Trial Outcomes & Findings for Clofarabine Plus Low-Dose Cytarabine for Patients With Higher-Risk Myelodysplastic Syndrome (MDS) (NCT NCT01444742)

Last Updated: 2018-07-03

Results Overview

Complete Response Criteria (CR must last for at least 4 weeks): Marrow: \</= 5% myeloblasts with normal maturation of all cell lines; Persistent dysplasia noted; Blood: Hemoglobin (Hb) \>/= 11 g/dL (untransfused, patient not on EPO); Neutrophils \>/= 1x109/L (not on myeloid growth factor); Platelets \>/= 100 \* 109/L (not on thrombopoietic agent); No blasts. Bone marrow aspirate and/or biopsy at the end of course 1 (day 28 +/- 7 days). The method of Thall, Simon, and Estey used to monitor response.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

81 participants

Primary outcome timeframe

4 weeks after first cycle

Results posted on

2018-07-03

Participant Flow

Recruitment Period: 11/2011 to 10/2015

Of the 81 participants registered, one participant was never treated with the study medication. All Participants were registered at The University of Texas MD Anderson Cancer Center.

Participant milestones

Participant milestones
Measure	Clofarabine + Cytarabine Induction: Clofarabine 10 mg/m2 1-2 hours by vein daily for 5 days (days 1-5) Cytarabine 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: Clofarabine 10 mg/m2 1-2 hours by vein daily for 3 days (days 1-3) Cytarabine 20 mg subcutaneously twice daily for 5 days (days 1-5) Clofarabine: Induction: 10 mg/m2 by vein over 1-2 hours daily for 5 days (days 1-5) Consolidation: 10 mg/m2 by vein over 1-2 hours daily for 3 days (days 1-3) Cytarabine: Induction: 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: 20 mg subcutaneously twice daily for 5 days (days 1-5)
Overall Study STARTED	81
Overall Study COMPLETED	80
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Clofarabine + Cytarabine Induction: Clofarabine 10 mg/m2 1-2 hours by vein daily for 5 days (days 1-5) Cytarabine 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: Clofarabine 10 mg/m2 1-2 hours by vein daily for 3 days (days 1-3) Cytarabine 20 mg subcutaneously twice daily for 5 days (days 1-5) Clofarabine: Induction: 10 mg/m2 by vein over 1-2 hours daily for 5 days (days 1-5) Consolidation: 10 mg/m2 by vein over 1-2 hours daily for 3 days (days 1-3) Cytarabine: Induction: 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: 20 mg subcutaneously twice daily for 5 days (days 1-5)
Overall Study Death	1

Baseline Characteristics

Clofarabine Plus Low-Dose Cytarabine for Patients With Higher-Risk Myelodysplastic Syndrome (MDS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Clofarabine + Cytarabine n=81 Participants Induction: Clofarabine 10 mg/m2 1-2 hours by vein daily for 5 days (days 1-5) Cytarabine 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: Clofarabine 10 mg/m2 1-2 hours by vein daily for 3 days (days 1-3) Cytarabine 20 mg subcutaneously twice daily for 5 days (days 1-5) Clofarabine: Induction: 10 mg/m2 by vein over 1-2 hours daily for 5 days (days 1-5) Consolidation: 10 mg/m2 by vein over 1-2 hours daily for 3 days (days 1-3) Cytarabine: Induction: 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: 20 mg subcutaneously twice daily for 5 days (days 1-5)
Age, Categorical <=18 years	0 Participants n=93 Participants
Age, Categorical Between 18 and 65 years	16 Participants n=93 Participants
Age, Categorical >=65 years	65 Participants n=93 Participants
Age, Continuous	71 years n=93 Participants
Sex: Female, Male Female	25 Participants n=93 Participants
Sex: Female, Male Male	56 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	1 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	4 Participants n=93 Participants
Race (NIH/OMB) White	72 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=93 Participants
Region of Enrollment United States	81 Participants n=93 Participants

PRIMARY outcome

Timeframe: 4 weeks after first cycle

Population: One of the eighty-one participants registered on the study were in evaluable for response.

Outcome measures

Outcome measures
Measure	Clofarabine + Cytarabine n=80 Participants Induction: Clofarabine 10 mg/m2 1-2 hours by vein daily for 5 days (days 1-5) Cytarabine 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: Clofarabine 10 mg/m2 1-2 hours by vein daily for 3 days (days 1-3) Cytarabine 20 mg subcutaneously twice daily for 5 days (days 1-5) Clofarabine: Induction: 10 mg/m2 by vein over 1-2 hours daily for 5 days (days 1-5) Consolidation: 10 mg/m2 by vein over 1-2 hours daily for 3 days (days 1-3) Cytarabine: Induction: 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: 20 mg subcutaneously twice daily for 5 days (days 1-5)
Number of Participants With Complete Response (CR)	19 Participants

SECONDARY outcome

Timeframe: 5 years

Overall survival defined as the time interval from study entry date to the date of death due to any cause, measured in days/months. Bayesian time-to-event model used to monitor overall survival.

Outcome measures

Outcome measures
Measure	Clofarabine + Cytarabine n=80 Participants Induction: Clofarabine 10 mg/m2 1-2 hours by vein daily for 5 days (days 1-5) Cytarabine 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: Clofarabine 10 mg/m2 1-2 hours by vein daily for 3 days (days 1-3) Cytarabine 20 mg subcutaneously twice daily for 5 days (days 1-5) Clofarabine: Induction: 10 mg/m2 by vein over 1-2 hours daily for 5 days (days 1-5) Consolidation: 10 mg/m2 by vein over 1-2 hours daily for 3 days (days 1-3) Cytarabine: Induction: 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: 20 mg subcutaneously twice daily for 5 days (days 1-5)
Overall Survival (OS)	10.3 Months Interval 0.5 to 62.0

Adverse Events

Clofarabine + Cytarabine

Serious events: 57 serious events

Other events: 46 other events

Deaths: 16 deaths

Serious adverse events

Serious adverse events
Measure	Clofarabine + Cytarabine n=81 participants at risk Induction: Clofarabine 10 mg/m2 1-2 hours by vein daily for 5 days (days 1-5) Cytarabine 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: Clofarabine 10 mg/m2 1-2 hours by vein daily for 3 days (days 1-3) Cytarabine 20 mg subcutaneously twice daily for 5 days (days 1-5) Clofarabine: Induction: 10 mg/m2 by vein over 1-2 hours daily for 5 days (days 1-5) Consolidation: 10 mg/m2 by vein over 1-2 hours daily for 3 days (days 1-3) Cytarabine: Induction: 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: 20 mg subcutaneously twice daily for 5 days (days 1-5)
Renal and urinary disorders Acute Kidney Injury	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Blood and lymphatic system disorders Anemia	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Infections and infestations Bacteremia	2.5% 2/81 • Number of events 2 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
General disorders Chills	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Gastrointestinal disorders Constipation	2.5% 2/81 • Number of events 2 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
General disorders Death	3.7% 3/81 • Number of events 3 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Gastrointestinal disorders Diarrhea	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
General disorders Duodenal Ulcer	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Respiratory, thoracic and mediastinal disorders Dyspnea	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Metabolism and nutrition disorders Elevated aspartate aminotransferase (AST)	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Blood and lymphatic system disorders Epistaxis	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
General disorders Failure to Thrive	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
General disorders Fall	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
General disorders Fatigue	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
General disorders Fever of Unknown Origin	2.5% 2/81 • Number of events 3 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Renal and urinary disorders Hepatic Failure	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Metabolism and nutrition disorders Hyperbilirubinemia	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Cardiac disorders Hypotension	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Infections and infestations Infection	8.6% 7/81 • Number of events 9 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
General disorders Infusion Reaction	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Blood and lymphatic system disorders Hemorrhage	4.9% 4/81 • Number of events 7 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Infections and infestations Lung Infection	27.2% 22/81 • Number of events 26 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Nervous system disorders Memory Impairment	1.2% 1/81 • Number of events 2 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Musculoskeletal and connective tissue disorders Muscle Weakness	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Cardiac disorders Myocardial Infarction	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Gastrointestinal disorders Nausea and Vomiting	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
General disorders Neck Mass	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Infections and infestations Neutropenic Fever	30.9% 25/81 • Number of events 33 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
General disorders Pain	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Cardiac disorders Pericardial Tamponade	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Musculoskeletal and connective tissue disorders Pseudogout	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Gastrointestinal disorders Rectal Ulcer	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Respiratory, thoracic and mediastinal disorders Respiratory Distress	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Respiratory, thoracic and mediastinal disorders Respiratory Failure	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Infections and infestations Sepsis	8.6% 7/81 • Number of events 7 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
General disorders Severe Deconditioning	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Musculoskeletal and connective tissue disorders Spinal Fracture	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Nervous system disorders Syncopal Event	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Skin and subcutaneous tissue disorders Worsening Sweet Syndrome	1.2% 1/81 • Number of events 1 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.

Other adverse events

Other adverse events
Measure	Clofarabine + Cytarabine n=81 participants at risk Induction: Clofarabine 10 mg/m2 1-2 hours by vein daily for 5 days (days 1-5) Cytarabine 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: Clofarabine 10 mg/m2 1-2 hours by vein daily for 3 days (days 1-3) Cytarabine 20 mg subcutaneously twice daily for 5 days (days 1-5) Clofarabine: Induction: 10 mg/m2 by vein over 1-2 hours daily for 5 days (days 1-5) Consolidation: 10 mg/m2 by vein over 1-2 hours daily for 3 days (days 1-3) Cytarabine: Induction: 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: 20 mg subcutaneously twice daily for 5 days (days 1-5)
Gastrointestinal disorders Constipation	16.0% 13/81 • Number of events 13 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Metabolism and nutrition disorders Elevated Alanine Aminotransferase	21.0% 17/81 • Number of events 17 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
General disorders Fatigue	7.4% 6/81 • Number of events 6 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
General disorders Headache	14.8% 12/81 • Number of events 12 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Metabolism and nutrition disorders Hyperbilirubinemia	22.2% 18/81 • Number of events 18 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Gastrointestinal disorders Nausea	18.5% 15/81 • Number of events 15 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Infections and infestations Neutropenic Fever	8.6% 7/81 • Number of events 9 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.
Skin and subcutaneous tissue disorders Rash	23.5% 19/81 • Number of events 19 • Adverse events captured from the time of participant consent until 30 days after the last dose of drug. AE's can be collected for up to 15 cycles.

Additional Information

Guillermo Garcia-Manero, MD/Professor

The University of Texas MD Anderson Cancer Center

Phone: 713-745-3428

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place