Study of Vidaza (Azacitidine) Versus Support Treatment in Patients With Low Risk Myelodysplastic Syndrome (Low and Intermediate-1 IPSS) Without the 5q Deletion and Transfusion Dependent Anaemia

Myelodysplastic Syndrome (MDS) Clinical Trial

— ABRAZA  

Official title:

Multicentre, Open-label, Randomized Phase II Study of Vidaza (Azacitidine) Versus Support Treatment in Patients With Low Risk Myelodysplastic Syndrome (Low and Intermediate-1 International Prognostic Scoring System(IPSS )) Without the 5q Deletion and Transfusion Dependent Anaemia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01338337
• Other study ID #: ABRAZA
• Status: Completed
• Phase: Phase 2
• First received: April 13, 2011
• Last updated: January 25, 2016
• Start date: November 2010
• Est. completion date: December 2015

Study information

• Verified date: January 2016
• Source: Asociación Andaluza de Hematología y Hemoterapia
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Agencia Española de Medicamentos y Productos SanitariosSpain: Comité Ético de Investigación Clínica
• Study type: Interventional

Clinical Trial Summary

Primary Outcome Measures:

• To evaluate the efficacy of treatment with Azacitidine in patients with transfusion-dependent, low risk International Prognostic Scoring System (IPSS) 0 int-1, Myelodysplastic Syndrome (MDS) without chromosome 5 (5q) deletion. The main objective will be based on the erythroid haematologic response according to International Working Group (IWG) 2006 criteria.

Secondary Outcome Measures:

• Haematologic response, bases on the following parameters: platelets, and neutrophils according to International Working Group (IWG) Criteria.

• Medullary and cytogenetic response according to International Working Group (IWG) 2006 criteria.

• The effect of treatment response on quality of life, through the Functional Assessment of Cancer Therapy-Anemia (FACT-an) questionnaire.

• Overall survival, Event-Free Survival and the Acute Leukaemia Transformation Rate.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Patients over 18 years of age.

2. Patients who agree to take part in the study must understand the informed consent and sign it voluntarily.

3. Patients must be able to comply with all the programmed visits and other study requirements.

4. Patients with low risk International Prognostic Scoring System (IPSS 0 or Int-1) myelodysplastic syndrome (MDS) without chromosome 5 (5q) deletion and anaemia with transfusion needs. Transfusion dependence is defined as at least 2 units of erythrocyte concentrate (EC) during the 8 weeks prior to inclusion in the study, and symptomatic anaemia, defined by a haemoglobin value =9.0 gr/dl.

5. Patients who have not responded to previous treatment with erythropoietin (EPO): With a response profile based on basal erythropoietin (EPO) levels of > 250 u/L, with no response alter 12 weeks of treatment at maximum doses (60.000 U or 250 µg darbepoetin (DAB), in combination with Granulocyte colony-stimulating factor (G-CSF) in cases of refractory anaemia with ringed sideroblasts (RARS)) , or with loss of the response obtained after an initial optimum response.

6. Patients who are not candidates for intensive chemotherapy and transplant modalities.

7. Patients with an Eastern Cooperative Oncology Group (ECOG) score = 3

8. Women of child-bearing age and heterosexual men whose partner is of child-bearing age, must undertake to use an effective contraceptive method for the duration of the treatment and for at least 3 months alter is has finalised.

Exclusion Criteria:

1. The presence of a psychiatric or medical disease which prevents the patient from signing of the informed consent.

2. Human immunodeficiency virus (HIV) Seropositive, hepatitis B antigen (AgVHB) positive or hepatitis C virus (HCV) polymerase chain reaction (PCR) positive.

3. Pregnant or nursing women.

4. Uncontrolled intercurrent disease: Active infection requiring parenteral antibiotics, Symptomatic chronic heart failure (New York Heart Association (NYHA) class III or IV), Instable angina pectoris, or Another neoplasia apart from his myelodysplastic syndromes (MDS).

5. Have been treated with demethylating drugs at any moment prior to inclusion in the study.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Anemia
• Myelodysplastic Syndrome (MDS)
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• Azacitidine
Azacitidine 75 mg/m2, for 5 days of each 20 day cycle. Transfusional support will be applied for symptomatic anaemia using clinical discretion and chelation therapy when ferritin is = 1000 µgr/ml with the chelating agents allowed

Locations

Country	Name	City	State
Spain	Hospital Reina Sofía, Servicio de Hematología	Cordoba
Spain	Hospital Universitario San Cecilio	Granada
Spain	Hospital Virgen de las Nieves	Granada
Spain	Hospital Juan Ramón Jiménez	Huelva
Spain	Hospital General de Jerez	Jerez	Cádiz
Spain	Hospital Carlos Haya	Malaga
Spain	Hospital Costa del Sol	Marbella	Malaga
Spain	Hospital Universitario Virgen de Valme	Sevilla
Spain	Hospital Universitario Virgen del Rocío	Sevilla

Sponsors (1)

Lead Sponsor	Collaborator
Asociación Andaluza de Hematología y Hemoterapia

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Erythroid haematologic response	To evaluate the efficacy of treatment with Azacitidine in patients with transfusion-dependent, low risk International Prognostic Scoring System (IPSS) 0 or int-1, Myelodysplastic Syndrome (MDS) without chromosome 5 (5q) deletion. The main objective will be based on the erythroid haematologic response according to International Working Group (IWG) 2006 criteria.	Approximately the primary outcome is measured on days 0, 252 and 504 (basal, cycle 9 and 18 (each cicle has 28 days +/-3 days))	No
Secondary	Haematologic response	Haematologic response, bases on the following parameters: platelets, and neutrophils according to International Working Group (IWG) Criteria.	The secondary outcome is measured on days 0, 28, 56, 84, 112, 140, 168, 196, 224, 252, 280, 308, 336, 364, 392, 420, 448, 476 and 504 (the measurement is performed at basal line and in every cycle (every 28 days +/-3 days) up to a maximum of 18 cycles).	No
Secondary	Medullary and cytogenetic response	Medullary and cytogenetic response according to International Working Group (IWG) 2006 criteria.	Approximately this secondary outcome is measured on days 252 and 504 (basal, cycle 9 and 18 (each cicle has 28 days +/-3 days)).	No
Secondary	Quality of life	The effect of treatment response on quality of life, through the Functional Assessment of Cancer Therapy-Anemia (FACT-An) questionnaire.	Approximately this secondary outcome is measured on days 252 and 504 (basal, cycle 9 and 18 (each cicle has 28 days +/-3 days)).	No
Secondary	Overall survival	Overall survival	The secondary outcome is measured from basal line until day 504 (average of days for 18 cycles), or until progresion, or until exitus... (from basal line until the end of the study)	No
Secondary	Event-Free Survival	Event-Free Survival	The secondary outcome is measured from basal line until day 504 (average of days for 18 cycles), or until progresion, or until exitus... (from basal line until the end of the study)	No
Secondary	Acute Leukaemia Transformation Rate	Acute Leukaemia Transformation Rate	The secondary outcome is measured from basal line until day 504 (average of days for 18 cycles), or until progresion, or until exitus... (from basal line until the end of the study)	No