Trial Outcomes & Findings for Decitabine With GCLAM for Adults With Newly Diagnosed, Relapsed, or Refractory AML or High-Risk MDS (NCT NCT02921061)
NCT ID: NCT02921061
Last Updated: 2020-03-17
Results Overview
Evaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. MTD is defined as the highest dose studied in which the incidence of DLT is \< 33%. Each participant was monitored for DLTs in the first 20 days of treatment. DLTs monitored included 1. any grade 3 non-hematologic toxicity lasting more than 48 hours that resulted in more than a 7 day delay of the subsequent treatment cycle (except for febrile neutropenia or infection) 2. any grade 4 or greater non-hematologic toxicity (except febrile neutropenia and infection unless a direct consequence of a treatment-related toxicity, and except constitutional symptoms if they recovered to grade 2 or less within 14 days) 3. lack of recovery of the absolute neutrophil count to 500/microliter or greater and lack of self-sustained platelet count of at least 50,000/microliter by treatment day +49 with no evidence of residual leukemia
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
28 participants
Primary outcome timeframe
Up to 49 days
Results posted on
2020-03-17
Participant Flow
Though this is a dose escalation study, all patients ultimately received decitabine at the same dose (20 mg/m2) and the same additional drugs (G-CLAM) over the same dosing schedule.
Participant milestones
| Measure |
Treatment (Decitabine 20 mg/m2 and G-CLAM)
Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3).
Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM.
Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
|
|---|---|
|
Overall Study
STARTED
|
28
|
|
Overall Study
COMPLETED
|
28
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Decitabine With GCLAM for Adults With Newly Diagnosed, Relapsed, or Refractory AML or High-Risk MDS
Baseline characteristics by cohort
| Measure |
Treatment (Decitabine 20 mg/m2 and G-CLAM)
n=28 Participants
Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3).
Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM.
Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
|
|---|---|
|
Age, Continuous
|
67 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
10 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
18 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
26 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
3 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
|
25 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: Up to 49 daysEvaluated according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. MTD is defined as the highest dose studied in which the incidence of DLT is \< 33%. Each participant was monitored for DLTs in the first 20 days of treatment. DLTs monitored included 1. any grade 3 non-hematologic toxicity lasting more than 48 hours that resulted in more than a 7 day delay of the subsequent treatment cycle (except for febrile neutropenia or infection) 2. any grade 4 or greater non-hematologic toxicity (except febrile neutropenia and infection unless a direct consequence of a treatment-related toxicity, and except constitutional symptoms if they recovered to grade 2 or less within 14 days) 3. lack of recovery of the absolute neutrophil count to 500/microliter or greater and lack of self-sustained platelet count of at least 50,000/microliter by treatment day +49 with no evidence of residual leukemia
Outcome measures
| Measure |
Treatment (Decitabine 20 mg/m2 and G-CLAM)
n=28 Participants
Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3).
Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM.
Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
|
|---|---|
|
Number of Participants Experiencing Dose Limiting Toxicities (DLTs) at the Maximum Tolerated Dose (MTD) for Decitabine When Given Together With G-CLAM Toxicities (DLTs) (Phase I)
|
3 Participants
|
SECONDARY outcome
Timeframe: Up to 1 yearCompared to historical controls of filgrastim, cladribine, cytarabine, and mitoxantrone hydrochloride (G-CLAM) alone. A Simon Minimax two-stage design will be used.
Outcome measures
| Measure |
Treatment (Decitabine 20 mg/m2 and G-CLAM)
n=28 Participants
Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3).
Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM.
Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
|
|---|---|
|
Number of Participants With Minimal Residual Disease Negative (MRDneg) Complete Remission (Phase II)
|
13 participants
|
SECONDARY outcome
Timeframe: Up to 1 yearOutcome measures
| Measure |
Treatment (Decitabine 20 mg/m2 and G-CLAM)
n=28 Participants
Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3).
Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM.
Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
|
|---|---|
|
Number of Participants Who Achieved Remission (Complete Remission [CR]/CR With Incomplete Peripheral Blood Count Recovery [CRi])
|
13 participants
|
SECONDARY outcome
Timeframe: Up to 1 yearOutcome measures
| Measure |
Treatment (Decitabine 20 mg/m2 and G-CLAM)
n=28 Participants
Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3).
Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM.
Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
|
|---|---|
|
Number of Participants With Overall Survival
|
9 participants
|
SECONDARY outcome
Timeframe: Up to 1 yearOutcome measures
| Measure |
Treatment (Decitabine 20 mg/m2 and G-CLAM)
n=28 Participants
Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3).
Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM.
Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
|
|---|---|
|
Number of Participants With Relapse-free Survival
|
8 participants
|
SECONDARY outcome
Timeframe: Up to 1 yearOutcome measures
| Measure |
Treatment (Decitabine 20 mg/m2 and G-CLAM)
n=28 Participants
Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3).
Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM.
Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
|
|---|---|
|
Number of Participants With Event-free Survival
|
8 participants
|
Adverse Events
Treatment (Decitabine 20 mg/m2 and G-CLAM)
Serious events: 2 serious events
Other events: 28 other events
Deaths: 19 deaths
Serious adverse events
| Measure |
Treatment (Decitabine 20 mg/m2 and G-CLAM)
n=28 participants at risk
Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3).
Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM.
Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
|
|---|---|
|
Infections and infestations
Sepsis
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Cardiac disorders
Cardiogenic shock/heart failure
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
Other adverse events
| Measure |
Treatment (Decitabine 20 mg/m2 and G-CLAM)
n=28 participants at risk
Patients receive induction therapy comprising decitabine IV over 1 hour (20 mg/m2) on days 1-10 and G-CLAM (filgrastim SC on days 0-5, cladribine IV over 2 hours on days 1-5, cytarabine IV over 2-4 hours on days 1-5, and mitoxantrone IV over 60 minutes on days 1-3).
Patients who do not achieve MRDneg CR after first induction are eligible for re-induction with G-CLAM.
Beginning 6 weeks after achieving MRDneg CR or CR/CR with CRi after induction and/or re-induction, patients are eligible to receive consolidation therapy comprising GLCA (filgrastim, cladribine, cytarabine) for up to 4 cycles. Subsequent consolidation cycles would be given after recovery from the previous cycle (roughly 4-6 weeks).
|
|---|---|
|
Renal and urinary disorders
acute kidney injury, grade 3
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Cardiac disorders
aortic valve disease, grade 3
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Hepatobiliary disorders
AST increased, grade 3
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Cardiac disorders
atrial fibrillation, grade 3
|
7.1%
2/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Cardiac disorders
atrial fibrillation, grade 4
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
General disorders
back pain, grade 3
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Psychiatric disorders
delirium, grade 3
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Gastrointestinal disorders
diarrhea, grade 3
|
7.1%
2/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Gastrointestinal disorders
duodenal hemorrhage, grade 4
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Respiratory, thoracic and mediastinal disorders
dyspnea, grade 4
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
encephalopathy, grade 4
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
General disorders
fatigue, grade 3
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Infections and infestations
febrile neutropenia, grade 3
|
96.4%
27/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Blood and lymphatic system disorders
hyperbilirubinemia, grade 4
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
General disorders
hypertension, grade 3
|
7.1%
2/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Metabolism and nutrition disorders
hypokalemia, grade 3
|
7.1%
2/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
General disorders
hypotension, grade 3
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
General disorders
hypoxemia, grade 3
|
25.0%
7/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Cardiac disorders
infective endocarditis, grade 3
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
General disorders
LV systolic dysfunction, grade 4
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Skin and subcutaneous tissue disorders
maculopapular rash, grade 3
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Cardiac disorders
myocardial infarction, grade 4
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
General disorders
nausea, grade 3
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Vascular disorders
phlebitis infective, grade 3
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Respiratory, thoracic and mediastinal disorders
pleural effusions, grade 3
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
Respiratory, thoracic and mediastinal disorders
pulmonary nodules, grade 3
|
25.0%
7/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
General disorders
sinusitis, grade 3
|
3.6%
1/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
General disorders
syncope, grade 3
|
10.7%
3/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
|
General disorders
tumor lysis syndrome, grade 3
|
7.1%
2/28 • All-Cause Mortality assessed for up to 12 months; Serious and Other Adverse Events assessed for up to 1 month after treatment duration of about 10 days concluded
|
Additional Information
Roland B. Walter
Fred Hutchinson Cancer Research Center
Phone: 1-206-667-3599
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place