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Low-dose Oral Clofarabine for the Treatment of IPSS INT-1, INT-2 or HIGH Myelodysplastic Syndromes and Chronic Myelomonocytic Leukemia

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ClinicalTrials.gov Identifier: NCT00708721
Recruitment Status : Terminated (Data analysis revealed sufficient data for safety and efficacy)
First Posted : July 2, 2008
Results First Posted : June 1, 2017
Last Update Posted : June 1, 2017
Sponsor:
Collaborator:
Genzyme, a Sanofi Company
Information provided by (Responsible Party):
University of Utah

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Cancer
Chronic Myelomonocytic Leukemia
Intervention Drug: Clofarabine
Enrollment 11
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Cohort 1: 5 mg/Day for 10 Days Cohort 2: 1 mg/Day for 10 Days Cohort 3: 1 mg/Day for 7 Days Not Evaluable
Hide Arm/Group Description 5 mg/day for 10 out of 28 days 1 mg/day for 10/28 days and for cycle 1 and then 1 mg/day for 7/28 days for cycle 2 onward 1 mg/day for 7/28 days [Not Specified]
Period Title: Overall Study
Started 2 4 3 2
Completed 2 4 3 2
Not Completed 0 0 0 0
Arm/Group Title All Groups
Hide Arm/Group Description [Not Specified]
Overall Number of Baseline Participants 11
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
<=18 years
0
   0.0%
Between 18 and 65 years
4
  36.4%
>=65 years
7
  63.6%
Age, Continuous  
Mean (Full Range)
Unit of measure:  Years
Number Analyzed 11 participants
68.3
(59 to 81)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 11 participants
Female
5
  45.5%
Male
6
  54.5%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 11 participants
11
1.Primary Outcome
Title Number of Participants Who Experienced a Dose-Limiting Toxicity
Hide Description Dose-limiting toxicity was defined as any nonhematologic toxicity grade 3 or greater except for alopecia or nausea (which may be of grade 4 severity), or any grade 4 hematologic toxicity lasting more than 28 days after the last day of therapy.
Time Frame 28 days after the first admistration of oral clofarabine
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
9 out of 11 participants were evaluable for this outcome.
Arm/Group Title Cohort 1: 10 mg/Day for 10 Days Cohort 2: 1 mg/Day for 10 Days Cohort 3: 1 mg/Day for 7 Days Not Evaluable
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 2 4 3 2
Measure Type: Number
Unit of Measure: participants who experienced a DLT
2 4 0 0
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Cohort 1: 10 mg/Day for 10 Days, Cohort 2: 1 mg/Day for 10 Days
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Maximum Tolerated Dose
Estimated Value 1
Estimation Comments Based on cytopenias observed at day 10 (Phase 1 trial only), and the Phase II dose was determined to be 1 mg per day for 7 consecutive days given on a 28 day cycle.
2.Primary Outcome
Title The Overall Response Rate in Response to Low Dose Daily Oral Clofarabine in Patients With High Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia (Dysplastic Type).
Hide Description Response rate was measured as complete, partial and hematologic improvement by modified IWG criteria. For complete remission the following must be present for four weeks in a bone marrow aspirate and biopsy: <5% myeloblasts, normal maturation of all cell lines, persisted dysplasia. Peripheral blood counts need to be hemoglobin >11 g/dL, neutrophils >1000/mm3, platelets>100000/mm3, blasts 0%. Partial remission requires all criteria for complete remission except blasts decreased by >50% over pretreatment. Stable disease is defined as failure to achieve at least partial remission, but no evidence of progression for > 8 weeks. Failure is defined as death during tre3atment or disease progression characterized by worsening of cytopenias, increase in percentage of bone marrow blasts, or progression to a more advanced MDS FAB subtype than pretreatment.
Time Frame 4 weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Two patients were not eligible for analysis.
Arm/Group Title All Evaluable Patients
Hide Arm/Group Description:

All participants enrolled.

Clofarabine: Clofarabine is a rationally designed, second generation purine nucleoside analogue. Clofarabine was designed as a hybrid molecule to overcome the limitations and incorporate the best qualities of both fludarabine (F-ara-A) and cladribine (2-CdA, CdA) both of which are currently approved by various regulatory authorities for treatment of hematologic malignancies.

Overall Number of Participants Analyzed 9
Measure Type: Number
Unit of Measure: participants who experienced a response
3
3.Secondary Outcome
Title Time to Progression to Acute Myeloid Leukemia (AML)
Hide Description Longest documented duration of time until progression to AML.
Time Frame approximately 4 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Cycles are 28 days long. Analysis assessed the longest number of cycles completed on study until progression to AML.
Arm/Group Title All Evaluable Patients
Hide Arm/Group Description:
Only nine of the eleven patients were evaluable for this outcome measure.
Overall Number of Participants Analyzed 9
Measure Type: Number
Unit of Measure: cycles
51
4.Secondary Outcome
Title Response of MDS Patients Treated With Low Dose Daily Oral Clofarabine.
Hide Description Stable disease is defined as failure to achieve at least PR, but no evidence of progression for > 8 weeks.
Time Frame approximately 4 years
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of 11 patients, 9 were evaluable for response. Two patients had stable disease responses.
Arm/Group Title All Evaluable Patients
Hide Arm/Group Description:
All evaluable patients. Eleven patients were enrolled, but only nine were evaluable.
Overall Number of Participants Analyzed 9
Measure Type: Count of Participants
Unit of Measure: Participants
2
  22.2%
5.Secondary Outcome
Title The Effect of Low Dose Daily Oral Clofarabine on Global Methylation in Patients With MDS.
Hide Description Potential genomic changes following low dose daily oral clofarabine administration will be assessed.
Time Frame through end of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data were not collected and the outcome measure was not analyzed
Arm/Group Title All Patients
Hide Arm/Group Description:
All participants enrolled.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
6.Secondary Outcome
Title The Effect of Low Dose Daily Oral Clofarabine on miRNA and mRNA Expression Patterns in Patients With MDS
Hide Description Assessment of potential change in miRNA and mRNA genetic expression patterns in patients following administration of low dose daily clofarabine.
Time Frame through end of treatment
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Data were not collected and the outcome measure was not analyzed
Arm/Group Title All Patients
Hide Arm/Group Description:
All participants enrolled.
Overall Number of Participants Analyzed 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title Number of Participants With Adverse Events
Hide Description NCI CTCAE version 3.0 will be used to assess adverse events. The number of participants experiencing adverse events and the number of adverse events per patient will be documented through the course of study.
Time Frame To 30 days after end of treatment or until full resolution.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
All participants experienced at least 1 adverse event (100% of the patient population; 11/11 participants)
Arm/Group Title All Patients
Hide Arm/Group Description:
All participants enrolled.
Overall Number of Participants Analyzed 11
Measure Type: Number
Unit of Measure: participants experiencing adverse events
11
Time Frame Adverse events were collected after the administration of the study drug and followed until resolution.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title All Groups
Hide Arm/Group Description All patients who received study treatment.
All-Cause Mortality
All Groups
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
All Groups
Affected / at Risk (%)
Total   8/11 (72.73%) 
Blood and lymphatic system disorders   
thrombocytopenia  2/11 (18.18%) 
cytopenia  1/11 (9.09%) 
febrile neutropenia  1/11 (9.09%) 
Cardiac disorders   
congestive heart failure  2/11 (18.18%) 
pulmonary hypertension  1/11 (9.09%) 
decreased ejection fraction  1/11 (9.09%) 
Gastrointestinal disorders   
cholecystitis  1/11 (9.09%) 
Infections and infestations   
cellulitis right forearm  1/11 (9.09%) 
urinary tract infection  1/11 (9.09%) 
e. coli positive  1/11 (9.09%) 
gram positive cocci  1/11 (9.09%) 
Musculoskeletal and connective tissue disorders   
femur fracture  1/11 (9.09%) 
joint swelling  1/11 (9.09%) 
Nervous system disorders   
mental status change  1/11 (9.09%) 
stroke  1/11 (9.09%) 
Renal and urinary disorders   
renal failure  1/11 (9.09%) 
Reproductive system and breast disorders   
Ovarian abscess  1/11 (9.09%) 
Respiratory, thoracic and mediastinal disorders   
pneumonia  2/11 (18.18%) 
hypoxia  1/11 (9.09%) 
pleural effusion  1/11 (9.09%) 
Vascular disorders   
Subdural hematoma  1/11 (9.09%) 
1
Term from vocabulary, NCI CTCAE version 3.
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
All Groups
Affected / at Risk (%)
Total   11/11 (100.00%) 
Blood and lymphatic system disorders   
anemia  7/11 (63.64%) 
leukopenia  4/11 (36.36%) 
lymphopenia  5/11 (45.45%) 
neutropenia  6/11 (54.55%) 
splenomegaly  1/11 (9.09%) 
thrombocytopenia  9/11 (81.82%) 
hematomas  1/11 (9.09%) 
petechia  4/11 (36.36%) 
neutropenic fever  1/11 (9.09%) 
Cardiac disorders   
Afibrilation with RVR  1/11 (9.09%) 
Atrial Flutter with AV Block  1/11 (9.09%) 
Ventricular Tachycardia  1/11 (9.09%) 
Cardiomegaly  2/11 (18.18%) 
Hypertension  1/11 (9.09%) 
Inferior Cardiac Infarct  1/11 (9.09%) 
pericarditis  1/11 (9.09%) 
elevated PTT  1/11 (9.09%) 
pericardial thickening  1/11 (9.09%) 
Eye disorders   
left eye redness  1/11 (9.09%) 
eye scratch  1/11 (9.09%) 
Gastrointestinal disorders   
vomiting  2/11 (18.18%) 
abdominal distention  1/11 (9.09%) 
abdominal pain  5/11 (45.45%) 
blood blisters in mouth  1/11 (9.09%) 
constipation  2/11 (18.18%) 
diarrhea  3/11 (27.27%) 
flatulence  1/11 (9.09%) 
heart burn  1/11 (9.09%) 
mouth sores  1/11 (9.09%) 
nausea  4/11 (36.36%) 
oral thrush  2/11 (18.18%) 
oral pain  1/11 (9.09%) 
throat pain  1/11 (9.09%) 
bleeding in mouth  1/11 (9.09%) 
General disorders   
diaphoretic  1/11 (9.09%) 
fatigue  7/11 (63.64%) 
fever  3/11 (27.27%) 
edema (bilateral lower extremity)  3/11 (27.27%) 
pedal edema  1/11 (9.09%) 
chest pain  3/11 (27.27%) 
pain at port site  1/11 (9.09%) 
Infections and infestations   
c. differential positive  1/11 (9.09%) 
cellulitis  1/11 (9.09%) 
eye infection  1/11 (9.09%) 
head cold  1/11 (9.09%) 
infections with unknown ANC  1/11 (9.09%) 
prostatitis  1/11 (9.09%) 
sepsis  1/11 (9.09%) 
sore throat  1/11 (9.09%) 
upper respiratory infection  2/11 (18.18%) 
yeast infection  1/11 (9.09%) 
urinary tract infection  2/11 (18.18%) 
Injury, poisoning and procedural complications   
brusing  3/11 (27.27%) 
hernia  1/11 (9.09%) 
Investigations   
elevated alkaline phosphatase  3/11 (27.27%) 
elevated ALT  2/11 (18.18%) 
elevated amylase  1/11 (9.09%) 
elevated AST  4/11 (36.36%) 
Hyperbilirubinemia  3/11 (27.27%) 
increased creatinine  3/11 (27.27%) 
Metabolism and nutrition disorders   
anorexia  4/11 (36.36%) 
elevated uric acid  1/11 (9.09%) 
hypercalcemia  1/11 (9.09%) 
hyperglycemia  7/11 (63.64%) 
Hypoalbuminemia  6/11 (54.55%) 
hypocalcemia  2/11 (18.18%) 
hypoglycemia  3/11 (27.27%) 
hyponatremia  2/11 (18.18%) 
hypokelmia  2/11 (18.18%) 
rib pain  1/11 (9.09%) 
Musculoskeletal and connective tissue disorders   
bilateral leg weakness  1/11 (9.09%) 
fracture  2/11 (18.18%) 
hand laceration  1/11 (9.09%) 
muscle cramps  1/11 (9.09%) 
muscle weakness  1/11 (9.09%) 
back pain  4/11 (36.36%) 
joint pain  1/11 (9.09%) 
right knee pain  1/11 (9.09%) 
arthritis  1/11 (9.09%) 
bone pain  1/11 (9.09%) 
Nervous system disorders   
confusion  2/11 (18.18%) 
dizziness  3/11 (27.27%) 
drowsiness  1/11 (9.09%) 
hallucination  1/11 (9.09%) 
neuropathy: cranial  1/11 (9.09%) 
neuropathy: motor  1/11 (9.09%) 
anxiety  2/11 (18.18%) 
syncope  1/11 (9.09%) 
headache  3/11 (27.27%) 
Psychiatric disorders   
insomnia  2/11 (18.18%) 
Renal and urinary disorders   
dysuria  1/11 (9.09%) 
Respiratory, thoracic and mediastinal disorders   
allergic rhinits  1/11 (9.09%) 
atelectasis  2/11 (18.18%) 
bronchitis  1/11 (9.09%) 
chest congestion  1/11 (9.09%) 
cough  5/11 (45.45%) 
crackles in lungs  1/11 (9.09%) 
Dyspenia  3/11 (27.27%) 
pleural effusion  3/11 (27.27%) 
pneumonia  3/11 (27.27%) 
pulmonary edema  1/11 (9.09%) 
wheezing  1/11 (9.09%) 
Skin and subcutaneous tissue disorders   
cracked lips  1/11 (9.09%) 
dry skin  2/11 (18.18%) 
itching  1/11 (9.09%) 
lesions  4/11 (36.36%) 
rash: erythemia  3/11 (27.27%) 
ulceration  2/11 (18.18%) 
night sweats  1/11 (9.09%) 
erythematous  2/11 (18.18%) 
Vascular disorders   
hot flashes  1/11 (9.09%) 
lower extremity phlebitis  1/11 (9.09%) 
superficial thrombosis  1/11 (9.09%) 
1
Term from vocabulary, NCI CTCAE version 3.
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Paul Shami
Organization: Huntsman Cancer Institute
Phone: 801-585-0100
Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT00708721     History of Changes
Other Study ID Numbers: HCI26135
First Submitted: June 27, 2008
First Posted: July 2, 2008
Results First Submitted: July 21, 2016
Results First Posted: June 1, 2017
Last Update Posted: June 1, 2017