Trial Outcomes & Findings for Decitabine and Vorinostat Conditioning Followed by CD3-/CD19- NK Cells Infusion for High Risk Myelodysplastic Syndromes (NCT NCT01593670)

Last Updated: 2019-05-21

Results Overview

Clinical response includes: Complete Response (less than 5% myeloblasts present in the bone marrow and in the peripheral blood a hemoglobin of at least 11g/dl, platelets of at least 100 X 10E9/L, neutrophils of at least 1.0 X 10E9/L, and blasts 0%); Partial Response (all Complete Response criteria if previously abnormal except bone marrow myeloblasts are decreased by more than 50% over pre-treatment, but still greater than 5%); and hematologic improvement (a hemoglobin increase of greater than 1.5g/dl or decreased red blood cell transfusions by at least 4 per 8 week period, a platelet increase of more than 30 X 10E9/L for patients with a baseline of more than 20 X 10E9/L or an increase by 100% for those with a baseline of less than 20 X 10E9/L, and a neutrophil increase of at least 100% and an absolute increase of greater than 0.5 X 10E9/L.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

9 participants

Primary outcome timeframe

After 2 Courses of Treatment (Approx. 3 months)

Results posted on

2019-05-21

Participant Flow

Participant milestones

Participant milestones
Measure	Patients With High Risk MDS Patients who received treatment for high risk myelodysplastic syndromes (MDS). Treatment Received: Decitabine 10 mg/m\^2/day intravenous (IV) over 1 hour days 1-5; Vorinostat 200 mg by mouth (PO) twice a day days 6-15; Il-2 activated donor natural killer cells (NK) infusion IV over 15 to 60 minutes day 17; Interleukin-2 6 million units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17. Repeat treatment course 6 to 8 weeks after cycle 1 start date. Decitabine: administered intravenous (IV), 10 mg/m\^2/day over 1 hour on days 1-5. Vorinostat: 200 mg by mouth (PO) twice a day on days 6-15 Interleukin-2: 6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17 Natural killer (NK) cells: infusion intravenously (IV) over 15 to 60 minutes day 17
Overall Study STARTED	9
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Decitabine and Vorinostat Conditioning Followed by CD3-/CD19- NK Cells Infusion for High Risk Myelodysplastic Syndromes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Patients With High Risk MDS n=9 Participants Patients who received treatment for high risk myelodysplastic syndromes (MDS). Treatment Received: Decitabine 10 mg/m\^2/day intravenous (IV) over 1 hour days 1-5; Vorinostat 200 mg by mouth (PO) twice a day days 6-15; Il-2 activated donor natural killer cells (NK) infusion IV over 15 to 60 minutes day 17; Interleukin-2 6 million units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17. Repeat treatment course 6 to 8 weeks after cycle 1 start date. Decitabine: administered intravenous (IV), 10 mg/m\^2/day over 1 hour on days 1-5. Vorinostat: 200 mg by mouth (PO) twice a day on days 6-15 Interleukin-2: 6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17 Natural killer (NK) cells: infusion intravenously (IV) over 15 to 60 minutes day 17
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	6 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants
Sex: Female, Male Female	5 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	9 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: After 2 Courses of Treatment (Approx. 3 months)

Outcome measures

Outcome measures
Measure	Patients With High Risk MDS n=9 Participants Patients who received treatment for high risk myelodysplastic syndromes (MDS). Treatment Received: Decitabine 10 mg/m\^2/day intravenous (IV) over 1 hour days 1-5; Vorinostat 200 mg by mouth (PO) twice a day days 6-15; Il-2 activated donor natural killer cells (NK) infusion IV over 15 to 60 minutes day 17; Interleukin-2 6 million units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17. Repeat treatment course 6 to 8 weeks after cycle 1 start date. Decitabine: administered intravenous (IV), 10 mg/m\^2/day over 1 hour on days 1-5. Vorinostat: 200 mg by mouth (PO) twice a day on days 6-15 Interleukin-2: 6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17 Natural killer (NK) cells: infusion intravenously (IV) over 15 to 60 minutes day 17
The Number of Patients Who Achieved a Clinical Response	5 Participants

SECONDARY outcome

Timeframe: Day 1 through Month 3

Adverse events (AEs) will be graded using Common Terminology Criteria for Adverse Events v4.0 (CTCAE). Non-hematologic adverse events are defined as untoward medical occurrences associated with the use of a study drug whether or not considered study drug related, excluding those events involving white blood cells, neutrophils, red blood cells or platelets. In general, grade 3 AEs are defined as 1) being severe or medically significant but,not immediately life-threatening; 2) requiring hospitalization or prolongation of hospitalization; 3) disabling; or 4) limiting self care activities. Grade 4 AEs are defined as 1) having life-threatening consequences; or 2) requiring urgent intervention. Grade 5 AEs are defined as causing death related to an adverse event.

Outcome measures

Outcome measures
Measure	Patients With High Risk MDS n=9 Participants Patients who received treatment for high risk myelodysplastic syndromes (MDS). Treatment Received: Decitabine 10 mg/m\^2/day intravenous (IV) over 1 hour days 1-5; Vorinostat 200 mg by mouth (PO) twice a day days 6-15; Il-2 activated donor natural killer cells (NK) infusion IV over 15 to 60 minutes day 17; Interleukin-2 6 million units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17. Repeat treatment course 6 to 8 weeks after cycle 1 start date. Decitabine: administered intravenous (IV), 10 mg/m\^2/day over 1 hour on days 1-5. Vorinostat: 200 mg by mouth (PO) twice a day on days 6-15 Interleukin-2: 6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17 Natural killer (NK) cells: infusion intravenously (IV) over 15 to 60 minutes day 17
Number of Patients Who Experienced Grade 3 or Higher Non-hematologic Adverse Events	7 Participants

SECONDARY outcome

Timeframe: 4-6 Months Post Start of Cycle 1

Population: 7 of the 9 patients were not evaluable for this outcome measure - 5 went on to stem cell transplant and 2 died before reaching the 4-6 month post start of cycle 1 milestone.This left 2 evaluable patients for the outcome measure, and thus this endpoint is not informative due to lack of evaluable patients.

Outcome measures

Outcome measures
Measure	Patients With High Risk MDS n=2 Participants Patients who received treatment for high risk myelodysplastic syndromes (MDS). Treatment Received: Decitabine 10 mg/m\^2/day intravenous (IV) over 1 hour days 1-5; Vorinostat 200 mg by mouth (PO) twice a day days 6-15; Il-2 activated donor natural killer cells (NK) infusion IV over 15 to 60 minutes day 17; Interleukin-2 6 million units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17. Repeat treatment course 6 to 8 weeks after cycle 1 start date. Decitabine: administered intravenous (IV), 10 mg/m\^2/day over 1 hour on days 1-5. Vorinostat: 200 mg by mouth (PO) twice a day on days 6-15 Interleukin-2: 6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17 Natural killer (NK) cells: infusion intravenously (IV) over 15 to 60 minutes day 17
Number of Patients Who Became Transfusion Independent	0 Participants

SECONDARY outcome

Timeframe: After Cycle 2 (approx. 3 months)

NK cell expansion is defined as the presence of donor NK cells in the recipient at Day 8 post NK cell infusion.

Outcome measures

Outcome measures
Measure	Patients With High Risk MDS n=9 Participants Patients who received treatment for high risk myelodysplastic syndromes (MDS). Treatment Received: Decitabine 10 mg/m\^2/day intravenous (IV) over 1 hour days 1-5; Vorinostat 200 mg by mouth (PO) twice a day days 6-15; Il-2 activated donor natural killer cells (NK) infusion IV over 15 to 60 minutes day 17; Interleukin-2 6 million units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17. Repeat treatment course 6 to 8 weeks after cycle 1 start date. Decitabine: administered intravenous (IV), 10 mg/m\^2/day over 1 hour on days 1-5. Vorinostat: 200 mg by mouth (PO) twice a day on days 6-15 Interleukin-2: 6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17 Natural killer (NK) cells: infusion intravenously (IV) over 15 to 60 minutes day 17
Number of Patients Who Had Natural Killer (NK) Cell Expansion	0 Participants

SECONDARY outcome

Timeframe: 1 Year

Patients alive at 1 year.

Outcome measures

Outcome measures
Measure	Patients With High Risk MDS n=9 Participants Patients who received treatment for high risk myelodysplastic syndromes (MDS). Treatment Received: Decitabine 10 mg/m\^2/day intravenous (IV) over 1 hour days 1-5; Vorinostat 200 mg by mouth (PO) twice a day days 6-15; Il-2 activated donor natural killer cells (NK) infusion IV over 15 to 60 minutes day 17; Interleukin-2 6 million units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17. Repeat treatment course 6 to 8 weeks after cycle 1 start date. Decitabine: administered intravenous (IV), 10 mg/m\^2/day over 1 hour on days 1-5. Vorinostat: 200 mg by mouth (PO) twice a day on days 6-15 Interleukin-2: 6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17 Natural killer (NK) cells: infusion intravenously (IV) over 15 to 60 minutes day 17
Overall Survival	3 Participants

Adverse Events

Patients With High Risk MDS

Serious events: 6 serious events

Other events: 9 other events

Deaths: 7 deaths

Serious adverse events

Serious adverse events
Measure	Patients With High Risk MDS n=9 participants at risk Patients who received treatment for high risk myelodysplastic syndromes (MDS). Treatment Received: Decitabine 10 mg/m\^2/day intravenous (IV) over 1 hour days 1-5; Vorinostat 200 mg by mouth (PO) twice a day days 6-15; Il-2 activated donor natural killer cells (NK) infusion IV over 15 to 60 minutes day 17; Interleukin-2 6 million units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17. Repeat treatment course 6 to 8 weeks after cycle 1 start date. Decitabine: administered intravenous (IV), 10 mg/m\^2/day over 1 hour on days 1-5. Vorinostat: 200 mg by mouth (PO) twice a day on days 6-15 Interleukin-2: 6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17 Natural killer (NK) cells: infusion intravenously (IV) over 15 to 60 minutes day 17
Vascular disorders Hypotension	11.1% 1/9 • 1 Year
Renal and urinary disorders Renal Colic	11.1% 1/9 • 1 Year
Blood and lymphatic system disorders Febrile Neutropenia	22.2% 2/9 • 1 Year
Gastrointestinal disorders Nausea	11.1% 1/9 • 1 Year
Ear and labyrinth disorders Ear Pain	11.1% 1/9 • 1 Year
Ear and labyrinth disorders Otomastoiditis	11.1% 1/9 • 1 Year
Respiratory, thoracic and mediastinal disorders Upper Respiratory Infection	11.1% 1/9 • 1 Year
Infections and infestations Infection, Source Unknown	11.1% 1/9 • 1 Year
Respiratory, thoracic and mediastinal disorders Hypoxia	11.1% 1/9 • 1 Year

Other adverse events

Other adverse events
Measure	Patients With High Risk MDS n=9 participants at risk Patients who received treatment for high risk myelodysplastic syndromes (MDS). Treatment Received: Decitabine 10 mg/m\^2/day intravenous (IV) over 1 hour days 1-5; Vorinostat 200 mg by mouth (PO) twice a day days 6-15; Il-2 activated donor natural killer cells (NK) infusion IV over 15 to 60 minutes day 17; Interleukin-2 6 million units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17. Repeat treatment course 6 to 8 weeks after cycle 1 start date. Decitabine: administered intravenous (IV), 10 mg/m\^2/day over 1 hour on days 1-5. Vorinostat: 200 mg by mouth (PO) twice a day on days 6-15 Interleukin-2: 6 million Units subcutaneous (SQ) 3 times a week for 3 doses beginning day 17 Natural killer (NK) cells: infusion intravenously (IV) over 15 to 60 minutes day 17
General disorders Chills	77.8% 7/9 • 1 Year
Respiratory, thoracic and mediastinal disorders Cough	11.1% 1/9 • 1 Year
Investigations Creatinine Increased	44.4% 4/9 • 1 Year
Respiratory, thoracic and mediastinal disorders Dyspnea	88.9% 8/9 • 1 Year
General disorders Edema, NOS	44.4% 4/9 • 1 Year
General disorders Fatigue	33.3% 3/9 • 1 Year
Blood and lymphatic system disorders Febrile Neutropenia	66.7% 6/9 • 1 Year
General disorders Fever	44.4% 4/9 • 1 Year
Nervous system disorders Headache	11.1% 1/9 • 1 Year
Vascular disorders Hypertension	66.7% 6/9 • 1 Year
Vascular disorders Hypotension	22.2% 2/9 • 1 Year
Respiratory, thoracic and mediastinal disorders Hypoxia	33.3% 3/9 • 1 Year
General disorders Infusion Related Reaction	22.2% 2/9 • 1 Year
General disorders Injection Site Reaction	66.7% 6/9 • 1 Year
Skin and subcutaneous tissue disorders Itchy Nose	11.1% 1/9 • 1 Year
Respiratory, thoracic and mediastinal disorders Nasal Drainage	11.1% 1/9 • 1 Year
Gastrointestinal disorders Nausea	11.1% 1/9 • 1 Year
Infections and infestations Para-Influenza	11.1% 1/9 • 1 Year
Skin and subcutaneous tissue disorders Pruritus	11.1% 1/9 • 1 Year
Skin and subcutaneous tissue disorders Rash	33.3% 3/9 • 1 Year
Investigations White Blood Cell Decreased	44.4% 4/9 • 1 Year
Investigations Neutrophil Count Decreased	77.8% 7/9 • 1 Year
Investigations Platelet Count Decreased	77.8% 7/9 • 1 Year
Infections and infestations Bacteremia	11.1% 1/9 • 1 Year
Infections and infestations Cellulitis, Toe	11.1% 1/9 • 1 Year
Investigations Alanine Aminotransferase Increased	11.1% 1/9 • 1 Year
Investigations Aspartate Aminotransferase Increased	22.2% 2/9 • 1 Year
Musculoskeletal and connective tissue disorders Arthralgia	11.1% 1/9 • 1 Year
Metabolism and nutrition disorders Anorexia	11.1% 1/9 • 1 Year
Investigations Blood Bilirubin Increased	11.1% 1/9 • 1 Year
Hepatobiliary disorders Cholecystitis	11.1% 1/9 • 1 Year
Investigations Cholesterol High	11.1% 1/9 • 1 Year
Gastrointestinal disorders Diarrhea	22.2% 2/9 • 1 Year
Ear and labyrinth disorders Ear Pain	11.1% 1/9 • 1 Year
Metabolism and nutrition disorders Hypocalcemia	11.1% 1/9 • 1 Year
General disorders Edema, Ankle	11.1% 1/9 • 1 Year
Musculoskeletal and connective tissue disorders Pain, Toe	11.1% 1/9 • 1 Year
Renal and urinary disorders Renal Calculi	11.1% 1/9 • 1 Year
Renal and urinary disorders Renal Colic	11.1% 1/9 • 1 Year
Infections and infestations Urinary Tract Infection	11.1% 1/9 • 1 Year

Additional Information

Dr. Erica Warlick

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