Trial Outcomes & Findings for Study of Decitabine in Combination With Sequential Rapamycin or Ribavirin in High Risk AML Patients (NCT NCT02109744)
NCT ID: NCT02109744
Last Updated: 2022-07-05
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
27 participants
Primary outcome timeframe
2 years
Results posted on
2022-07-05
Participant Flow
37 patients signed consent for the study and 27 patients enrolled. Reasons for non-enrollment were withdrawal of consent (3 patients), diagnosis of MDS vs. AML on screening marrow (2 patients), enrollment on an alternate clinical trial (4 patients), and expiration during screening period due to sepsis (1 patient). The first patient enrolled in March 2014 and the last in January 2020.
Participant milestones
| Measure |
Decitabine Followed by Rapamycin
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Rapamycin 6mg (loading dose) will be administered on day 6; thereafter 2 mg/day on days 11-22 in cycle 1 and on days 6-22 in subsequent cycles. (Arm A: for patients with non-morphologic M4/M5 subtypes).
Decitabine
|
Decitabine Followed by Ribavirin
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Ribavirin will be dosed from day 11-day 28 beginning with dose level 1 (1000mg orally twice daily). Number of patients with Dose Limiting Toxicities (DLT) at a given dose level is 0 of out of 3: enter 3 patients at the next dose level (dose Level 2- 1200mg orally twice daily; and then dose Level 3-1400 mg orally twice daily).(Arm B: For patients with morphologic M4/M5 subtypes).
Decitabine
|
|---|---|---|
|
Overall Study
STARTED
|
26
|
1
|
|
Overall Study
COMPLETED
|
24
|
0
|
|
Overall Study
NOT COMPLETED
|
2
|
1
|
Reasons for withdrawal
| Measure |
Decitabine Followed by Rapamycin
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Rapamycin 6mg (loading dose) will be administered on day 6; thereafter 2 mg/day on days 11-22 in cycle 1 and on days 6-22 in subsequent cycles. (Arm A: for patients with non-morphologic M4/M5 subtypes).
Decitabine
|
Decitabine Followed by Ribavirin
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Ribavirin will be dosed from day 11-day 28 beginning with dose level 1 (1000mg orally twice daily). Number of patients with Dose Limiting Toxicities (DLT) at a given dose level is 0 of out of 3: enter 3 patients at the next dose level (dose Level 2- 1200mg orally twice daily; and then dose Level 3-1400 mg orally twice daily).(Arm B: For patients with morphologic M4/M5 subtypes).
Decitabine
|
|---|---|---|
|
Overall Study
Death
|
1
|
1
|
|
Overall Study
no marrow exam
|
1
|
0
|
Baseline Characteristics
Study of Decitabine in Combination With Sequential Rapamycin or Ribavirin in High Risk AML Patients
Baseline characteristics by cohort
| Measure |
Decitabine Followed by Rapamycin
n=26 Participants
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Rapamycin 6mg (loading dose) will be administered on day 6; thereafter 2 mg/day on days 11-22 in cycle 1 and on days 6-22 in subsequent cycles. (Arm A: for patients with non-morphologic M4/M5 subtypes).
Decitabine
|
Decitabine Followed by Ribavirin
n=1 Participants
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Ribavirin will be dosed from day 11-day 28 beginning with dose level 1 (1000mg orally twice daily). Number of patients with Dose Limiting Toxicities (DLT) at a given dose level is 0 of out of 3: enter 3 patients at the next dose level (dose Level 2- 1200mg orally twice daily; and then dose Level 3-1400 mg orally twice daily).(Arm B: For patients with morphologic M4/M5 subtypes).
Decitabine
|
Total
n=27 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
74 years
n=5 Participants
|
80 years
n=7 Participants
|
74 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
15 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
15 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
12 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
25 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
25 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
26 participants
n=5 Participants
|
1 participants
n=7 Participants
|
27 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 2 yearsPopulation: The Ribavirin arm did not complete the study and entered hospice before 4 weeks. Median survival of the rapamycin arm included all 26 participant who started the study.
Outcome measures
| Measure |
Decitabine Followed by Rapamycin
n=26 Participants
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Rapamycin 6mg (loading dose) will be administered on day 6; thereafter 2 mg/day on days 11-22 in cycle 1 and on days 6-22 in subsequent cycles. (Arm A: for patients with non-morphologic M4/M5 subtypes).
Decitabine
|
Decitabine Followed by Ribavirin
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Ribavirin will be dosed from day 11-day 28 beginning with dose level 1 (1000mg orally twice daily). Number of patients with Dose Limiting Toxicities (DLT) at a given dose level is 0 of out of 3: enter 3 patients at the next dose level (dose Level 2- 1200mg orally twice daily; and then dose Level 3-1400 mg orally twice daily).(Arm B: For patients with morphologic M4/M5 subtypes).
Decitabine
|
|---|---|---|
|
Median Overall Survival
|
6.9 months
Interval 4.8 to 12.2
|
—
|
SECONDARY outcome
Timeframe: baseline and four weeksPopulation: Data was not collected for two patients in the rapamycin arm and 1 patient in the ribavirin arm.
bone marrow aspirate and biopsy exam
Outcome measures
| Measure |
Decitabine Followed by Rapamycin
n=24 Participants
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Rapamycin 6mg (loading dose) will be administered on day 6; thereafter 2 mg/day on days 11-22 in cycle 1 and on days 6-22 in subsequent cycles. (Arm A: for patients with non-morphologic M4/M5 subtypes).
Decitabine
|
Decitabine Followed by Ribavirin
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Ribavirin will be dosed from day 11-day 28 beginning with dose level 1 (1000mg orally twice daily). Number of patients with Dose Limiting Toxicities (DLT) at a given dose level is 0 of out of 3: enter 3 patients at the next dose level (dose Level 2- 1200mg orally twice daily; and then dose Level 3-1400 mg orally twice daily).(Arm B: For patients with morphologic M4/M5 subtypes).
Decitabine
|
|---|---|---|
|
Blast Percentage in Peripheral Blood
baseline
|
24.7 percentage of cells
Standard Deviation 5.9
|
—
|
|
Blast Percentage in Peripheral Blood
week 4
|
14.7 percentage of cells
Standard Deviation 5.6
|
—
|
SECONDARY outcome
Timeframe: baseline and four weeksPopulation: Data was not collected for two patients in the rapamycin arm and 1 patient in the ribavirin arm.
Complete blood count with differential.
Outcome measures
| Measure |
Decitabine Followed by Rapamycin
n=24 Participants
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Rapamycin 6mg (loading dose) will be administered on day 6; thereafter 2 mg/day on days 11-22 in cycle 1 and on days 6-22 in subsequent cycles. (Arm A: for patients with non-morphologic M4/M5 subtypes).
Decitabine
|
Decitabine Followed by Ribavirin
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Ribavirin will be dosed from day 11-day 28 beginning with dose level 1 (1000mg orally twice daily). Number of patients with Dose Limiting Toxicities (DLT) at a given dose level is 0 of out of 3: enter 3 patients at the next dose level (dose Level 2- 1200mg orally twice daily; and then dose Level 3-1400 mg orally twice daily).(Arm B: For patients with morphologic M4/M5 subtypes).
Decitabine
|
|---|---|---|
|
Mean Change in Blast Percentage in Marrow
|
-18.5 percentage of cells
Interval -86.0 to 64.0
|
—
|
Adverse Events
Decitabine Followed by Rapamycin
Serious events: 21 serious events
Other events: 26 other events
Deaths: 25 deaths
Decitabine Followed by Ribavirin
Serious events: 1 serious events
Other events: 1 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Decitabine Followed by Rapamycin
n=26 participants at risk
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Rapamycin 6mg (loading dose) will be administered on day 6; thereafter 2 mg/day on days 11-22 in cycle 1 and on days 6-22 in subsequent cycles. (Arm A: for patients with non-morphologic M4/M5 subtypes).
Decitabine
|
Decitabine Followed by Ribavirin
n=1 participants at risk
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Ribavirin will be dosed from day 11-day 28 beginning with dose level 1 (1000mg orally twice daily). Number of patients with Dose Limiting Toxicities (DLT) at a given dose level is 0 of out of 3: enter 3 patients at the next dose level (dose Level 2- 1200mg orally twice daily; and then dose Level 3-1400 mg orally twice daily).(Arm B: For patients with morphologic M4/M5 subtypes).
Decitabine
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Hemoptysis
|
3.8%
1/26 • 2 years
|
100.0%
1/1 • 2 years
|
|
Infections and infestations
pneumonia
|
0.00%
0/26 • 2 years
|
100.0%
1/1 • 2 years
|
|
Nervous system disorders
syncope
|
0.00%
0/26 • 2 years
|
100.0%
1/1 • 2 years
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
42.3%
11/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Nervous system disorders
Intracranial hemorrhage
|
11.5%
3/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Gastrointestinal disorders
Gastric hemorrhage
|
3.8%
1/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Blood and lymphatic system disorders
decreased platelet count
|
3.8%
1/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Infections and infestations
skin infection
|
3.8%
1/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Infections and infestations
Sepsis
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
General disorders
Chest pain
|
3.8%
1/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Metabolism and nutrition disorders
Failure to thrive
|
3.8%
1/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Gastrointestinal disorders
Diverticulitis
|
3.8%
1/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Blood and lymphatic system disorders
Anemia
|
3.8%
1/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Mucositis
|
3.8%
1/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
General disorders
Multi-organ failure
|
3.8%
1/26 • 2 years
|
0.00%
0/1 • 2 years
|
Other adverse events
| Measure |
Decitabine Followed by Rapamycin
n=26 participants at risk
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Rapamycin 6mg (loading dose) will be administered on day 6; thereafter 2 mg/day on days 11-22 in cycle 1 and on days 6-22 in subsequent cycles. (Arm A: for patients with non-morphologic M4/M5 subtypes).
Decitabine
|
Decitabine Followed by Ribavirin
n=1 participants at risk
Decitabine 20 mg/M2/day will be given as an IV infusion daily for 10 consecutive days starting on day 1 of cycle 1; in subsequent cycles, decitabine will be given for five days (days 1-5). Ribavirin will be dosed from day 11-day 28 beginning with dose level 1 (1000mg orally twice daily). Number of patients with Dose Limiting Toxicities (DLT) at a given dose level is 0 of out of 3: enter 3 patients at the next dose level (dose Level 2- 1200mg orally twice daily; and then dose Level 3-1400 mg orally twice daily).(Arm B: For patients with morphologic M4/M5 subtypes).
Decitabine
|
|---|---|---|
|
Hepatobiliary disorders
alkaline phosphatase increased
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Metabolism and nutrition disorders
Anorexia
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Investigations
Aspartate aminotransferase increased
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Psychiatric disorders
Confusion
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Injury, poisoning and procedural complications
Fall
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Psychiatric disorders
Hallucinations
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Vascular disorders
Hypertension
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Infections and infestations
Infection
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Nervous system disorders
Lethargy
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Nervous system disorders
Peripheral Neuropathy
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Nervous system disorders
Presyncope
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Skin and subcutaneous tissue disorders
Pruritis
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Skin and subcutaneous tissue disorders
Rash
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Infections and infestations
Rhinitis/sinusitis
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Cardiac disorders
Sinus tachycardia
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Vascular disorders
Thromboembolic event
|
7.7%
2/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
General disorders
Fatigue
|
61.5%
16/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
46.2%
12/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Gastrointestinal disorders
Nausea
|
38.5%
10/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Gastrointestinal disorders
Constipation
|
34.6%
9/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
General disorders
Edema
|
26.9%
7/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
23.1%
6/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Nervous system disorders
Headache
|
23.1%
6/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Gastrointestinal disorders
Abdominal pain
|
19.2%
5/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Gastrointestinal disorders
Diarrhea
|
19.2%
5/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
General disorders
Fever
|
19.2%
5/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Vascular disorders
Hypotension
|
19.2%
5/26 • 2 years
|
100.0%
1/1 • 2 years
|
|
Infections and infestations
Skin infection
|
19.2%
5/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
15.4%
4/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Injury, poisoning and procedural complications
Bruising
|
15.4%
4/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
General disorders
Chills
|
15.4%
4/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
15.4%
4/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Gastrointestinal disorders
GI discomfort
|
15.4%
4/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Gastrointestinal disorders
Oral pain
|
15.4%
4/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Gastrointestinal disorders
Vomiting
|
15.4%
4/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Hepatobiliary disorders
ALT increased
|
11.5%
3/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Nervous system disorders
Anxiety
|
11.5%
3/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Back pain
|
11.5%
3/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Nervous system disorders
Dizziness
|
11.5%
3/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Blood and lymphatic system disorders
Bleeding from central line
|
11.5%
3/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Musculoskeletal and connective tissue disorders
Extremity pain
|
11.5%
3/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Gastrointestinal disorders
Hemorrhoids
|
11.5%
3/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Metabolism and nutrition disorders
Hypocalcemia
|
11.5%
3/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Metabolism and nutrition disorders
Hypokalemia
|
11.5%
3/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
General disorders
Malaise
|
11.5%
3/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Gastrointestinal disorders
Sore throat
|
11.5%
3/26 • 2 years
|
0.00%
0/1 • 2 years
|
|
Blood and lymphatic system disorders
Decreased platelets
|
0.00%
0/26 • 2 years
|
100.0%
1/1 • 2 years
|
|
General disorders
Pain
|
0.00%
0/26 • 2 years
|
100.0%
1/1 • 2 years
|
|
Immune system disorders
Sepsis
|
0.00%
0/26 • 2 years
|
100.0%
1/1 • 2 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place