Study of Clofarabine in Combination With Low Dose Cytarabine to Treat Myelodysplastic Syndromes (CLO2009AISSM05)

Phase II Study of Clofarabine in Combination With Low Dose Cytarabine for Untreated Patients With Poor Risk Myelodysplastic Syndromes

This is an interventional, multicenter, open label, phase II study designed to evaluate the safety and efficacy of Clofarabine in combination with low dose Cytarabine in untreated patients with poor risk of Myelodisplastic Syndromes.

Study Overview

• Status: Withdrawn
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Clofarabine plus low dose Ara-C

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Alessandria, Italy, 15121
    • SC Ematologia-AO SS.Antonio e Biagio e Cesare Arrigo
  • Ancona, Italy, 60020
    • Dipartimento Scienze Mediche e Chirurgiche-Ospedale di Torrette
  • Bari, Italy, 70124
    • Ematologia con trapianto-AO Policlinico Bari
  • Brescia, Italy, 25123
    • SC di Ematologia-Spedali Civili
  • Campobasso, Italy, 86100
    • centro di ricerca e di formazione ad alta tecnologia nelle Scienze-Università Cattolica Campobasso
  • Catania, Italy, 95123
    • Ematologia e Trapianto di Midollo Osseo-Ospedale Ferrarotto Alessi
  • Genova, Italy, 16132
    • Dipartimento di medicina Interna-Università di genova
  • Lecce, Italy, 73100
    • UO Ematologia Vito Fazzi
  • Messina, Italy, 98158
    • SC Ematologia-Azienda Ospedaliero Papardo
  • Napoli, Italy, 80131
    • UO Ematologia-Ospedale San gennaro-ASL1
  • Napoli, Italy
    • Divisione di Ematologia e Trapianto Cellule Staminali-Ospedale A.Cardelli
  • Orbassano, Italy, 10043
    • Medicina interna II- Azienda Ospedaliera S.Luigi Gonzaga
  • Palermo, Italy, 90146
    • Divisione di Ematologia-Ospedale Vincenzo Cervello
  • Pescara, Italy, 65100
    • Dipartimento di Ematologia-Ospedale Spirito Santo Pescara
  • Pisa, Italy, 56100
    • Divisione di Ematologia- Azienda Ospedaliera Pisana Ospedale "S.Chiara"
  • Reggio Calabria, Italy, 89100
    • Divisione Ematologia- AO Bianchi Melacrino Morelli
  • Rionero in Vulture, Italy, 85028
    • UO Ematologia e Trapianto Cellule Staminali, IRCCS, Centro di Riferimento Oncologico della Basilicata
  • Roma, Italy, 00189
    • Ematologia-Azienda Ospedaliera Sant'Andrea
  • San Giovanni Rotondo, Italy, 71013
    • Divisione di Ematologia, Centro Trapianto di cellule staminali-IRCCS "Casa Sollievo della Sofferenza"
  • Torino, Italy, 10126
    • UO Ematologia 2-Ospedale San Giovanni Battista
  • Tricase, Italy, 73039
    • Divisione di Ematologia-Ospedale Cardinale Panico

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male and female patients age 55 to 80 years
• Written informed consent to participate in the clinical trial
• Morphologically confirmed diagnosis of MDS according to WHO classification, and IPSS INT-2 or high risk according to IPSS index
• ECOG performance status 0-2
• No previous chemotherapy
• Serum bilirubin ≤1.5 times upper limit of normal (ULN) (unless elevation is due primarily to elevated unconjugated hyperbilirubinemia secondary to Gilbert's syndrome or hemolysis, but not to liver dysfunction)
• AST and ALT ≤2.5 times ULN
• Alkaline phosphatase ≤2.5 times ULN
• Serum creatinine ≤ 1 mg/dl: if serum creatinine > 1.0 mg/dl, then the estimated glomerular filtration rate (GFR) must be >60 mL/min/1.73 m2 as calculated by the Modification of Diet in Renal Disease equation where Predicted GFR (ml/min/1.73 m2) = 186 x (Serum Creatinine) -1.154 x age in years -0-023 x 0.742 (if patient is female) x 1.212 (if patient is black)
• HIV negative

Exclusion Criteria:

• Have had any other chemotherapy or any investigational therapy as a treatment for MDS. Patients who received chemotherapy for other cancers than MDS/AML can be enrolled, provided that at least 6 months elapsed from accomplishment of the last course of chemo.
• Have had a prior hematopoietic stem cell transplant for MDS
• Have an uncontrolled systemic fungal, bacterial, viral, or other infection (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
• Have a psychiatric disorder that would interfere with consent, study participation, or follow-up.
• Have any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart
• Have had any prior treatment with Clofarabine
• Have had a diagnosis of another malignancy, unless the patient has been disease-free for at least 3 years following the completion of curative intent therapy with the following exceptions: a.)Patients with treated non-melanoma skin cancer, in situ carcinoma, or cervical intraepithelial neoplasia, regardless of the disease -free duration, are eligible for this study if definitive treatment for the condition has been completed. b.)Patients with organ-confined prostate cancer with no evidence of recurrent or progressive disease based on prostate-specific antigen (PSA) values are also eligible for this study if hormonal therapy has been initiated or a radical prostatectomy has been performed.
• Have prior positive test for the Human Immunodeficiency Virus (HIV), HCV, HBV.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm 1; Clofarabine combined with low dose Ara-C	Drug: Clofarabine plus low dose Ara-C; Clofarabine 10 mg/m2 by a 1-hr i.v infusion, once daily, from day 1 to 5. Ara-C 10 mg/m2, subcutaneously, twice a day (q12 hrs), from day 1 to 15. Clofarabine will be given 4 hours before the 2nd dose of Ara-C.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
To assess the remission rate according to the combination regimen	19 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of response and survival	19 months
Time to transformation in AML	19 months
To determine the relationship of cytogenetic abnormalities and response to treatment	19 months
To determine the safety and tolerability of the combination regimen	19 months

Collaborators and Investigators

• Sponsor: Fondazione Italiana Sindromi Mielodisplastiche-ETS
• Investigators: Study Chair: Felicetto Ferrara, MD, Division of Hematology and Stem Cell Transplantation Unit, Ospedale "A.Cardarelli", Napoli, Italy

Study record dates

Study Registration Dates

• First Submitted: December 22, 2010
• First Submitted That Met QC Criteria: February 21, 2011
• First Posted (Estimate): February 23, 2011

Study Record Updates

• Last Update Posted (Estimate): October 1, 2013
• Last Update Submitted That Met QC Criteria: September 30, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Myelodysplastic Syndromes; Clofarabine; Low Dose Cytarabine; Poor risk MDS
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Clofarabine
• Other Study ID Numbers: CLO2009AISSM05; EudraCT number 2009-012755-23