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Clofarabine Plus Low-Dose Cytarabine for the Treatment of Patients With Higher-Risk Myelodysplastic Syndrome (MDS) Who Have Been Relapsing After, or Are Refractory to, Hypomethylator Therapy

Phase 2
18 Years
Open (Enrolling)
Leukemia, Myeloproliferative Diseases

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Trial Information

Clofarabine Plus Low-Dose Cytarabine for the Treatment of Patients With Higher-Risk Myelodysplastic Syndrome (MDS) Who Have Been Relapsing After, or Are Refractory to, Hypomethylator Therapy

Induction Cycles:

If you are found to be eligible to take part in the study, on Days 1-5 of each cycle , you
will receive clofarabine by vein over 1-2 hours.

On Days 1-7 of each cycle, you will receive cytarabine by injection under the skin over
several seconds 2 times a day.

You may receive up to 3 cycles at this dose and schedule (also called "induction cycles").
There are 7 treatment days in each cycle but the total length of one cycle (including rest
and recovery period) is usually between 4 and 8 weeks.

Consolidation Cycles:

After you have completed the Induction Cycles, if you show a response to treatment, you can
then continue with up to a total of 12 more cycles of therapy, which will be called
"consolidation cycles". Not every participant may be able to receive all 12 consolidation
cycles. The actual number that you will receive depends on whether or not you maintain the
response and how you are able to tolerate ongoing therapy. There will be 4-8 weeks between
each consolidation cycle depending on any side effects you may be having and your blood

During consolidation cycles you will receive clofarabine on Days 1-3 by vein over 1-2
hours. You will receive cytarabine by injection under the skin over several seconds 2 times
a day .

Induction and Consolidation Cycles:

On the days when you receive clofarabine and cytarabine (Days 1-5 during induction and Days
1-3 during consolidation), the clofarabine will be given about 3-6 hours before the
cytarabine injections. You can be taught to give cytarabine injections to yourself. In this
case, you can leave the clinic after receiving clofarabine. You will be required to record
the injections of cytarabine in a diary unless you receive the treatments while you are in
the hospital.

Study Visits:

On Day 1 of every cycle (+/- 7 days):

- You will have a physical exam, including measurements of your weight and vital signs.

- Your performance status will be recorded.

- Blood (about 1-2 teaspoons) will be drawn for routine tests.

About 4 weeks after you started your first cycle, you may have a bone marrow aspirate to
check the status of the disease. After that, you may have repeat bone marrow aspirates when
the doctor thinks it is needed.

It is recommended that you stay in Houston for up to the first 4 weeks of treatment. After
that, you will need to return to Houston before each induction cycle. If you continue with
the consolidation you can receive these treatments by your local oncologist. However, you
have to return to Houston at least every 3 months for your study visits.

Length of Study:

You may continue taking the study drugs for up to 15 cycles. You will no longer be able to
take the study drugs if the disease gets worse, if intolerable side effects occur, or if you
are unable to follow study directions.

This is an investigational study. Clofarabine is FDA approved and commercially available
for use in pediatric patients with acute lymphoblastic leukemia. Its use in adults and in
patients with MDS is investigational.

Cytarabine is FDA approved and commercially available for use in patients with AML.

Up to 80 patients will take part in this study. All be enrolled at MD Anderson.

Inclusion Criteria:

1. Age >/= 18 years.

2. Diagnosis of MDS confirmed within 10 weeks prior to study entry according to WHO or
FAB criteria. Patients are either not eligible for or choose not to proceed with a
stem cell transplant.

3. MDS classified as follows: RAEB-1 (5%-9% BM blasts); RAEB-2 (10%-19% BM Blasts); CMML
(5%-19% BM blasts); RAEB-t (20%-29% BM blasts) AND/OR by IPSS: intermediate-2 and
high risk patients.

4. No response, progression, or relapse (according to 2006 IWG criteria) following at
least 4 cycles of either azacitidine or decitabine, which were completed within the
last 2 years - AND/OR - intolerance to azacitidine or decitabine defined as
drug-related >/= grade 3 hepatic or renal toxicity leading to treatment
discontinuation during the preceding 2 years.

5. Eastern Cooperative Oncology Group (ECOG) performance status of
6. Willing to adhere to and comply with all prohibitions and restrictions specified in
the protocol.

7. Patient (or patient's legally authorized representative) must have signed an informed
consent document indicating that the patient understands the purpose of and
procedures required for the study and is willing to participate in the study.

Exclusion Criteria:

1. Uncontrolled intercurrent illness including, but not limited to, symptomatic
congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.

2. Active infection not adequately responding to appropriate antibiotics (i.e. ongoing
temperatures of >/= 38 degree Celsius).

3. Total bilirubin >/= 1.5 mg/dL and not related to hemolysis or Gilbert's disease.
Patients with total bilirubin >/= 1.5 mg/dL to 3 mg/dL are eligible if at least 75%
of the bilirubin is indirect.

4. Alanine transaminase (ALT/SGPT) or aspartate transaminase (AST/SGOT) >/= 2.5 x the
upper limit of normal.

5. Serum creatinine > 1.5 mg/dL.

6. Female patients who are pregnant or lactating.

7. Patients with reproductive potential who are unwilling to following contraception
requirements (including condom use for males with sexual partners, and for females:
prescription oral contraceptives [birth control pills], contraceptive injections,
intrauterine devices [IUD], double-barrier method [spermicidal jelly or foam with
condoms or diaphragm], contraceptive patch, or surgical sterilization) throughout the

8. Female patients with reproductive potential who do not have a negative urine or blood
beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.

9. Patients receiving any other concurrent investigational agent or chemotherapy,
radiotherapy, or immunotherapy.

10. No prior treatment with cytarabine or clofarabine. Prior hydroxyurea for control of
leukocytosis or use of hematopoietic growth factors (eg, G-CSF, GM-CSF, procrit,
aranesp, thrombopoietins) is allowed at any time prior to or during study if
considered to be in the best interest of the patient.

11. Psychiatric illness or social situation that would limit the patient's ability to
comply with study requirements.

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Number of Participants with Complete Response (CR)

Outcome Description:

Complete Response Criteria (CR must last for at least 4 weeks): Marrow: /= 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.

Outcome Time Frame:

4 weeks after first cycle

Safety Issue:


Principal Investigator

Stefan Faderl, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

UT MD Anderson Cancer Center


United States: Institutional Review Board

Study ID:




Start Date:

November 2011

Completion Date:

Related Keywords:

  • Leukemia
  • Myeloproliferative Diseases
  • Leukemia
  • Myeloproliferative Diseases
  • Myelodysplastic Syndrome
  • (MDS)
  • Relapsing
  • Refractory
  • Clofarabine
  • Clofarex
  • Clolar
  • Cytarabine
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride
  • Leukemia
  • Myelodysplastic Syndromes
  • Preleukemia
  • Myeloproliferative Disorders



UT MD Anderson Cancer Center Houston, Texas  77030