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

NCT01444742 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 2011-0660NCI-2011-03436
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical research study is to learn if clofarabine when given in combination with cytarabine can help to control myelodysplastic syndrome (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.

Conditions

Leukemia; Myeloproliferative Diseases

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Complete Response (CR)

  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.

  4 weeks after first cycle

Secondary Outcomes (1)

• Overall Survival (OS)

  5 years

Study Arms (1)

Clofarabine + Cytarabine

EXPERIMENTAL

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; Drug: Cytarabine

Interventions

Clofarabine DRUG

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)

Also known as: Clofarex, Clolar

Clofarabine + Cytarabine

Cytarabine DRUG

Induction: 20 mg subcutaneously twice daily for 7 days (days 1-7) Consolidation: 20 mg subcutaneously twice daily for 5 days (days 1-5)

Also known as: Ara-C, Cytosar, DepoCyt, Cytosine Arabinosine Hydrochloride

Clofarabine + Cytarabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \>/= 18 years.
• Diagnosis of MDS confirmed within 10 weeks prior to study entry according to World Health Organization (WHO) or French-American-British (FAB) criteria. Patients are either not eligible for or choose not to proceed with a stem cell transplant.
• MDS classified as follows: refractory anemia with excess blasts (RAEB-1) (5%-9% BM blasts); RAEB-2 (10%-19% BM Blasts); chronic myelomonocytic leukemia (CMML) (5%-19% Bone Marrow (BM) blasts); RAEB-t (20%-29% BM blasts) AND/OR by International Prostate Symptom Score (IPSS): intermediate-2 and high risk patients.
• No response, progression, or relapse (according to 2006 International Working Group (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.
• Eastern Cooperative Oncology Group (ECOG) performance status of \</= 2.
• Willing to adhere to and comply with all prohibitions and restrictions specified in the protocol.
• 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.

You may not qualify if:

• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
• Active infection not adequately responding to appropriate antibiotics (i.e. ongoing temperatures of \>/= 38 degree Celsius).
• 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.
• Alanine transaminase (ALT/SGPT) or aspartate transaminase (AST/SGOT) \>/= 2.5 x the upper limit of normal.
• Serum creatinine \> 1.5 mg/dL.
• Female patients who are pregnant or lactating.
• 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.
• Female patients with reproductive potential who do not have a negative urine or blood beta-human chorionic gonadotropin (beta HCG) pregnancy test at screening.
• Patients receiving any other concurrent investigational agent or chemotherapy, radiotherapy, or immunotherapy.
• No prior treatment with cytarabine or clofarabine. Prior hydroxyurea for control of leukocytosis or use of hematopoietic growth factors (eg, G-CSF, Granulocyte-macrophage colony-stimulating factor (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.
• Psychiatric illness or social situation that would limit the patient's ability to comply with study requirements.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• University of Texas MD Anderson Cancer Center Website

MeSH Terms

Conditions

Leukemia; Myelodysplastic Syndromes; Recurrence

Interventions

Clofarabine; Cytarabine

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Adenine Nucleotides; Purine Nucleotides; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Nucleotides; Ribonucleotides; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Guillermo Garcia-Manero, MD/Professor
• Organization: The University of Texas MD Anderson Cancer Center

CR_Study_Registration@mdanderson.org

713-745-3428

Study Officials

• Guillermo Garcia-Manero, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 28, 2011
• First Posted: October 3, 2011
• Study Start: November 16, 2011
• Primary Completion: January 29, 2017
• Study Completion: January 29, 2017
• Last Updated: July 3, 2018
• Results First Posted: May 31, 2018

Record last verified: 2018-06

Locations

US (1)