Multicenter Study to Assess the Efficacy of Decitabine in the Treatment of Chronic Myelomonocytic Leukemia (DECI2009)

A Phase II Multicenter Open-label Study to Assess the Efficacy of Decitabine in the Treatment of Chronic Myelomonocytic Leukemia

The study aims to assess the activity of decitabine in the treatment of CMML.

Study Overview

• Status: Completed
• Conditions: Chronic Myelomonocytic Leukemia
• Intervention / Treatment: Drug: Decitabine

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2

Contacts and Locations

Study Locations

• Italy
  • Alessandria, Italy, 15121
    • Ematologia, Ospedale SS Antonio e Biagio e Cesare Arrigo
  • Ancona, Italy, 60131
    • AOU Ospedali Riuniti di Ancona
  • Bari, Italy, 70124
    • Ematologia AOU Policlinico di Bari
  • Bologna, Italy, 40100
    • Istituto di Ematologia e Oncologia Medica, Policlinico S.Orsola
  • Brescia, Italy, 25100
    • Ematologia - Spedali Civili
  • Cagliari, Italy, 09121
    • Ematologia- Ospedale Businco
  • Campobasso, Italy, 86100
    • Centro di ricerca e formazione ad alta tecnologia nelle Scienze, Università Cattolica
  • Firenze, Italy, 50134
    • Cattedra di Ematologia Policlino Careggi
  • Genova, Italy, 16132
    • Dipartimento Emato-Oncologia AOU San Martino Genova
  • Milano, Italy, 20121
    • Fondazione IRCCS Caà Granda-Ospedale Maggiore policlinico
  • Monza, Italy, 20052
    • Divisione di Ematologia, Ospedale S.Gerardo di Monza
  • Novara, Italy, 28100
    • Divisione di Ematologia, Università Avogadro
  • Orbassano, Italy, 10043
    • Medicina interna II Divisione di Ematologia Ospedale S.Luigi Gonzaga
  • Padova, Italy, 35128
    • Azienda Ospedaliera di Padova
  • Perugia, Italy, 06122
    • Ospedale S.Maria della Misericordia
  • Pesaro, Italy, 61122
    • AOU San Salvatore
  • Reggio Calabria, Italy, 89125
    • AO Bianchi Melacrino Morelli
  • Rionero in Vulture, Italy, 85028
    • IRCCS Centri di riferimento oncologico
  • Roma, Italy, 00183
    • SC Ematologia AOU S.Andrea
  • Torino, Italy, 10126
    • Ematologia 2-Ospedale S.Giovanni Battista
  • Torino, Italy, 10126
    • U.O.Ematologia 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients aged 18 and older
2. CMML diagnosis according to WHO criteria

3. If WBC<=12000/mm3:IPSS High or INT-2

   If WBC>12000/mm3: at least two of the following criteria:

   • Blast cells>5% in the bone marrow
   • Citogenetic abnormality other then t(5;12) (q33;p13)
   • Anemia (Hb<10g/dl)
   • Thrombocytopenia (Plt<100000/mm3)
   • Splenomegaly(>5cm below costal margin)
   • Extramedullary localization
4. Patients untretaed or previously treated with Hydroxyurea or Imatinib or Etoposide given orally or non intensive chemotherapy or intensive chemotherapy given more thann 3 months befor inclusion
5. Performance Status ECOG 0,1 or 2
6. Estimated life expectancy>=6 months

7. Adequate hepatic function:

   • Total bilirubin < 1.5 times upper limit of normal (except moderate unconjugate hyperbilirubinemia due to intra medullary hemolysis)
   • AST and ALT < 3 times limit of normal

8. Adequate renal function:

   • Serum creatinine < 1.5 times limit of normal
   • Creatinine clearance > 30ml/min
9. Informed consent
10. Negative pregnancy test or adequate contraception methods

Exclusion Criteria:

1. Myeloproliferative/myelodisplastic syndome othe than CMML
2. Acute blastic transformation of CMML with bone marrow blast cells>20%
3. Patients eligible for allogenic bone marrow transplantation with identified donor
4. CMML with t(5;12) o PDGFBR rearrangement
5. Intensive chemotherapy given less than 3 months before
6. Previous treatment with hypomethylating agent
7. Age< 18 years old
8. Pregnancy or breastfeeding
9. Performance Status ECOG>2
10. Estimate life expectancy<6 months
11. HIV infection
12. Chronic active hepatitis secondary to HCV or HBV (HBSAq positive)
13. Serious concomitantsystemic disorders, including active bacterial fungal or viral infection, that in the opinion of the investigator, would compromise the safety of the patient and/or his/her ability to complete the study

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: Decitabine; Eligible patients will recieve Dacogen 20mg/m2 in 1 hour iv infusion for 5 days every 28 days (1 cycle)plus Best Supportive Care.A total of 6 courses is planned.	Drug: Decitabine; Decitabine will be administered at a dose of 20 mg/m2 infused over a 1 hour period once daily for 5 consecutive days. The totale amount per course is 100 mg/m2. Cycles will be administered every 4 weeks (1 cycle of 28 days).It is recommented that patients be treated for a minimum of 4 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To assess the activity of decitabine in the treatment of CMML	Activity will be evaluated as percentage of patients achieving complete or partial remission according to the International Working Group response criteria in myelodysplasia	24 months

Secondary Outcome Measures

Outcome Measure	Time Frame
to assess the activity of decitabine in the treatment of CMML in terms of overall survival, time to leukemic transormation, response duration in terms of time to relapse after CR, PR, time to disease progression, ecc	24 months

Collaborators and Investigators

• Sponsor: Fondazione Italiana Sindromi Mielodisplastiche-ETS
• Collaborators: Centro di Riferimento per l'Epidemiologia e la Prev. Oncologica Piemonte
• Investigators: Principal Investigator: Santini Valeria, Professor, U.O di Ematologia, AO of Careggi, viale Morgagni n.85-50134-Firenze

Study record dates

Study Major Dates

• Study Start: April 1, 2010
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): June 1, 2018

Study Registration Dates

• First Submitted: December 1, 2010
• First Submitted That Met QC Criteria: December 1, 2010
• First Posted (Estimate): December 2, 2010

Study Record Updates

• Last Update Posted (Actual): June 25, 2018
• Last Update Submitted That Met QC Criteria: June 21, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, Decitabine
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid; Leukemia; Leukemia, Myelomonocytic, Acute; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: DECI2009-AISSM06