CMML201: A phase 2 study of azacitidine in chronic myelomonocytic leukaemia (CMML) - CMML201

Phase 1

Active, not recruiting

• Conditions: Chronic Myelomonocytic Leukaemia (CMML): Patients with newly diagnosed or previously treated CMML-1 or CMML-2.; MedDRA version: 16.0 Level: PT Classification code 10009018 Term: Chronic myelomonocytic leukaemia System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2008-006349-23-GB
• Lead Sponsor: The Leeds Teaching Hospitals NHS Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-04-16
• Last Update Posted: 2019-12-10

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: Not specified
• Target Recruitment: 30

Inclusion Criteria

Patients with newly diagnosed or previously treated CMML-1 or CMML-2 according to WHO criteria (2008) with the following characteristics are eligibile for this study:

1. All CMML-2 patients are eligible.
2. For patients classified as CMML-1, the following must be present:

• Symptomatic bone marrow failure / myeloproliferation defined as any of the following:
oRed cell transfusion dependence and pre-transfusion Hb <9.0
oSymptomatic anaemia (Hb <11.5g/dl)
oThrombocytopenia <50 x 109/l
oSymptomatic bleeding due to platelet functional defect or DIC/fibrinolysis
oWCC > 50 x 109/l
AND/OR
• Düsseldorf Score intermediate or high (Appendix 4) for proliferative CMML-1 (i.e. WCC > 12 x 109/L)
• IPSS Score of Int-2 or High Risk (Appendix 5) for non-proliferative CMML-1 (i.e. WCC <12 x 109/L)
AND/OR
• Systemic symptoms including weight loss with no alternative explanation (10% of baseline weight within previous 6 months)
• Symptomatic splenomegaly
• Symptomatic extramedullary involvement e.g. skin infiltration, serous effusions

3. Subject is able and willing to sign the Informed Consent Form.
4. Age 18 years or over at the time of signing the informed consent form.
5. WHO performance status of 2 or less than 2 at study entry.
6. Women of childbearing potential (WCBP) must have a negative urine pregnancy test within 7 days prior to start of study drug.
7. WCBP must agree to use at least 2 effective contraceptive methods throughout the study and for 3 months following the date of the last dose of study drug.
8. Men whose partner is a WCBP must use at least 2 effective contraceptive methods throughout the study and for 3 months following the date of the last dose of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 15

Exclusion Criteria

1. CMML with eosinophilia and 5q33 abnormality.
2. Previous chemotherapy for CMML except Hydroxycarbamide.
3. Creatinine concentration > 2 x the institutional upper limit of the normal range within 28 days of registration.
4. Pregnant or lactating females.
5. Use of any other experimental drug or therapy within 28 days of registration.
6. Known hypersensitivity to azacitidine.
7. Known hypersensitivity to mannitol.
8. Other active malignant disease (including basal or squamous cell carcinoma of the skin).
9. Known positive for HIV or infectious hepatitis, type B or C.
10. Active infection.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Timepoint(s) of evaluation of this end point: N/A;<br> Primary end point(s): • To assess the safety and tolerability of azacitidine <br> • To assess the overall response rate<br> ;Main Objective: To assess the safety, tolerability and efficacy of azacitidine in patients with CMML.;<br> Secondary Objective: To assess response of disease to azacitidine, specifically:<br> <br> •Incidence of CR/PR<br> •Haematological improvement<br> •Overall survival<br> •Progression-free survival<br> •Time to AML transformation of CMML<br> •Time to death or AML transformation of CMML<br> •Biological correlates<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): N/A;Timepoint(s) of evaluation of this end point: N/A