous pyelogram (IVP) over 3-5 seconds on days 1, 4, 8 and 11. Vorinostat: 180 mg/m\^2 (max dose 400mg) by mouth (PO) divided twice a day (BID) on days 1-14 Dexamethasone: 6 mg/m\^2 by mouth (PO) divided twice a day (BID) on days 4-15. Methotrexate: Intrathecal Methotrexate at age based dose on day 1 (repeat on day 15 or 16 for CNS positive patients only) 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.
Overall Study STARTED	2
Overall Study COMPLETED	2
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Bortezomib, Vorinostat and Dexamethasone for Relapsed/Refractory Acute Lymphoblastic Leukemia (ALL)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Chemotherapy n=2 Participants bortezomib, vorinostat and dexamethasone combination, as well as intrathecal methotrexate and imatinib mesylate. Bortezomib: 1.3 mg/m\^2 by intravenous pyelogram (IVP) over 3-5 seconds on days 1, 4, 8 and 11. Vorinostat: 180 mg/m\^2 (max dose 400mg) by mouth (PO) divided twice a day (BID) on days 1-14 Dexamethasone: 6 mg/m\^2 by mouth (PO) divided twice a day (BID) on days 4-15. Methotrexate: Intrathecal Methotrexate at age based dose on day 1 (repeat on day 15 or 16 for CNS positive patients only) 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.
Age, Categorical <=18 years	2 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Region of Enrollment United States	2 participants n=5 Participants

PRIMARY outcome

Timeframe: Day 30

Outcome measures

Outcome measures
Measure	ALL Treated Patients n=2 Participants bortezomib, vorinostat and dexamethasone combination, as well as intrathecal methotrexate and imatinib mesylate. Bortezomib: 1.3 mg/m\^2 by intravenous pyelogram (IVP) over 3-5 seconds on days 1, 4, 8 and 11. Vorinostat: 180 mg/m\^2 (max dose 400mg) by mouth (PO) divided twice a day (BID) on days 1-14 Dexamethasone: 6 mg/m\^2 by mouth (PO) divided twice a day (BID) on days 4-15. Methotrexate: Intrathecal Methotrexate at age based dose on day 1 (repeat on day 15 or 16 for CNS positive patients only) 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.
Number of Subjects Who Achieved Complete Remission of Their Disease	0 participants

SECONDARY outcome

Timeframe: Day 1 of Treatment to 30 Days Post Treatment

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).

Outcome measures

Outcome measures
Measure	ALL Treated Patients n=2 Participants bortezomib, vorinostat and dexamethasone combination, as well as intrathecal methotrexate and imatinib mesylate. Bortezomib: 1.3 mg/m\^2 by intravenous pyelogram (IVP) over 3-5 seconds on days 1, 4, 8 and 11. Vorinostat: 180 mg/m\^2 (max dose 400mg) by mouth (PO) divided twice a day (BID) on days 1-14 Dexamethasone: 6 mg/m\^2 by mouth (PO) divided twice a day (BID) on days 4-15. Methotrexate: Intrathecal Methotrexate at age based dose on day 1 (repeat on day 15 or 16 for CNS positive patients only) 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.
Number of Subjects Experiencing Drug Related Adverse Events	1 participants

SECONDARY outcome

Timeframe: From Day 1 to 30 Days After Last Dose

Population: The trial was terminated early with only 2 patients so caspase samples were not sent for analysis.

Activation of caspases and other regulators of apoptosis in treated blast cells will be determined by Western analysis (correlative lab analysis).

Outcome measures

Outcome data not reported

Adverse Events

Chemotherapy

Serious events: 1 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Chemotherapy n=2 participants at risk bortezomib, vorinostat and dexamethasone combination, as well as intrathecal methotrexate and imatinib mesylate. Bortezomib: 1.3 mg/m\^2 by intravenous pyelogram (IVP) over 3-5 seconds on days 1, 4, 8 and 11. Vorinostat: 180 mg/m\^2 (max dose 400mg) by mouth (PO) divided twice a day (BID) on days 1-14 Dexamethasone: 6 mg/m\^2 by mouth (PO) divided twice a day (BID) on days 4-15. Methotrexate: Intrathecal Methotrexate at age based dose on day 1 (repeat on day 15 or 16 for CNS positive patients only) 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.
Infections and infestations Sepsis	50.0% 1/2 • Number of events 1
Blood and lymphatic system disorders death from disease	50.0% 1/2 • Number of events 1
Gastrointestinal disorders esophageal ulcer	50.0% 1/2 • Number of events 1

Other adverse events

Other adverse events
Measure	Chemotherapy n=2 participants at risk bortezomib, vorinostat and dexamethasone combination, as well as intrathecal methotrexate and imatinib mesylate. Bortezomib: 1.3 mg/m\^2 by intravenous pyelogram (IVP) over 3-5 seconds on days 1, 4, 8 and 11. Vorinostat: 180 mg/m\^2 (max dose 400mg) by mouth (PO) divided twice a day (BID) on days 1-14 Dexamethasone: 6 mg/m\^2 by mouth (PO) divided twice a day (BID) on days 4-15. Methotrexate: Intrathecal Methotrexate at age based dose on day 1 (repeat on day 15 or 16 for CNS positive patients only) 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.
Metabolism and nutrition disorders Hyponatremia	50.0% 1/2 • Number of events 1
Respiratory, thoracic and mediastinal disorders Dyspnea	50.0% 1/2 • Number of events 1
Respiratory, thoracic and mediastinal disorders Hypoxia	50.0% 1/2 • Number of events 1
Respiratory, thoracic and mediastinal disorders Respiratory failure	50.0% 1/2 • Number of events 1
Gastrointestinal disorders Gastric hemorrhage	50.0% 1/2 • Number of events 1
Gastrointestinal disorders Gastric ulcer	50.0% 1/2 • Number of events 1
General disorders Fever	50.0% 1/2 • Number of events 1
Investigations Alanine aminotransferase increased	50.0% 1/2 • Number of events 1
Investigations Aspartate aminotransferase increased	50.0% 1/2 • Number of events 1
Investigations Investigations - Other, specify: hyperphosphatemia	50.0% 1/2 • Number of events 1
Vascular disorders Hypotension	50.0% 1/2 • Number of events 1

Additional Information

Dr. Michael Burke, MD

University of Minnesota, Pediatric Hematology Dept.

Phone: 612-672-7422

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place