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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by M.D. Anderson Cancer Center
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT01444742
First received: September 28, 2011
Last updated: October 8, 2014
Last verified: October 2014
  Purpose

The goal of this clinical research study is to learn if clofarabine when given in combination with cytarabine can help to control MDS after the disease could not be controlled with standard therapy. The safety of this treatment will also be studied.

Clofarabine is designed to interfere with the growth and development of cancer cells.

Cytarabine is designed to insert itself into DNA (the genetic material of cells) of cancer cells and stop the DNA from repairing itself.


Condition Intervention Phase
Leukemia
Myeloproliferative Diseases
Drug: Clofarabine
Drug: Cytarabine
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Number of Participants with Complete Response (CR) [ Time Frame: 4 weeks after first cycle ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Overall Survival (OS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 80
Study Start Date: November 2011
Estimated Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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)

Drug: 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)

Other Names:
  • Clofarex
  • Clolar
Drug: 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)

Other Names:
  • Ara-C
  • Cytosar
  • DepoCyt
  • Cytosine Arabinosine Hydrochloride

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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; see section 8 for details) following at least 4 cycles of either azacitidine or decitabine, or following at least 2 cycles of SGI-110, which were completed within the last 2 years - AND/OR - intolerance to azacitidine, decitabine, or SGI-110 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 </= 2.
  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 study.
  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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01444742

Contacts
Contact: Guillermo Garcia-Manero, MD 713-745-3428

Locations
United States, Texas
University of Texas MD Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Guillermo Garcia-Manero, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01444742     History of Changes
Other Study ID Numbers: 2011-0660, NCI-2011-03436
Study First Received: September 28, 2011
Last Updated: October 8, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Leukemia
Myeloproliferative Diseases
Myelodysplastic Syndrome
(MDS)
Relapsing
Refractory
Clofarabine
Clofarex
Clolar
Cytarabine
Ara-C
Cytosar
DepoCyt
Cytosine Arabinosine Hydrochloride

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Myeloproliferative Disorders
Preleukemia
Syndrome
Bone Marrow Diseases
Disease
Hematologic Diseases
Neoplasms
Neoplasms by Histologic Type
Pathologic Processes
Precancerous Conditions
Clofarabine
Cytarabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014