Trial Outcomes & Findings for Clofarabine and Cytarabine in Treating Older Patients With AML or High-Risk MDS (NCT NCT00839982)
NCT ID: NCT00839982
Last Updated: 2017-07-11
Results Overview
Dose limiting toxicity (DLT) consists of grade 3-4 non-hematologic toxicity at least possibly related to study drug. Exceptions include neutropenic fever; drug-related fever; alopecia; anorexia; inadequately treated nausea, vomiting and/or diarrhea; and grade 3/4 increase in ALT, AST, or bilirubin recovering to \< grade 2 by 7 days. Prolonged grade 2 myelosuppression lasting longer than 49 days in patients who don't proceed to additional cytotoxic therapy is considered a DLT. The MTD or recommended phase II dose is the highest dose level at which no more than 1 patient out of 6 experiences DLT.
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
35 participants
Primary outcome timeframe
Outcomes by day 30
Results posted on
2017-07-11
Participant Flow
Participant milestones
| Measure |
Dose Level 1
Patients receive clofarabine 10mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 2
Patients receive clofarabine 20mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 3
Patients receive clofarabine 25mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 4
Patients receive clofarabine 30mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
4
|
26
|
2
|
3
|
|
Overall Study
COMPLETED
|
4
|
26
|
2
|
3
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Clofarabine and Cytarabine in Treating Older Patients With AML or High-Risk MDS
Baseline characteristics by cohort
| Measure |
Treatment (Chemotherapy)
n=35 Participants
Patients receive clofarabine PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
|---|---|
|
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
|
32 Participants
n=5 Participants
|
|
Age, Continuous
|
72 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
24 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
35 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Outcomes by day 30Dose limiting toxicity (DLT) consists of grade 3-4 non-hematologic toxicity at least possibly related to study drug. Exceptions include neutropenic fever; drug-related fever; alopecia; anorexia; inadequately treated nausea, vomiting and/or diarrhea; and grade 3/4 increase in ALT, AST, or bilirubin recovering to \< grade 2 by 7 days. Prolonged grade 2 myelosuppression lasting longer than 49 days in patients who don't proceed to additional cytotoxic therapy is considered a DLT. The MTD or recommended phase II dose is the highest dose level at which no more than 1 patient out of 6 experiences DLT.
Outcome measures
| Measure |
Dose Level 1
n=4 Participants
Patients receive clofarabine 10 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 2
n=26 Participants
Patients receive clofarabine 20 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 3
n=2 Participants
Patients receive clofarabine 25 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 4
n=3 Participants
Patients receive clofarabine 30 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
|---|---|---|---|---|
|
Number of Patients With Dose Limiting Toxicity
|
0 Participants
|
4 Participants
|
2 Participants
|
2 Participants
|
PRIMARY outcome
Timeframe: up to 5 yearsWe identified 20 mg/d for 5 d as the maximum tolerated dose (MTD) of oral clofarabine.
Outcome measures
| Measure |
Dose Level 1
n=35 Participants
Patients receive clofarabine 10 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 2
Patients receive clofarabine 20 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 3
Patients receive clofarabine 25 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 4
Patients receive clofarabine 30 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
|---|---|---|---|---|
|
Maximum Tolerated Dose
|
20 mg/day
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 5 yearsCR = no evidence of leukemia with complete blood count recovery (ANC \>1,000 and PLTS \>100k) CRi = no evidence of leukemia but with incomplete blood count recovery
Outcome measures
| Measure |
Dose Level 1
n=4 Participants
Patients receive clofarabine 10 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 2
n=26 Participants
Patients receive clofarabine 20 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 3
n=2 Participants
Patients receive clofarabine 25 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 4
n=3 Participants
Patients receive clofarabine 30 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
|---|---|---|---|---|
|
Treatment Response
CR
|
1 Participants
|
10 Participants
|
1 Participants
|
0 Participants
|
|
Treatment Response
CRi
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Treatment Response
No CR
|
3 Participants
|
15 Participants
|
1 Participants
|
3 Participants
|
SECONDARY outcome
Timeframe: Up to 5 yearsMedian disease-free survival
Outcome measures
| Measure |
Dose Level 1
n=35 Participants
Patients receive clofarabine 10 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 2
Patients receive clofarabine 20 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 3
Patients receive clofarabine 25 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 4
Patients receive clofarabine 30 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
|---|---|---|---|---|
|
Disease Free Survival
|
7.4 median months
Interval 0.0 to 11.0
|
—
|
—
|
—
|
SECONDARY outcome
Timeframe: Up to 5 yearsMedian overall survival
Outcome measures
| Measure |
Dose Level 1
n=35 Participants
Patients receive clofarabine 10 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 2
Patients receive clofarabine 20 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 3
Patients receive clofarabine 25 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
Dose Level 4
Patients receive clofarabine 30 mg PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO
cytarabine: Given SC
|
|---|---|---|---|---|
|
Overall Survival
|
6.8 median months
Interval 1.0 to 47.0
|
—
|
—
|
—
|
Adverse Events
Treatment (Chemotherapy)
Serious events: 24 serious events
Other events: 0 other events
Deaths: 5 deaths
Serious adverse events
| Measure |
Treatment (Chemotherapy)
n=35 participants at risk
Patients receive clofarabine PO QD on days 1-5 and low-dose cytarabine SC BID on days 1-10 or SC QD on days 1-14. Treatment repeats every 21-28 days for up to 4 courses in the absence of disease progression or unacceptable toxicity.
clofarabine: Given PO cytarabine: Given SC
|
|---|---|
|
Infections and infestations
Infections
|
68.6%
24/35 • Number of events 24 • 30 days
Adverse events were not reported by dose level.
|
|
General disorders
Febrile neutropenia
|
22.9%
8/35 • Number of events 8 • 30 days
Adverse events were not reported by dose level.
|
|
General disorders
Septic Shock
|
14.3%
5/35 • Number of events 5 • 30 days
Adverse events were not reported by dose level.
|
|
Infections and infestations
Bacteraemia
|
28.6%
10/35 • Number of events 10 • 30 days
Adverse events were not reported by dose level.
|
|
Infections and infestations
Bacterial infection other than blood
|
20.0%
7/35 • Number of events 7 • 30 days
Adverse events were not reported by dose level.
|
|
Infections and infestations
Fungal infection
|
5.7%
2/35 • Number of events 2 • 30 days
Adverse events were not reported by dose level.
|
|
Cardiac disorders
Arrhythmia
|
8.6%
3/35 • Number of events 3 • 30 days
Adverse events were not reported by dose level.
|
|
Nervous system disorders
Altered Mental Status
|
2.9%
1/35 • Number of events 1 • 30 days
Adverse events were not reported by dose level.
|
|
Cardiac disorders
Heart Failure
|
2.9%
1/35 • Number of events 1 • 30 days
Adverse events were not reported by dose level.
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
2.9%
1/35 • Number of events 1 • 30 days
Adverse events were not reported by dose level.
|
|
Gastrointestinal disorders
Gastrointestinal Bleed
|
2.9%
1/35 • Number of events 1 • 30 days
Adverse events were not reported by dose level.
|
|
General disorders
Syncope
|
2.9%
1/35 • Number of events 1 • 30 days
Adverse events were not reported by dose level.
|
|
Vascular disorders
Stroke
|
2.9%
1/35 • Number of events 1 • 30 days
Adverse events were not reported by dose level.
|
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place