Trial Outcomes & Findings for Decitabine and Clofarabine in Higher Risk Myelodysplastic Syndromes (MDS) (NCT NCT00903760)

Last Updated: 2018-11-15

Results Overview

Percentage of participants with event free survival at 1 year. Event free survival (EFS) where event is defined as either death or transformation to acute myeloid leukemia (AML) (marrow and/or blood blasts \>/= 20%)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

42 participants

Primary outcome timeframe

Assessed at 12 months/1 year

Results posted on

2018-11-15

Participant Flow

Recruitment period: January 28, 2010 to May 7, 2014. All recruitment done at The University of Texas (UT) MD Anderson Cancer Center.

Of the 42 participant enrolled, five were not randomized or treated and are therefore excluded from the trial details. One participant included in group assignment was randomized but not treated as a result of early death.

Participant milestones

Participant milestones
Measure	Decitabine + Clofarabine Drug delivery intravenously (IV) in alternating series of cycles (Decitabine 20 mg/m\^2 for 5 days first 3 cycles, then Clofarabine 10 mg/m\^2 five days for next 3 cycles), pattern repeats for up to 24 cycles.	Decitabine Decitabine 20 mg/m\^2 IV daily for 5 days for a total of 24 courses.
Overall Study STARTED	19	18
Overall Study COMPLETED	0	2
Overall Study NOT COMPLETED	19	16

Reasons for withdrawal

Reasons for withdrawal
Measure	Decitabine + Clofarabine Drug delivery intravenously (IV) in alternating series of cycles (Decitabine 20 mg/m\^2 for 5 days first 3 cycles, then Clofarabine 10 mg/m\^2 five days for next 3 cycles), pattern repeats for up to 24 cycles.	Decitabine Decitabine 20 mg/m\^2 IV daily for 5 days for a total of 24 courses.
Overall Study Disease Progression/Death	8	6
Overall Study Stem Cell Transplant	8	4
Overall Study Physician Decision	1	2
Overall Study Death	0	1
Overall Study Lost to Follow-up	1	0
Overall Study Withdrawal by Subject	1	2
Overall Study Off treatment for long period	0	1

Baseline Characteristics

Decitabine and Clofarabine in Higher Risk Myelodysplastic Syndromes (MDS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Decitabine + Clofarabine n=19 Participants Drug delivery intravenously (IV) in alternating series of cycles (Decitabine 20 mg/m\^2 for 5 days first 3 cycles, then Clofarabine 10 mg/m\^2 five days for next 3 cycles), pattern repeats for up to 24 cycles.	Decitabine n=18 Participants Decitabine 20 mg/m\^2 IV daily for 5 days for a total of 24 courses.	Total n=37 Participants Total of all reporting groups
Age, Customized <=29	2 participants n=5 Participants	0 participants n=7 Participants	2 participants n=5 Participants
Age, Customized 30-39	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Age, Customized 40-49	1 participants n=5 Participants	0 participants n=7 Participants	1 participants n=5 Participants
Age, Customized 50-59	3 participants n=5 Participants	1 participants n=7 Participants	4 participants n=5 Participants
Age, Customized 60-69	4 participants n=5 Participants	7 participants n=7 Participants	11 participants n=5 Participants
Age, Customized 70-79	9 participants n=5 Participants	8 participants n=7 Participants	17 participants n=5 Participants
Age, Customized >=80	0 participants n=5 Participants	1 participants n=7 Participants	1 participants n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants	10 Participants n=7 Participants	17 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	8 Participants n=7 Participants	20 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	14 Participants n=5 Participants	14 Participants n=7 Participants	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 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	1 Participants n=5 Participants	3 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	16 Participants n=5 Participants	15 Participants n=7 Participants	31 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	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Region of Enrollment United States	19 participants n=5 Participants	18 participants n=7 Participants	37 participants n=5 Participants

PRIMARY outcome

Timeframe: Assessed at 12 months/1 year

Population: One of 18 participants in the Decitabine arm was not treated due to early death thus is excluded from analysis.

Outcome measures

Outcome measures
Measure	Decitabine + Clofarabine n=19 Participants Drug delivery intravenously (IV) in alternating series of cycles (Decitabine 20 mg/m\^2 for 5 days first 3 cycles, then Clofarabine 10 mg/m\^2 five days for next 3 cycles), pattern repeats for up to 24 cycles.	Decitabine n=17 Participants Decitabine 20 mg/m\^2 IV daily for 5 days for a total of 24 courses.
Event Free Survival (EFS) at 1 Year	26 percentage of participants	65 percentage of participants

SECONDARY outcome

Timeframe: Up to 6 months

Population: One of 18 participants in the Decitabine arm was not treated due to early death thus is excluded from analysis.

Responses: Complete Remission (CR): Normalization peripheral blood \& bone marrow \</= 5% bone marrow blasts, no evidence dysplasia; peripheral blood granulocyte \>/= 1.0 x 10\^9/L, \& platelet\>/= 100 x 10\^9/L. Partial Remission: all CR criteria if abnormal before treatment except marrow blasts decrease =/\> 50% compared to pretreatment or a less-advanced MDS disease classification than prior to treatment. Hematologic Improvement: Response maintained 8+ weeks: Hemoglobin (pretreatment \< 11 g/dL): improves 1.5 g/dL or reduced by 4 units of red blood cell (RBC) transfusions in 8 weeks compared with pretreatment transfusions in 8 weeks; or Platelet (pretreatment \< 100 x 10\^9/L): absolute increase \>/= 30 x 10\^9/L, starting platelet \> 20 x 10\^9/L OR increase \< 20 x 10\^9/L to \> 20 x 10\^9/L and =/\> 100%. Neutrophil (pretreatment \< 1 x 10\^9/L): increase 100% \& absolute increase \> 0.5 x 10\^9/L.

Outcome measures

Outcome measures
Measure	Decitabine + Clofarabine n=19 Participants Drug delivery intravenously (IV) in alternating series of cycles (Decitabine 20 mg/m\^2 for 5 days first 3 cycles, then Clofarabine 10 mg/m\^2 five days for next 3 cycles), pattern repeats for up to 24 cycles.	Decitabine n=17 Participants Decitabine 20 mg/m\^2 IV daily for 5 days for a total of 24 courses.
Participant Response Complete Remission (CR)	8 participants	9 participants
Participant Response Partial Remission (PR)	0 participants	0 participants
Participant Response Hematologic Improvement (HI)	5 participants	4 participants

Adverse Events

Decitabine + Clofarabine

Serious events: 1 serious events

Other events: 19 other events

Deaths: 0 deaths

Decitabine

Serious events: 1 serious events

Other events: 18 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Decitabine + Clofarabine n=19 participants at risk Drug delivery intravenously (IV) in alternating series of cycles (Decitabine 20 mg/m\^2 for 5 days first 3 cycles, then Clofarabine 10 mg/m\^2 five days for next 3 cycles), pattern repeats for up to 24 cycles.	Decitabine n=18 participants at risk Decitabine 20 mg/m\^2 IV daily for 5 days for a total of 24 courses.
Infections and infestations Lung Infection	0.00% 0/19 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	5.6% 1/18 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Infections and infestations Bacteremia - Escherichia coli (E. coli)	0.00% 0/19 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	5.6% 1/18 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Infections and infestations Sepsis	5.3% 1/19 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	0.00% 0/18 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
General disorders Death	0.00% 0/19 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	5.6% 1/18 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.

Other adverse events

Additional Information

Guillermo Garcia-Manero, MD / Professor, Leukemia

The University of Texas (UT) 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

Measure	Decitabine + Clofarabine n=19 participants at risk Drug delivery intravenously (IV) in alternating series of cycles (Decitabine 20 mg/m\^2 for 5 days first 3 cycles, then Clofarabine 10 mg/m\^2 five days for next 3 cycles), pattern repeats for up to 24 cycles.	Decitabine n=18 participants at risk Decitabine 20 mg/m\^2 IV daily for 5 days for a total of 24 courses.
Infections and infestations Urinary tract infection (UTI)	21.1% 4/19 • Number of events 4 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	27.8% 5/18 • Number of events 5 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Infections and infestations Bacteremia -E. Coli	5.3% 1/19 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	0.00% 0/18 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Infections and infestations Bacteremia-pseudomonas	5.3% 1/19 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	0.00% 0/18 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Musculoskeletal and connective tissue disorders Bilateral joint pain	5.3% 1/19 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	0.00% 0/18 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Infections and infestations Bilateral lower lobe pneumonia	0.00% 0/19 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	5.6% 1/18 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Infections and infestations Cellulitis	15.8% 3/19 • Number of events 3 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	33.3% 6/18 • Number of events 6 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Cardiac disorders Chest Pain	5.3% 1/19 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	0.00% 0/18 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Vascular disorders Deep vein thrombosis -picc line	0.00% 0/19 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	5.6% 1/18 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Blood and lymphatic system disorders Febrile Neutropenia	47.4% 9/19 • Number of events 9 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	50.0% 9/18 • Number of events 9 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Injury, poisoning and procedural complications Fracture-femoral neck	5.3% 1/19 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	0.00% 0/18 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Gastrointestinal disorders Gastrointestinal Bleed	5.3% 1/19 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	5.6% 1/18 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Metabolism and nutrition disorders Hyperglycemia	10.5% 2/19 • Number of events 2 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	5.6% 1/18 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Vascular disorders Hypotension	0.00% 0/19 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	5.6% 1/18 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Infections and infestations Infection - other	10.5% 2/19 • Number of events 2 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	5.6% 1/18 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Nervous system disorders Intracranial hemorrhage	0.00% 0/19 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	5.6% 1/18 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Musculoskeletal and connective tissue disorders Left side weakness	5.3% 1/19 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	0.00% 0/18 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Infections and infestations Respiratory infection	0.00% 0/19 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	11.1% 2/18 • Number of events 2 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Infections and infestations Lung Infection	63.2% 12/19 • Number of events 12 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	11.1% 2/18 • Number of events 2 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Musculoskeletal and connective tissue disorders Muscle weakness in lower limbs	0.00% 0/19 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	5.6% 1/18 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Investigations Neutrophil count decreased	5.3% 1/19 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	5.6% 1/18 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Investigations Platelet count decreased	26.3% 5/19 • Number of events 5 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	0.00% 0/18 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Respiratory, thoracic and mediastinal disorders Pleural effusion	5.3% 1/19 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	0.00% 0/18 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Skin and subcutaneous tissue disorders Rash-extremities	5.3% 1/19 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	0.00% 0/18 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Infections and infestations Sinusitis	10.5% 2/19 • Number of events 2 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	0.00% 0/18 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Skin and subcutaneous tissue disorders Rash	0.00% 0/19 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	5.6% 1/18 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Metabolism and nutrition disorders Tumor Lysis Syndrome	5.3% 1/19 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	0.00% 0/18 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Infections and infestations Vancomycin-resistant enterococci (VRE)	0.00% 0/19 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	5.6% 1/18 • Number of events 1 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.
Respiratory, thoracic and mediastinal disorders sinusitis	0.00% 0/19 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.	11.1% 2/18 • Number of events 2 • Adverse event reporting with each course which is repeated every 4 to 8 weeks, up to 4 years.