Trial Outcomes & Findings for Pevonedistat and Azacitidine as Maintenance Therapy After Allogeneic Stem Cell Transplantation for Non-Remission AML (NCT NCT03709576)
NCT ID: NCT03709576
Last Updated: 2020-12-16
Results Overview
One year overall survival assess by Kaplan Meier Plots
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
3 participants
Primary outcome timeframe
1 year
Results posted on
2020-12-16
Participant Flow
Subjects were recruited from the Penn State Milton S. Hershey Medical Center from 18 July 2018 through 17 October 2019
One subject was excluded due to progression of disease prior to enrollment
Participant milestones
| Measure |
Pevonedistat and Azacitidine
The study period is from the start of study treatment, cycle 1 day 1 until 28 days after the last treatment dose. (Cycle 5 day 9). Treatment will be continued until cycle 5 is completed or the study is terminated for the patient. The cycles will be repeated every 28 days. Cycle 1 Day 1 of study treatment will be between day +30 and day +45 post-transplant. Each 28-day cycle is comprised of Pevonedistat at 20 mg/m2 IV infusion over 1 hour on days 1, 3 and 5 and Azacitidine at 25 mg/m2 IV infusion over 30 minutes on days 1, 2, 3, 4, 5, 8 and 9. The drugs can be administered either through a central catheter or a peripheral line.
Pevonedistat: To assess the toxicity and efficacy of a combination of Pevonedistat and Azacitidine as post allogeneic hematopoietic stem cell transplant maintenance therapy for non-remission AML.
transplant: Although hematopoietic stem cell transplantation (HSCT) is curative for many patients with AML, AML in relapse at the time of transplant is still a
|
|---|---|
|
Overall Study
STARTED
|
3
|
|
Overall Study
COMPLETED
|
2
|
|
Overall Study
NOT COMPLETED
|
1
|
Reasons for withdrawal
| Measure |
Pevonedistat and Azacitidine
The study period is from the start of study treatment, cycle 1 day 1 until 28 days after the last treatment dose. (Cycle 5 day 9). Treatment will be continued until cycle 5 is completed or the study is terminated for the patient. The cycles will be repeated every 28 days. Cycle 1 Day 1 of study treatment will be between day +30 and day +45 post-transplant. Each 28-day cycle is comprised of Pevonedistat at 20 mg/m2 IV infusion over 1 hour on days 1, 3 and 5 and Azacitidine at 25 mg/m2 IV infusion over 30 minutes on days 1, 2, 3, 4, 5, 8 and 9. The drugs can be administered either through a central catheter or a peripheral line.
Pevonedistat: To assess the toxicity and efficacy of a combination of Pevonedistat and Azacitidine as post allogeneic hematopoietic stem cell transplant maintenance therapy for non-remission AML.
transplant: Although hematopoietic stem cell transplantation (HSCT) is curative for many patients with AML, AML in relapse at the time of transplant is still a
|
|---|---|
|
Overall Study
progression prior to enrollment
|
1
|
Baseline Characteristics
Pevonedistat and Azacitidine as Maintenance Therapy After Allogeneic Stem Cell Transplantation for Non-Remission AML
Baseline characteristics by cohort
| Measure |
Pevonedistat and Azacitidine
n=3 Participants
The study period is from the start of study treatment, cycle 1 day 1 until 28 days after the last treatment dose. (Cycle 5 day 9). Treatment will be continued until cycle 5 is completed or the study is terminated for the patient. The cycles will be repeated every 28 days. Cycle 1 Day 1 of study treatment will be between day +30 and day +45 post-transplant. Each 28-day cycle is comprised of Pevonedistat at 20 mg/m2 IV infusion over 1 hour on days 1, 3 and 5 and Azacitidine at 25 mg/m2 IV infusion over 30 minutes on days 1, 2, 3, 4, 5, 8 and 9.
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
3 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
54 years
STANDARD_DEVIATION 4.9 • n=5 Participants
|
|
Sex/Gender, Customized
|
3 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 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
|
2 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
|
|
Region of Enrollment
United States
|
3 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 1 yearPopulation: Data could not be reported in the data table as the data were not collected due to study early termination.
One year overall survival assess by Kaplan Meier Plots
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: not analyzedPopulation: Data could not be reported in the data table as the data were not collected due to study early termination.
Toxicity and efficacy unable to be determined as trial was closed by the sponsor prior to meeting this objective.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: not analyzedPopulation: Data could not be reported in the data table as the data were not collected due to study early termination.
Toxicity related to Pevonedistat unable to be determined as trial was closed by sponsor prior to meeting this objective
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: not analyzedPopulation: Data could not be reported in the data table as the data were not collected due to study early termination.
overall disease free survival, relapse and GVHD unable to be determined as trial was closed by the sponsor prior to meeting this objective
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: not analyzedPopulation: Data could not be reported in the data table as the data were not collected due to study early termination.
One-year disease-free survival unable to be determined as trail was closed by the sponsor prior to meeting this endpoint
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: not analyzedPopulation: Data could not be reported in the data table as the data were not collected due to study early termination.
Cumulative incidence of relapse at 2 years unable to be determined as trial was closed by the sponsor prior to meeting this objective
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: not analyzedPopulation: Data could not be reported in the data table as the data were not collected due to study early termination.
Two-year and five-year disease-free and overall survival unable to be determined as trial was closed by the sponsor prior to meeting this objective
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: not analyzedPopulation: Data could not be reported in the data table as the data were not collected due to study early termination.
Treatment related mortality/morbidity unable to be determined as trial was closed by sponsor prior to meeting this objective
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: not analyzedPopulation: Data could not be reported in the data table as the data were not collected due to study early termination.
Incidence and severity of acute and chronic GVHD unable to be determined as trial was closed by sponsor prior to meeting this objective
Outcome measures
Outcome data not reported
Adverse Events
Pevonedistat and Azacitidine
Serious events: 1 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pevonedistat and Azacitidine
n=2 participants at risk
The study period is from the start of study treatment, cycle 1 day 1 until 28 days after the last treatment dose. (Cycle 5 day 9). Treatment will be continued until cycle 5 is completed or the study is terminated for the patient. The cycles will be repeated every 28 days. Cycle 1 Day 1 of study treatment will be between day +30 and day +45 post-transplant. Each 28-day cycle is comprised of Pevonedistat at 20 mg/m2 IV infusion over 1 hour on days 1, 3 and 5 and Azacitidine at 25 mg/m2 IV infusion over 30 minutes on days 1, 2, 3, 4, 5, 8 and 9.
|
|---|---|
|
Renal and urinary disorders
Acute Kidney Injury
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Infections and infestations
Sepsis
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Respiratory, thoracic and mediastinal disorders
Lung Infection
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
Other adverse events
| Measure |
Pevonedistat and Azacitidine
n=2 participants at risk
The study period is from the start of study treatment, cycle 1 day 1 until 28 days after the last treatment dose. (Cycle 5 day 9). Treatment will be continued until cycle 5 is completed or the study is terminated for the patient. The cycles will be repeated every 28 days. Cycle 1 Day 1 of study treatment will be between day +30 and day +45 post-transplant. Each 28-day cycle is comprised of Pevonedistat at 20 mg/m2 IV infusion over 1 hour on days 1, 3 and 5 and Azacitidine at 25 mg/m2 IV infusion over 30 minutes on days 1, 2, 3, 4, 5, 8 and 9.
|
|---|---|
|
Gastrointestinal disorders
abdominal pain
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
activated partial thromboplastin
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Alanine aminotransferase increased
|
100.0%
2/2 • Number of events 3 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Alkaline phosphatase increased
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Blood and lymphatic system disorders
anemia
|
100.0%
2/2 • Number of events 15 • completion of Cycle 5 day 9, up to 1 year.
|
|
General disorders
anorexia
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Aspartate aminotransferase increased
|
100.0%
2/2 • Number of events 3 • completion of Cycle 5 day 9, up to 1 year.
|
|
General disorders
Back pain
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Gastrointestinal disorders
Bloating
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Blood and lymphatic system disorders
Blood and lymphatic system disorder
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Blood lactate dehydrogenase increased
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
General disorders
Bruising
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Skin and subcutaneous tissue disorders
Bullous dermatitis
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Gastrointestinal disorders
Constipation
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Creatinine increased
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Infections and infestations
Cytomegalovirus infection reactivation
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
General disorders
Dizziness
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Gastrointestinal disorders
Dry mouth
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Gastrointestinal disorders
Dyspepsia
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Gastrointestinal disorders
Dysphasia
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Renal and urinary disorders
Dysuria
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
General disorders
Edema face
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
General disorders
Edema limbs
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
General disorders
Edema trunk
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Cardiac disorders
Ejection fraction decreased
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
General disorders
Fatigue
|
100.0%
2/2 • Number of events 3 • completion of Cycle 5 day 9, up to 1 year.
|
|
Gastrointestinal disorders
Fecal incontinence
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
General disorders
Fever
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Renal and urinary disorders
Flank pain
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Nervous system disorders
Gait disturbance
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Musculoskeletal and connective tissue disorders
Generalized muscle weakness
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Nervous system disorders
Headache
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Skin and subcutaneous tissue disorders
Hematoma
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Hyperglycemia
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Hyperkalemia
|
100.0%
2/2 • Number of events 4 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Hypermagnesemia
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Hypernatremia
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Hyperphosphatemia
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Cardiac disorders
Hypertension
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Hyperuricemia
|
100.0%
2/2 • Number of events 3 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Hypoalbuminemia
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Hypocalcemia
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Hyponatremia
|
100.0%
2/2 • Number of events 4 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Hypophosphatemia
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Cardiac disorders
Hypotension
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Blood and lymphatic system disorders
INR increased
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Investigations
Lipase increased
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Cardiac disorders
Localized edema
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Respiratory, thoracic and mediastinal disorders
Lung infection
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Blood and lymphatic system disorders
Lymphocyte count decreased
|
100.0%
2/2 • Number of events 16 • completion of Cycle 5 day 9, up to 1 year.
|
|
General disorders
Nail discoloration
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Gastrointestinal disorders
Nausea
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
General disorders
Neck edema
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Blood and lymphatic system disorders
Neutrophil count decreased
|
100.0%
2/2 • Number of events 19 • completion of Cycle 5 day 9, up to 1 year.
|
|
Blood and lymphatic system disorders
Platelet count decreased
|
100.0%
2/2 • Number of events 6 • completion of Cycle 5 day 9, up to 1 year.
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
General disorders
Pruritus
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary edema
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory failure
|
50.0%
1/2 • Number of events 3 • completion of Cycle 5 day 9, up to 1 year.
|
|
Infections and infestations
Sepsis
|
50.0%
1/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Nervous system disorders
Presyncope
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Blood and lymphatic system disorders
Sinus tachycardia
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Skin and subcutaneous tissue disorders
Skin hyperpigmentation
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Nervous system disorders
Tremor
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Infections and infestations
Urinary tract infection
|
100.0%
2/2 • Number of events 2 • completion of Cycle 5 day 9, up to 1 year.
|
|
Renal and urinary disorders
Urine discoloration
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Gastrointestinal disorders
Vomiting
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
General disorders
Weight loss
|
50.0%
1/2 • Number of events 1 • completion of Cycle 5 day 9, up to 1 year.
|
|
Blood and lymphatic system disorders
White blood cell decreased
|
100.0%
2/2 • Number of events 18 • completion of Cycle 5 day 9, up to 1 year.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place