Trial Outcomes & Findings for Clofarabine Combinations in Relapsed/Refractory Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS) and Myeloid Blast Phase Chronic Myeloid Leukemia (CML) (NCT NCT00067028)
NCT ID: NCT00067028
Last Updated: 2020-12-08
Results Overview
Response assessed by blood test or bone marrow aspirate following day 21 of induction and then every 2 weeks thereafter until remission or non-response. Complete remission (CR): Disappearance all clinical and/or radiologic evidence of disease; Neutrophil count \> 1.0 x10\^9/L and platelet count \>100x10\^9/L, and normal bone marrow differential (\< 5% blasts). Complete remission without platelet recovery (CRp): Peripheral blood and bone marrow results as for CR, but with platelet counts of \> 20 x 10\^9/L and \< 100 x 10\^9/L. Partial remission (PR): Peripheral blood count recovery as for CR, but with decrease in marrow blasts of \> 50% and not more than 6-25% abnormal cells in the marrow. All other responses considered as failures.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
116 participants
Primary outcome timeframe
Up to 6 years
Results posted on
2020-12-08
Participant Flow
Recruitment Period: December 2003 to October 2009. All participants were recruited at the University of Texas (UT) MD Anderson Cancer Center.
Participant milestones
| Measure |
Clofarabine + Ara-C
Clofarabine 40 mg/m\^2 by vein over 1 hour daily for 5 days.
Ara-C :1 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
|
Clofarabine + Idarubicin
Clofarabine 22.5 mg/m\^2 by vein over 1 hour daily for 5 days.
Idarubicin 10 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
|
Clofarabine + Idarubicin + Ara-C
Clofarabine 22.5 mg/m\^2 by vein over 1 hour daily for 5 days.
Idarubicin 6 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
Ara-C Starting dose: 0.75 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
|
|---|---|---|---|
|
Overall Study
STARTED
|
17
|
36
|
63
|
|
Overall Study
COMPLETED
|
17
|
36
|
63
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Clofarabine Combinations in Relapsed/Refractory Acute Myeloid Leukemia (AML), Myelodysplastic Syndromes (MDS) and Myeloid Blast Phase Chronic Myeloid Leukemia (CML)
Baseline characteristics by cohort
| Measure |
Clofarabine + Ara-C
n=17 Participants
Clofarabine 40 mg/m\^2 by vein over 1 hour daily for 5 days.
Ara-C : 1 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
|
Clofarabine + Idarubicin
n=36 Participants
Clofarabine 22.5 mg/m\^2 by vein over 1 hour daily for 5 days.
Idarubicin 10 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
|
Clofarabine + Idarubicin + Ara-C
n=63 Participants
Clofarabine 22.5 mg/m\^2 by vein over 1 hour daily for 5 days.
Idarubicin 6 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
Ara-C Starting dose: 0.75 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
|
Total
n=116 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=93 Participants
|
0 Participants
n=4 Participants
|
0 Participants
n=27 Participants
|
0 Participants
n=483 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
14 Participants
n=93 Participants
|
28 Participants
n=4 Participants
|
58 Participants
n=27 Participants
|
100 Participants
n=483 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=93 Participants
|
8 Participants
n=4 Participants
|
5 Participants
n=27 Participants
|
16 Participants
n=483 Participants
|
|
Age, Continuous
|
55 years
n=93 Participants
|
57 years
n=4 Participants
|
51 years
n=27 Participants
|
54 years
n=483 Participants
|
|
Sex: Female, Male
Female
|
7 Participants
n=93 Participants
|
26 Participants
n=4 Participants
|
30 Participants
n=27 Participants
|
63 Participants
n=483 Participants
|
|
Sex: Female, Male
Male
|
10 Participants
n=93 Participants
|
10 Participants
n=4 Participants
|
33 Participants
n=27 Participants
|
53 Participants
n=483 Participants
|
|
Region of Enrollment
United States
|
17 participants
n=93 Participants
|
36 participants
n=4 Participants
|
63 participants
n=27 Participants
|
116 participants
n=483 Participants
|
PRIMARY outcome
Timeframe: Up to 6 yearsPopulation: Two participants in the Clofarabine + Idarubicin (CI) arm were not evaluable for response.
Response assessed by blood test or bone marrow aspirate following day 21 of induction and then every 2 weeks thereafter until remission or non-response. Complete remission (CR): Disappearance all clinical and/or radiologic evidence of disease; Neutrophil count \> 1.0 x10\^9/L and platelet count \>100x10\^9/L, and normal bone marrow differential (\< 5% blasts). Complete remission without platelet recovery (CRp): Peripheral blood and bone marrow results as for CR, but with platelet counts of \> 20 x 10\^9/L and \< 100 x 10\^9/L. Partial remission (PR): Peripheral blood count recovery as for CR, but with decrease in marrow blasts of \> 50% and not more than 6-25% abnormal cells in the marrow. All other responses considered as failures.
Outcome measures
| Measure |
Clofarabine + Ara-C
n=17 Participants
Clofarabine 40 mg/m\^2 by vein over 1 hour daily for 5 days.
Ara-C : 1 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
|
Clofarabine + Idarubicin
n=34 Participants
Clofarabine 30 - 40 mg/m\^2 by vein over 1 hour daily for 5 days.
Idarubicin 10 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
|
Clofarabine + Idarubicin + Ara-C
n=63 Participants
Clofarabine 30 - 40 mg/m\^2 by vein over 1 hour daily for 5 days.
Idarubicin 6 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
Ara-C Starting dose: 0.75 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
|
|---|---|---|---|
|
Participants With a Response
CR
|
4 participants
|
9 participants
|
16 participants
|
|
Participants With a Response
CRp
|
2 participants
|
5 participants
|
7 participants
|
|
Participants With a Response
PR
|
0 participants
|
1 participants
|
1 participants
|
SECONDARY outcome
Timeframe: Up to 6 yearsPercentage of participants with complete response following treatment out of all participants in that particular treatment group. Response assessed by blood test or bone marrow aspirate following day 21 of induction and then every 2 weeks thereafter until remission or non-response. Complete remission (CR): Disappearance all clinical and/or radiologic evidence of disease; Neutrophil count \> 1.0 x10\^9/L and platelet count \>100x10\^9/L, and normal bone marrow differential (\< 5% blasts). Complete remission without platelet recovery (CRp): Peripheral blood and bone marrow results as for CR, but with platelet counts of \> 20 x 10\^9/L and \< 100 x 10\^9/L. Partial remission (PR): Peripheral blood count recovery as for CR, but with decrease in marrow blasts of \> 50% and not more than 6-25% abnormal cells in the marrow. All other responses considered as failures.
Outcome measures
| Measure |
Clofarabine + Ara-C
n=17 Participants
Clofarabine 40 mg/m\^2 by vein over 1 hour daily for 5 days.
Ara-C : 1 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
|
Clofarabine + Idarubicin
n=34 Participants
Clofarabine 30 - 40 mg/m\^2 by vein over 1 hour daily for 5 days.
Idarubicin 10 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
|
Clofarabine + Idarubicin + Ara-C
n=63 Participants
Clofarabine 30 - 40 mg/m\^2 by vein over 1 hour daily for 5 days.
Idarubicin 6 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
Ara-C Starting dose: 0.75 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
|
|---|---|---|---|
|
Overall Response Rate (ORR)
|
36 Percentage of Participants
|
44 Percentage of Participants
|
24 Percentage of Participants
|
Adverse Events
Clofarabine + Ara-C
Serious events: 4 serious events
Other events: 17 other events
Deaths: 4 deaths
Clofarabine + Idarubicin
Serious events: 13 serious events
Other events: 36 other events
Deaths: 3 deaths
Clofarabine + Idarubicin + Ara-C
Serious events: 13 serious events
Other events: 63 other events
Deaths: 8 deaths
Serious adverse events
| Measure |
Clofarabine + Ara-C
n=17 participants at risk
Clofarabine 40 mg/m\^2 by vein over 1 hour daily for 5 days.
Ara-C :1 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
|
Clofarabine + Idarubicin
n=36 participants at risk
Clofarabine 22.5 mg/m\^2 by vein over 1 hour daily for 5 days.
Idarubicin 10 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
|
Clofarabine + Idarubicin + Ara-C
n=63 participants at risk
Clofarabine 22.5 mg/m\^2 by vein over 1 hour daily for 5 days.
Idarubicin 6 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
Ara-C Starting dose: 0.75 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
|
|---|---|---|---|
|
Cardiac disorders
Supraventricular Arrhythmia
|
0.00%
0/17 • Up to 6 years
|
0.00%
0/36 • Up to 6 years
|
1.6%
1/63 • Number of events 1 • Up to 6 years
|
|
Blood and lymphatic system disorders
Blood/Bone Marrow
|
0.00%
0/17 • Up to 6 years
|
0.00%
0/36 • Up to 6 years
|
1.6%
1/63 • Number of events 1 • Up to 6 years
|
|
Hepatobiliary disorders
Cholevystitis
|
0.00%
0/17 • Up to 6 years
|
2.8%
1/36 • Number of events 1 • Up to 6 years
|
0.00%
0/63 • Up to 6 years
|
|
General disorders
Death
|
5.9%
1/17 • Number of events 1 • Up to 6 years
|
2.8%
1/36 • Number of events 1 • Up to 6 years
|
3.2%
2/63 • Number of events 2 • Up to 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnea
|
0.00%
0/17 • Up to 6 years
|
2.8%
1/36 • Number of events 1 • Up to 6 years
|
0.00%
0/63 • Up to 6 years
|
|
Blood and lymphatic system disorders
Edema
|
0.00%
0/17 • Up to 6 years
|
2.8%
1/36 • Number of events 1 • Up to 6 years
|
0.00%
0/63 • Up to 6 years
|
|
General disorders
Fatigue
|
0.00%
0/17 • Up to 6 years
|
2.8%
1/36 • Number of events 1 • Up to 6 years
|
0.00%
0/63 • Up to 6 years
|
|
General disorders
Fever
|
0.00%
0/17 • Up to 6 years
|
2.8%
1/36 • Number of events 1 • Up to 6 years
|
0.00%
0/63 • Up to 6 years
|
|
Infections and infestations
Fungal Pneumonia
|
5.9%
1/17 • Number of events 1 • Up to 6 years
|
0.00%
0/36 • Up to 6 years
|
0.00%
0/63 • Up to 6 years
|
|
General disorders
Headache
|
0.00%
0/17 • Up to 6 years
|
2.8%
1/36 • Number of events 1 • Up to 6 years
|
0.00%
0/63 • Up to 6 years
|
|
General disorders
Gastrointestinal Hemorrhage
|
0.00%
0/17 • Up to 6 years
|
2.8%
1/36 • Number of events 1 • Up to 6 years
|
0.00%
0/63 • Up to 6 years
|
|
Metabolism and nutrition disorders
Hyperuricemia
|
0.00%
0/17 • Up to 6 years
|
0.00%
0/36 • Up to 6 years
|
1.6%
1/63 • Number of events 1 • Up to 6 years
|
|
Cardiac disorders
Hypotension
|
0.00%
0/17 • Up to 6 years
|
0.00%
0/36 • Up to 6 years
|
1.6%
1/63 • Number of events 1 • Up to 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.00%
0/17 • Up to 6 years
|
0.00%
0/36 • Up to 6 years
|
1.6%
1/63 • Number of events 2 • Up to 6 years
|
|
Infections and infestations
Infection
|
11.8%
2/17 • Number of events 2 • Up to 6 years
|
8.3%
3/36 • Number of events 3 • Up to 6 years
|
4.8%
3/63 • Number of events 3 • Up to 6 years
|
|
Infections and infestations
Infection (orbit)
|
5.9%
1/17 • Number of events 1 • Up to 6 years
|
0.00%
0/36 • Up to 6 years
|
1.6%
1/63 • Number of events 1 • Up to 6 years
|
|
Infections and infestations
Infection (Skin Abcess)
|
0.00%
0/17 • Up to 6 years
|
2.8%
1/36 • Number of events 1 • Up to 6 years
|
1.6%
1/63 • Number of events 1 • Up to 6 years
|
|
Cardiac disorders
Left Ventricular Systolic Dysfunction
|
0.00%
0/17 • Up to 6 years
|
2.8%
1/36 • Number of events 1 • Up to 6 years
|
0.00%
0/63 • Up to 6 years
|
|
Gastrointestinal disorders
Mucositis
|
0.00%
0/17 • Up to 6 years
|
0.00%
0/36 • Up to 6 years
|
1.6%
1/63 • Number of events 1 • Up to 6 years
|
|
Infections and infestations
Pneumonia
|
0.00%
0/17 • Up to 6 years
|
2.8%
1/36 • Number of events 1 • Up to 6 years
|
0.00%
0/63 • Up to 6 years
|
|
General disorders
Prolonged Myelosuppression
|
0.00%
0/17 • Up to 6 years
|
13.9%
5/36 • Number of events 5 • Up to 6 years
|
1.6%
1/63 • Number of events 1 • Up to 6 years
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Failure
|
0.00%
0/17 • Up to 6 years
|
2.8%
1/36 • Number of events 1 • Up to 6 years
|
1.6%
1/63 • Number of events 1 • Up to 6 years
|
|
Infections and infestations
Sepsis
|
0.00%
0/17 • Up to 6 years
|
0.00%
0/36 • Up to 6 years
|
3.2%
2/63 • Number of events 2 • Up to 6 years
|
|
Gastrointestinal disorders
Small Bowel Obstruction
|
0.00%
0/17 • Up to 6 years
|
2.8%
1/36 • Number of events 1 • Up to 6 years
|
0.00%
0/63 • Up to 6 years
|
|
Nervous system disorders
Syncope
|
0.00%
0/17 • Up to 6 years
|
2.8%
1/36 • Number of events 1 • Up to 6 years
|
1.6%
1/63 • Number of events 1 • Up to 6 years
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
0.00%
0/17 • Up to 6 years
|
0.00%
0/36 • Up to 6 years
|
1.6%
1/63 • Number of events 1 • Up to 6 years
|
|
Reproductive system and breast disorders
Vaginal Hemorrhage
|
0.00%
0/17 • Up to 6 years
|
0.00%
0/36 • Up to 6 years
|
1.6%
1/63 • Number of events 3 • Up to 6 years
|
Other adverse events
| Measure |
Clofarabine + Ara-C
n=17 participants at risk
Clofarabine 40 mg/m\^2 by vein over 1 hour daily for 5 days.
Ara-C :1 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
|
Clofarabine + Idarubicin
n=36 participants at risk
Clofarabine 22.5 mg/m\^2 by vein over 1 hour daily for 5 days.
Idarubicin 10 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
|
Clofarabine + Idarubicin + Ara-C
n=63 participants at risk
Clofarabine 22.5 mg/m\^2 by vein over 1 hour daily for 5 days.
Idarubicin 6 mg/m\^2 by vein over 30 minutes, around one hour after clofarabine, for the first 3 days of 5 day cycle.
Ara-C Starting dose: 0.75 g/m\^2 by vein over 2 hours for 5 days in a row, on Days 1 to 5 of each cycle.
|
|---|---|---|---|
|
Gastrointestinal disorders
Nausea/Vomiting
|
100.0%
17/17 • Number of events 47 • Up to 6 years
|
100.0%
36/36 • Number of events 69 • Up to 6 years
|
100.0%
63/63 • Number of events 78 • Up to 6 years
|
|
Gastrointestinal disorders
Diarrhea
|
100.0%
17/17 • Number of events 47 • Up to 6 years
|
100.0%
36/36 • Number of events 50 • Up to 6 years
|
100.0%
63/63 • Number of events 66 • Up to 6 years
|
|
Gastrointestinal disorders
Constipation
|
100.0%
17/17 • Number of events 17 • Up to 6 years
|
77.8%
28/36 • Number of events 28 • Up to 6 years
|
20.6%
13/63 • Number of events 13 • Up to 6 years
|
|
Gastrointestinal disorders
Mucositis
|
100.0%
17/17 • Number of events 24 • Up to 6 years
|
83.3%
30/36 • Number of events 30 • Up to 6 years
|
42.9%
27/63 • Number of events 27 • Up to 6 years
|
|
Gastrointestinal disorders
Anorexia/Dyspepsia
|
100.0%
17/17 • Number of events 17 • Up to 6 years
|
47.2%
17/36 • Number of events 17 • Up to 6 years
|
30.2%
19/63 • Number of events 19 • Up to 6 years
|
|
Skin and subcutaneous tissue disorders
Rash
|
100.0%
17/17 • Number of events 59 • Up to 6 years
|
100.0%
36/36 • Number of events 63 • Up to 6 years
|
61.9%
39/63 • Number of events 39 • Up to 6 years
|
|
General disorders
CNS
|
100.0%
17/17 • Number of events 24 • Up to 6 years
|
100.0%
36/36 • Number of events 36 • Up to 6 years
|
39.7%
25/63 • Number of events 25 • Up to 6 years
|
|
Cardiac disorders
Cardiac
|
35.3%
6/17 • Number of events 6 • Up to 6 years
|
36.1%
13/36 • Number of events 13 • Up to 6 years
|
15.9%
10/63 • Number of events 10 • Up to 6 years
|
|
Hepatobiliary disorders
Hepatic
|
100.0%
17/17 • Number of events 77 • Up to 6 years
|
100.0%
36/36 • Number of events 52 • Up to 6 years
|
100.0%
63/63 • Number of events 68 • Up to 6 years
|
|
Renal and urinary disorders
Renal
|
70.6%
12/17 • Number of events 12 • Up to 6 years
|
22.2%
8/36 • Number of events 8 • Up to 6 years
|
19.0%
12/63 • Number of events 12 • Up to 6 years
|
Additional Information
Hagop M Kantarjian,MD/Chair, Leukemia
The University of Texas M. D. Anderson Cancer Center
Phone: (713) 792-7026
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place