Trial Outcomes & Findings for A Dose Confirmation Study of Oral Clofarabine for Adult Patients Previously Treated for Myelodysplastic Syndromes (MDS) (NCT NCT00531232)

Last Updated: 2022-03-24

Results Overview

Overall Response: complete remission(CR) or marrow CR or partial remission (PR), or hematologic improvement (HI) in participants with myelodysplastic syndromes (MDS);CR or CR with incomplete count recovery(CRi),or PR in participants with secondary acute myeloid leukemia (sAML). Per International Working Group (IWG) criteria, CR:\<= 5% myeloblasts in bone marrow; persistent dysplasia had to be noted; peripheral blood showing hemoglobin (Hgb)\>=11g/dL, platelets \>=100\*10\^9/L,neutrophils \>=1\*10\^9/L, blasts 0%. Marrow CR:\<=5%myeloblasts in bone marrow and decreased by \>=50% over pretreatment; any HI response in peripheral blood. CRi: meeting all criteria for CR except for residual thrombocytopenia (platelet \<100\*10\^9/L) or neutropenia (ANC \<1.0\*10\^9/L). PR: all CR criteria if abnormal before treatment except that marrow blasts should have decreased by \>=50% over pretreatment but still \>5%. HI: meeting any of the erythroid, platelet, or neutrophil improvement categories for at least 8 weeks.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

38 participants

Primary outcome timeframe

From date of randomization until disease recurrence or death, whichever occurred first (maximum study duration: up to 4 years)

Results posted on

2022-03-24

Participant Flow

The study was conducted at 6 active centers in United States. A total of 38 participants were enrolled between 07 May 2007 and 07 February 2011.

Participants initially received either 55 or 35 milligrams per day (mg/day) of Clofarabine orally. After a review of the safety data, the dose was lowered to 25 mg/day; and further participants were enrolled at the 25 mg/day dose level.

Participant milestones

Participant milestones
Measure	Clofarabine 55 mg/Day Participants received Clofarabine 55 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 35 mg/Day Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
Overall Study STARTED	4	9	25
Overall Study Treated	4	8	24
Overall Study COMPLETED	0	0	0
Overall Study NOT COMPLETED	4	9	25

Reasons for withdrawal

Reasons for withdrawal
Measure	Clofarabine 55 mg/Day Participants received Clofarabine 55 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 35 mg/Day Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
Overall Study Investigator decision	0	0	4
Overall Study Participants refused further treatment	0	1	2
Overall Study Adverse events (AEs)	1	2	2
Overall Study Treatment failure	1	3	7
Overall Study Disease recurrence	0	0	1
Overall Study Deceased	2	2	2
Overall Study Withdrawal by Subject	0	1	2
Overall Study Other	0	0	5

Baseline Characteristics

A Dose Confirmation Study of Oral Clofarabine for Adult Patients Previously Treated for Myelodysplastic Syndromes (MDS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Clofarabine 55 mg/Day n=4 Participants Participants received Clofarabine 55 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 35 mg/Day n=8 Participants Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=24 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Total n=36 Participants Total of all reporting groups
Age, Continuous	72.0 years STANDARD_DEVIATION 4.08 • n=5 Participants	68.8 years STANDARD_DEVIATION 9.30 • n=7 Participants	69.9 years STANDARD_DEVIATION 8.68 • n=5 Participants	69.9 years STANDARD_DEVIATION 8.31 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	2 Participants n=7 Participants	13 Participants n=5 Participants	16 Participants n=4 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants	20 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 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	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	3 Participants n=4 Participants
Race (NIH/OMB) White	4 Participants n=5 Participants	8 Participants n=7 Participants	21 Participants n=5 Participants	33 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: From date of randomization until disease recurrence or death, whichever occurred first (maximum study duration: up to 4 years)

Population: Analysis was performed on modified Full Analysis Set (mFAS) that included participants assigned to all doses who had received at least 1 dose of clofarabine, excluding participants treated at 55 mg. Data for this outcome measure (OM) was not planned to be collected and analyzed for Clofarabine 55 mg/day arm.

Outcome measures

Outcome measures
Measure	Clofarabine 35 mg/Day n=8 Participants Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=24 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
Percentage of Participants With Overall Response	13 percentage of participants Interval 0.0 to 26.75	25 percentage of participants Interval 10.58 to 37.77	—

SECONDARY outcome

Timeframe: From first documentation of response to date of documentation of disease relapse, progression or death due to any cause, whichever occurs first (maximum study duration: up to 4 years)

Population: Analysis was performed on subset of participants who had response. Data for this OM was not planned to be collected and analyzed for Clofarabine 55 mg/day arm.

DoR: time (in months) from 1st documentation of response to date of 1st documentation of disease relapse, progression or death due to any cause, whichever occured first. Response defined as CR, marrow CR, or PR (MDS participants) and CR/CRi (sAML participants). Per IWG criteria, relapse defined as: return to pretreatment bone marrow blast %; decrease of \>=50% from maximum remission levels; reduction in Hgb by \>=1.5g/dL.CR:\<= 5%myeloblasts in bone marrow; persistent dysplasia; peripheral blood showing Hgb\>=11g/dL. Marrow CR:\<=5%myeloblasts (bone marrow) and decreased by \>=50% over pretreatment; any HI response in peripheral blood. CRi:meeting all criteria for CR except for residual thrombocytopenia/neutropenia. PR: all CR criteria if abnormal before treatment except that marrow blasts should have decreased by \>=50%. Progression: at least 50% decrease from maximum remission/response in granulocytes/platelets; reduction in Hgb by \>=2g/dL; transfusion dependence. Analyzed by Kaplan-Meier.

Outcome measures

Outcome measures
Measure	Clofarabine 35 mg/Day n=1 Participants Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=6 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
Duration of Response (DoR)	12.5 months	3.2 months Interval 1.6 to 6.2	—

SECONDARY outcome

Timeframe: From date of randomization until disease recurrence or death, whichever occurred first (maximum study duration: up to 4 years)

Population: Analysis was performed on mFAS. Data for this OM was not planned to be collected and analyzed for Clofarabine 55 mg/day arm.

Per IWG criteria, HI was defined as meeting any of the erythroid, platelet,and/or neutrophil independence categories for at least 8 consecutive weeks. Erythroid response (pre-treatment,\<11 grams per deciliter \[g/dL\]) was defined as Hgb increased by \>=1.5 g/dL;relevant reduction of units of red blood cell (RBC) transfusion by an absolute number of at least 4 RBC transfusion/8 weeks compared with the pretreatment transfusion number in the previous 8 weeks; only RBC transfusions given for Hgb of \<=9.0 g/dL pre-treatment counted in the RBC transfusion response evaluation. Platelet response(pretreatment, \<100\*109/L) was defined as absolute increase of \>=30\*109/L for participants starting with \>20\*109/L platelets, increase from \<20\*109/L to \>20\*109/L and by at least 100%. Neutrophil response (pre-treatment, \<1.0\*109/L) was defined by at least 100% increase and an absolute increase \>0.5\*109/L. Number of participants who achieved HI for MDS participants only was reported in outcome measure.

Outcome measures

Outcome measures
Measure	Clofarabine 35 mg/Day n=8 Participants Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=24 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
Number of Participants Who Achieved Hematologic Improvement (HI)	0 Participants	3 Participants	—

SECONDARY outcome

Timeframe: From date of randomization until disease recurrence or death, whichever occurred first (maximum study duration: up to 4 years)

Population: Analysis was performed on mFAS. Data for this OM was not planned to be collected and analyzed for Clofarabine 55 mg/day arm.

OR was defined as a best response of CR, marrow CR, or PR in participants with MDS or a best response of CR or CRi in participants with sAML. As per IWG criteria, CR was defined as the following: bone marrow \<=5% myeloblasts with normal maturation of all cell lines; persistent dysplasia had to be noted; peripheral blood showing hemoglobin \>=11 g/dL, platelets \>=100\*10\^9/L, neutrophils \>=1\*10\^9/L, blasts 0%. Marrow CR was defined as: bone marrow \<=5% myeloblasts and decreased by \>=50% over pretreatment; any HI response in peripheral blood had to be noted. CRi was defined as meeting all criteria for CR except for residual thrombocytopenia (platelet count \<100\*10\^9/L) or neutropenia (ANC \<1.0\*10\^9/L). PR was defined as all CR criteria if abnormal before treatment except that marrow blasts should have decreased by \>=50% over pre-treatment but still \>5%. HI was defined as meeting any of the erythroid, platelet, or neutrophil improvement categories for at least 8 weeks.

Outcome measures

Outcome measures
Measure	Clofarabine 35 mg/Day n=8 Participants Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=24 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
Percentage of Participants Achieving Overall Remission (OR)	13 percentage of participants Interval 0.0 to 26.75	25 percentage of participants Interval 10.58 to 37.77	—

SECONDARY outcome

Timeframe: From date of randomization until disease recurrence or death, whichever occurred first (maximum study duration: up to 4 years)

Population: Analysis was performed on mFAS. Data for this OM was not planned to be collected and analyzed for Clofarabine 55 mg/day arm.

Time to AML transformation was defined as time (in months) from date of the first dose of oral Clofarabine to the date of AML transformation, (i.e., the earliest date when participants experienced bone marrow or peripheral blasts \>30%). The analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Clofarabine 35 mg/Day n=8 Participants Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=24 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
Time to Acute Myeloid Leukemia (AML) Transformation	4.2 months Interval 3.1 to Upper limit of Confidence Interval (CI) was not estimable because the curve's upper CI bound had not crossed 50% survival threshold.	NA months Interval 5.2 to Median was not estimable because the curve's had not crossed 50% survival threshold and upper limit of CI was not estimable because the curve's upper CI bound had not crossed 50% survival threshold.	—

SECONDARY outcome

Timeframe: From date of first dose of study drug until date of death due to any cause (maximum study duration: up to 4 years)

Population: Analysis was performed on mFAS. Data for this OM was not planned to be collected and analyzed for Clofarabine 55 mg/day arm.

OS defined as date of the first dose of oral Clofarabine until date of death due to any cause. If death was not observed, the participant was censored at the earliest of the last date the participant was known to be alive or the study cut-off date. The analysis was performed by Kaplan-Meier method.

Outcome measures

Outcome measures
Measure	Clofarabine 35 mg/Day n=8 Participants Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=24 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
Overall Survival (OS)	4.8 months Interval 0.6 to 7.4	7.3 months Interval 2.8 to Upper limit of CI was not estimable because the curve's upper CI bound had not crossed 50% survival threshold.	—

SECONDARY outcome

Timeframe: Cycle 1 (28 days)

Population: Analysis was performed on all participants who received study drug.

The MTD was the highest dose level of Clofarabine that caused less than (\<) 2 participants to experience unacceptable drug-related toxicities after receiving 1 or more of the initial 5 daily doses of Clofarabine. Unacceptable drug-related toxicities included: drug-related prolonged myelosuppression, which was defined as hypocellular bone marrow with \<5 percent (%) cellularity at 6 weeks after starting treatment, which required a 1-dose level reduction for subsequent cycles; Common Terminology Criteria for Adverse Events (CTCAE) Grade 4 drug-related non-hematologic toxicity; CTCAE Grade 3 drug-related non-hematologic toxicity that either recovered to Baseline grade but was recurrent to Grade 3 upon re-treatment during the first cycle or did not recover to Grade 1 or Baseline within 3 weeks when the drug was held or dose reduced; drug-related non-hematologic toxicity that resulted in non-completion of at least 4 daily doses of oral Clofarabine at the original assigned dose level.

Outcome measures

Outcome measures
Measure	Clofarabine 35 mg/Day n=4 Participants Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=8 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=24 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
Maximum Tolerated Dose (MTD) of Oral Clofarabine	25 mg/day	25 mg/day	25 mg/day

SECONDARY outcome

Timeframe: From Baseline up to 45 days post last dose of study drug (maximum study duration: up to 4 years)

Population: Analysis was performed on FAS.

Febrile neutropenia was defined as fever (e.g., greater than or equal to (\>=) 38.5 Celsius (°C) on a single occasion, or greater than (\>) 38°C on 2 occasions within 12 hours) in the setting of neutropenia (defined as Absolute Neutrophil Count \<1.0\*10\^9/liter \[L\]).

Outcome measures

Outcome measures
Measure	Clofarabine 35 mg/Day n=4 Participants Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=8 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=24 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
Number of Participants With Febrile Neutropenia	1 Participants	1 Participants	13 Participants

SECONDARY outcome

Timeframe: From Baseline up to 45 days post last dose of study drug (maximum duration: up to 4 years)

Population: Analysis was performed on FAS.

Adverse Event (AE): any undesirable physical, psychological/behavioral effect experienced by participant during their participation in clinical study, with study drug usage, whether or not product related.Treatment Emergent AEs (TEAEs): AEs that developed, worsened, or became serious during treatment period (from signature of informed consent form up to 45 days post last dose). Serious AE (SAE):any untoward medical occurrence that at any dose resulted in death, was life-threatening, required inpatient hospitalization/prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/birth defect, medically important event. Per National Cancer Institute (NCI)-CTCAE v3.0 severity for each AE were graded as: Grade 1=Mild AE; Grade 2=Moderate AE; Grade 3=Severe AE, Grade 4=Life-threatening/disabling AE and Grade 5=Death related to AE. Participants with TEAEs, SAEs, death, discontinuations, Grade 4 and 5 toxicities were reported.

Outcome measures

Outcome measures
Measure	Clofarabine 35 mg/Day n=4 Participants Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=8 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=24 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
Number of Participants With Adverse Events (AEs) Any TEAE	4 Participants	8 Participants	24 Participants
Number of Participants With Adverse Events (AEs) Any treatment emergent SAE	4 Participants	6 Participants	19 Participants
Number of Participants With Adverse Events (AEs) Any TEAE leading to discontinuation	1 Participants	2 Participants	2 Participants
Number of Participants With Adverse Events (AEs) Any TEAE leading to death	4 Participants	7 Participants	14 Participants
Number of Participants With Adverse Events (AEs) Deaths within 45 days of last dose	3 Participants	3 Participants	3 Participants
Number of Participants With Adverse Events (AEs) Grade 4 Toxicities	1 Participants	4 Participants	18 Participants
Number of Participants With Adverse Events (AEs) Grade 5 Toxicities	3 Participants	4 Participants	4 Participants

SECONDARY outcome

Timeframe: Within 30 days of first dose administered on Day 1 of Cycle 1

Population: Analysis was performed on FAS.

Outcome measures

Outcome measures
Measure	Clofarabine 35 mg/Day n=4 Participants Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=8 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=24 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
Number of Participants Who Reported Death Within 30 Days of First Dose	2 Participants	1 Participants	1 Participants

SECONDARY outcome

Timeframe: Cycle 1 (28 days)

Population: Analysis was performed on FAS.

Unacceptable drug-related toxicities included: drug-related prolonged myelosuppression, which was defined as hypocellular bone marrow with \<5% cellularity at 6 weeks after starting treatment, which required a 1-dose level reduction for subsequent cycles; CTCAE Grade 4 drug-related non-hematologic toxicity; CTCAE Grade 3 drug-related non-hematologic toxicity that either recovered to Baseline grade but was recurrent to Grade 3 upon re-treatment during the first cycle or did not recover to Grade 1 or Baseline within 3 weeks when the drug was held or dose reduced; drug-related non-hematologic toxicity that resulted in non-completion of at least 4 daily doses of oral clofarabine at the original assigned dose level. Participants with unacceptable drug-related toxicities during Cycle 1 only was reported in the outcome measure.

Outcome measures

Outcome measures
Measure	Clofarabine 35 mg/Day n=4 Participants Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=8 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=24 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
Number of Participants With Unacceptable Drug-related Toxicities During Cycle 1 Any unacceptable drug-related toxicities	0 Participants	1 Participants	0 Participants
Number of Participants With Unacceptable Drug-related Toxicities During Cycle 1 Drug-related prolonged myelosuppression	0 Participants	0 Participants	0 Participants
Number of Participants With Unacceptable Drug-related Toxicities During Cycle 1 Grade 4 drug-related non-haematologic toxicity	0 Participants	1 Participants	0 Participants
Number of Participants With Unacceptable Drug-related Toxicities During Cycle 1 Grade 3 drug-related recurrent or persistent non-haematologic toxicity	0 Participants	0 Participants	0 Participants
Number of Participants With Unacceptable Drug-related Toxicities During Cycle 1 Drug-related toxicity precluding completion of at least 4 daily doses	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Pre-dose and at 1, 3, and 5 hours Post-dose on Day 1 of Cycle 1

Population: Analysis was performed on PK population that included all participants who had received at least 1 dose of oral Clofarabine and had at least 1 sample available for PK analysis.

Cmax was defined as maximum observed plasma concentration of study drug.

Outcome measures

Outcome measures
Measure	Clofarabine 35 mg/Day n=4 Participants Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=8 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=23 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
Pharmacokinetics (PK) Parameter: Maximum Observed Plasma Concentration (Cmax) of Clofarabine	158.25 nanograms per milliliter Standard Deviation 55.446	79.613 nanograms per milliliter Standard Deviation 39.597	47.813 nanograms per milliliter Standard Deviation 44.745

SECONDARY outcome

Timeframe: Pre-dose and at 1, 3, and 5 hours Post-dose on Day 1 of Cycle 1

Population: Analysis was performed on PK population.

Tmax was defined as the time to reach Cmax (maximum observed plasma concentration).

Outcome measures

Outcome measures
Measure	Clofarabine 35 mg/Day n=4 Participants Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=8 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=23 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
PK Parameter: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Clofarabine	2.02 hours Interval 1.0 to 3.03	1 hours Interval 1.0 to 3.0	2 hours Interval 0.92 to 4.0

SECONDARY outcome

Timeframe: Pre-dose and at 1, 3, and 5 hours Post-dose on Day 1 of Cycle 1

Population: Analysis was performed on PK population.

AUC0-last was defined as area under the concentration-time curve from time 0 to time of last measurable plasma concentration.

Outcome measures

Outcome measures
Measure	Clofarabine 35 mg/Day n=4 Participants Participants received Clofarabine 35 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=8 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).	Clofarabine 25 mg/Day n=23 Participants Participants received Clofarabine 25 mg/day orally for 5 consecutive days of each 28-day treatment cycle until disease progression or death, whichever comes first (maximum study duration: up to 4 years).
PK Parameter: Area Under the Concentration-time Curve From Time 0 to Time of Last Measurable Plasma Concentration (AUC0-last) of Clofarabine	590.188 nanograms*hours per milliliter Standard Deviation 192.187	194.084 nanograms*hours per milliliter Standard Deviation 150.035	144.604 nanograms*hours per milliliter Standard Deviation 124.598

Adverse Events

Clofarabine 25 mg/Day

Serious events: 19 serious events

Other events: 24 other events

Deaths: 14 deaths

Clofarabine 35 mg/Day

Serious events: 6 serious events

Other events: 8 other events

Deaths: 7 deaths

Clofarabine 55 mg/Day

Serious events: 4 serious events

Other events: 4 other events

Deaths: 4 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Genzyme, a Sanofi Company

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.
Publication restrictions are in place

Restriction type: OTHER