Use of Decitabine in Myelodysplastic Syndrome (MDS) Following Azacitidine (AZA) Failure (DEC-MDS)

The purpose of this study is to assess the response rate at 6 months in Myelodysplastic Syndrome (MDS) patients, Chronic Myelomonocytic Leukaemia (CMML-2) patients, and Acute Myeloid Leukaemia (AML) patients with up to 30% bone marrow blasts, treated with low-dose decitabine who have previously failed therapy with 5-azacitidine.

Study Overview

• Status: Unknown
• Conditions: Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome
• Intervention / Treatment: Drug: Decitabine

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • King's College Hospital NHS Foundation Trust
    • Contact: Ghulam J Mufti, MB, DM, FRCP, FRCPath; Phone Number: 3238 +44 (0) 20 3299 9000; Email: ghulam.mufti@kcl.ac.uk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Written signed informed consent.
2. ≥18 years of age.
3. Diagnosed MDS with 5% or more marrow blasts and IPSS risk intermediate 2 or high risk; or chronic myelomonocytic leukemia (CMML-2); or AML with 20-30% bone marrow blasts.
4. Patients who have failed therapy with azacitidine.
5. Performance status 0-2 (ECOG scale).
6. Adequate hepatic (bilirubin < 1.5 X ULN or AST< 2.5 X ULN) and renal functions (creatinine <1.5 X ULN).

Exclusion Criteria:

1. Nursing and pregnant females.
2. Females of childbearing potential and males not willing to practice an effective method of contraception whilst receiving decitabine and for 2 months after the last infusion.
3. Patients with previous malignancy or concurrent malignancy.
4. Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure and unstable angina pectoris.
5. Ongoing oral corticosteroids are not permitted. However, use of corticosteroids (topical and inhaled) is permitted and prophylactic steroids are allowed for transfusion reactions.
6. Patients who have received any investigational agent within the 30 days preceding the first dose of study drug.
7. Patients who have received prior intensive combination chemotherapy or high-dose cytarabine (>/= 1g/m*2 per dose). (Prior biologic therapies, targeted therapies and single agent chemotherapy are allowed).
8. Patients who have an active viral or bacterial infection. Note: No patient is allowed to enter the study unless infections have been fully treated and the patient has remained afebrile for 7 days without antibiotics.
9. Patients who have concurrent autoimmune hemolytic anemia or immune thrombocytopenia.
10. Patients who have previously been treated with decitabine.
11. Patients who have known positive serology for HIV.
12. Patients with a condition that may be unable to comply with the treatment and monitoring requirements of 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	Drug: Decitabine; Patients will receive decitabine as a 20mg/m2 one hour intravenous infusion once daily on days 1 to 5 of a 4 week cycle.; Other Names: Dacogen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall response rate in the efficacy-evaluable (EE) population	6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall survival	18 months
Time to AML progression (for MDS and CMML-2 patients only) or death	18 months
Haematological improvement	18 months
Transfusion requirements	18 months
Cytogenetic response	18 months
Treatment related toxicity	Up until one month after last IMP dose

Collaborators and Investigators

• Sponsor: King's College London
• Collaborators: King's College Hospital NHS Trust

Study record dates

Study Major Dates

• Study Start: September 1, 2010
• Primary Completion (Anticipated): September 1, 2012
• Study Completion (Anticipated): September 1, 2013

Study Registration Dates

• First Submitted: May 28, 2010
• First Submitted That Met QC Criteria: May 28, 2010
• First Posted (Estimate): May 31, 2010

Study Record Updates

• Last Update Posted (Estimate): September 3, 2010
• Last Update Submitted That Met QC Criteria: September 2, 2010
• Last Verified: September 1, 2010

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic-Myeloproliferative Diseases; Leukemia, Myeloid; Syndrome; Myelodysplastic Syndromes; Leukemia; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine
• Other Study ID Numbers: DEC-MDS