Trial Outcomes & Findings for Bortezomib and Vorinostat in Treating Patients With High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia (NCT NCT00818649)

Last Updated: 2017-12-28

Results Overview

Assessed by the International Working Group response criteria: Complete Remission - \<5% myeloblasts with normal maturation of all cell lines; Partial Remission - bone marrow blasts decreased by \> 50% over pre-treatment but still \>5%; and Hematologic Improvement - hemoglobin increase by \> 1.5g/dl or decreased transfusions by at least 4/8 week period, platelet absolute increase of \>30 X 10\^9/L for those starting at \>20 X 10\^9/L . For those \< 20 X 10\^9 /L at baseline increase by 100%.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

16 participants

Primary outcome timeframe

At Completion of Course 3 (Day 63)

Results posted on

2017-12-28

Participant Flow

Study entry is open to patients regardless of gender or ethnic background.

Participant milestones

Participant milestones
Measure	Velcade + Vorinostat in MDS and AML This is a phase II two stage single arm study combining Velcade on days 1, 4, 8, and 11 plus oral Vorinostat days 1-14 of a 21 days cycle. Treatment will continue for a total of 3 treatment cycles. vorinostat : 400 mg orally (po) every day on days 1-14 of a 21 day cycle bortezomib : 1.3mg/m\^2 via peripheral subcutaneous administration on day 1, 4, 8, 11 of a 21 day cycle
Overall Study STARTED	16
Overall Study COMPLETED	12
Overall Study NOT COMPLETED	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Velcade + Vorinostat in MDS and AML This is a phase II two stage single arm study combining Velcade on days 1, 4, 8, and 11 plus oral Vorinostat days 1-14 of a 21 days cycle. Treatment will continue for a total of 3 treatment cycles. vorinostat : 400 mg orally (po) every day on days 1-14 of a 21 day cycle bortezomib : 1.3mg/m\^2 via peripheral subcutaneous administration on day 1, 4, 8, 11 of a 21 day cycle
Overall Study Declining performance status	2
Overall Study Unrelated hip fracture-unable to proceed	1
Overall Study Adverse Event	1

Baseline Characteristics

Bortezomib and Vorinostat in Treating Patients With High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Velcade + Vorinostat n=16 Participants This is a phase II two stage single arm study combining Velcade on days 1, 4, 8, and 11 plus oral Vorinostat days 1-14 of a 21 days cycle. Treatment will continue for a total of 3 treatment cycles. vorinostat : 400 mg orally (po) every day on days 1-14 of a 21 day cycle bortezomib : 1.3mg/m\^2 via peripheral subcutaneous administration on day 1, 4, 8, 11 of a 21 day cycle
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=93 Participants
Age, Categorical >=65 years	8 Participants n=93 Participants
Age, Continuous	65.5 Years n=93 Participants
Sex: Female, Male Female	8 Participants n=93 Participants
Sex: Female, Male Male	8 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	1 Participants n=93 Participants
Race (NIH/OMB) White	15 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Region of Enrollment United States	16 participants n=93 Participants

PRIMARY outcome

Timeframe: At Completion of Course 3 (Day 63)

Population: Evaluable patients are defined as those who completed at least 1 cycle of therapy; 8 had acute myeloid leukemia, 4 had myelodysplastic syndrome.

Outcome measures

Outcome measures
Measure	Evaluable Patients n=12 Participants This is a phase II two stage single arm study combining Velcade on days 1, 4, 8, and 11 plus oral Vorinostat days 1-14 of a 21 days cycle. Treatment continued for a total of 3 treatment cycles. vorinostat : 400 mg orally (po) every day on days 1-14 of a 21 day cycle bortezomib : 1.3mg/m\^2 via peripheral subcutaneous administration on day 1, 4, 8, 11 of a 21 day cycle
Number of Patients by Best Clinical Response Complete Remission	1 Patients
Number of Patients by Best Clinical Response Progressive Disease	6 Patients
Number of Patients by Best Clinical Response Stable Disease	5 Patients

SECONDARY outcome

Timeframe: Pre-Study and After 3 Cycles

Population: Natural Killer cell studies were discontinued after the first 3 patients because the results were not helpful, and thus the secondary outcome measures were not completed.

Analysis of Natural Killer (NK) Cell Activating and Inhibitory Receptor Alterations, NK Cell Receptor Ligand Alterations, HLA Class I Expression on Target Cells (Myeloid Blasts), and NK-mediated Cell Killing

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Pre-Study and After 3 Cycles

Population: Natural Killer cell studies were discontinued after the first 3 patients because the results were not helpful. So, secondary outcome measures were not completed.

Outcome measures

Outcome data not reported

Adverse Events

Velcade + Vorinostat

Serious events: 3 serious events

Other events: 15 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Velcade + Vorinostat n=16 participants at risk This is a phase II two stage single arm study combining Velcade on days 1, 4, 8, and 11 plus oral Vorinostat days 1-14 of a 21 days cycle. Treatment will continue for a total of 3 treatment cycles. vorinostat : 400 mg orally (po) every day on days 1-14 of a 21 day cycle bortezomib : 1.3mg/m\^2 via peripheral subcutaneous administration on day 1, 4, 8, 11 of a 21 day cycle
Cardiac disorders Cardiac arrest	12.5% 2/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Cardiac disorders Ischemia/Elevated Troponin	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.

Other adverse events

Other adverse events
Measure	Velcade + Vorinostat n=16 participants at risk This is a phase II two stage single arm study combining Velcade on days 1, 4, 8, and 11 plus oral Vorinostat days 1-14 of a 21 days cycle. Treatment will continue for a total of 3 treatment cycles. vorinostat : 400 mg orally (po) every day on days 1-14 of a 21 day cycle bortezomib : 1.3mg/m\^2 via peripheral subcutaneous administration on day 1, 4, 8, 11 of a 21 day cycle
Gastrointestinal disorders Abdominal pain	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Gastrointestinal disorders Anorexia	50.0% 8/16 • Number of events 9 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Gastrointestinal disorders Constipation	31.2% 5/16 • Number of events 5 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Respiratory, thoracic and mediastinal disorders Cough	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Gastrointestinal disorders Dehydration	12.5% 2/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Nervous system disorders Depression	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Gastrointestinal disorders Diarrhea	43.8% 7/16 • Number of events 11 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Eye disorders Diplopia	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Nervous system disorders Dizziness	18.8% 3/16 • Number of events 5 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Respiratory, thoracic and mediastinal disorders Dyspnea	12.5% 2/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Vascular disorders Edema	25.0% 4/16 • Number of events 4 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Investigations Elevated ALT/AST/Alkaline Phosphatase	12.5% 2/16 • Number of events 10 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Investigations Elevated creatinine	25.0% 4/16 • Number of events 10 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Eye disorders Eye pain/blurred vision	12.5% 2/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Skin and subcutaneous tissue disorders Fash rash	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
General disorders Fatigue	56.2% 9/16 • Number of events 10 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Blood and lymphatic system disorders Febrile neutropenia	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
General disorders Fever	18.8% 3/16 • Number of events 6 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Gastrointestinal disorders Gingival erythema	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Injury, poisoning and procedural complications Hip fracture	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Metabolism and nutrition disorders Hyperbilirubinemia	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Metabolism and nutrition disorders Hypoalbuminemia	12.5% 2/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Metabolism and nutrition disorders Hypoglycemia	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Metabolism and nutrition disorders Hypokalemia	18.8% 3/16 • Number of events 6 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Metabolism and nutrition disorders Hyponatremia	25.0% 4/16 • Number of events 6 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Cardiac disorders Hypotension	12.5% 2/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Respiratory, thoracic and mediastinal disorders Hypoxia	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Infections and infestations Infection, ANC=.03	6.2% 1/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Psychiatric disorders Insomnia	12.5% 2/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Musculoskeletal and connective tissue disorders Involuntary movements	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Cardiac disorders Ischemia	12.5% 2/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Musculoskeletal and connective tissue disorders Joint pain	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Gastrointestinal disorders Mucositis	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Musculoskeletal and connective tissue disorders Muscle leg pain	6.2% 1/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Musculoskeletal and connective tissue disorders Muscle weakness	12.5% 2/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Gastrointestinal disorders Nausea or vomiting	56.2% 9/16 • Number of events 17 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Nervous system disorders Neuropathy	25.0% 4/16 • Number of events 5 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Respiratory, thoracic and mediastinal disorders Nose bleeding	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Renal and urinary disorders Pain upon urination	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Respiratory, thoracic and mediastinal disorders Pulmonary infection/pneumonia	12.5% 2/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Cardiac disorders QT prolongation	37.5% 6/16 • Number of events 9 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Gastrointestinal disorders Rectal/hemorrhoidal pain	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
General disorders Shingles flare	6.2% 1/16 • Number of events 1 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Gastrointestinal disorders Small bowel obstruction	12.5% 2/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Nervous system disorders Syncope	12.5% 2/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Cardiac disorders Systolic murmur	12.5% 2/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.
Gastrointestinal disorders Tongue blister	12.5% 2/16 • Number of events 2 All patients treated on the trial were included in evaluation of toxicity. Toxicities are defined as non-hematologic given the concurrent impact of AML and MDS on cytopenias.

Additional Information

Erica Warlick, M.D.

Masonic Cancer Center, University of Minnesota

Phone: 612-625-5467

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place