Evaluation of Azacitidine in Transfusion Dependent Patients With Low-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML)

Myelodysplastic Syndrome Clinical Trial

Official title:

Clinical and Biological Evaluation of Azacitidine in Transfusion-dependent Patients With Low and Intermediate-1 Risk MDS, and Low-risk CMML, Who Are Either Refractory to or Not Eligible for Treatment With Erythropoietin +/- G-CSF

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01048034
• Other study ID #: NMDSG08A
• Secondary ID: 2009-011483-11
• Status: Completed
• Phase: Phase 2
• First received: January 12, 2010
• Last updated: October 28, 2013
• Start date: January 2010
• Est. completion date: August 2012

Study information

• Verified date: October 2013
• Source: Nordic MDS Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Medical Products Agency
• Study type: Interventional

Clinical Trial Summary

Azacitidine has proved prolonged overall survival in patients with high-risk MDS. Minor pilot studies have shown that treatment with Azacitidine can induce transfusion independency in previous transfusion dependent patients with low-risk MDS. This study will evaluate the effect of Azacitidine in transfusion dependent patients with low-risk MDS (IPSS low or int-1) or low risk CMML. Included patients should first have failed, or considered not being eligible to, treatment with EPO +/- G-CSF. Our hypothesis is that Azacitidine can lead to transfusion independency in this group of patients. Those patients who do not respond to treatment with Azacitidine alone, will be given treatment with the combination of Azacitidine and EPO where our hypothesis is that Azacitidine can restore sensitivity to EPO.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 2012
• Est. primary completion date: August 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Must be 18 years of age at the time of signing the informed consent form

• MDS at IPSS Low or Int-1, or mixed MDS/MPD; either CMML with < 10% marrow blasts or RARS-T

• Patients with high or intermediate probability for response according to the predictive model (see Hellstrom-Lindberg et al, Br J Haematol 99:344-51 1997)should be refractory to EPO / darbepoetin (equivalent to > 60 000 U of EPO / week for > 8 weeks) followed by EPO + G-CSF for > 8 weeks, or biosimilar drugs in equipotent doses, or EPO + G-CSF upfront for 8 weeks. Patients with low probability for response according to the predictive model, could be included without prior EPO/G-CSF treatment

• Transfusion need >4 units over the last 8 weeks, or >8 units over the last 26 weeks.

• Subject has signed the informed consent document.

• Men and women of childbearing potential must use effective contraception during, and for up to 3 months after treatment.

Exclusion Criteria:

• Pregnant or lactating females.

• Patients who are eligible for curative treatment

• Expected survival less than 24 weeks.

• Symptomatic thrombocytopenia / active bleeding

• Patients with JAK-2 positive RARS-T if eligible for new investigational drugs

• Serum biochemical values as follows

1. Serum creatinine >2.0 mg/dL (177 micromol/L)

2. Serum aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) or alanine transaminase (ALT)/serum glutamate pyruvate transaminase (SGPT) >3.0 x upper limit of normal (ULN)

3. Serum total bilirubin >1.5 mg/dL (26 micromol/L)

• Uncontrolled systemic infection

• Considered not capable of following the study protocol

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Myelomonocytic Leukemia
• Leukemia, Myelomonocytic, Acute
• Leukemia, Myelomonocytic, Chronic
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Preleukemia

Intervention

Drug:
• Azacitidine
100 mg / m(2) subcutaneously day 1-5 every 4 weeks for 6 cycles. Another three cycles will be given together with epo for those not responding to the first 6 cycles of Azacitidine
• Erythropoetin
For those patients not responding to Azacitidine alone, the combination of Azacitidine and erythropoetin 60 000 U / week for 16 weeks will be given.

Locations

Country	Name	City	State
Denmark	Department of Hematology, Aalborg University Hospital	Aalborg
Denmark	Department of Hematology, Aarhus Univsersity Hospital	Aarhus
Denmark	Department of Hematology, Rigshospitalet Univsersity Hospital	Copenhagen
Denmark	Department of Hematology, Herlev Hospital	Herlev
Denmark	Department of Hematology, Odense University Hospital	Odense
Norway	Department of Medcine, Haukeland University Hospital	Bergen
Norway	Department of Hematology, Rikshospitalet University Hospital	Oslo
Sweden	Department of Medicine, Mälarsjukhuset Hospital	Eskilstuna
Sweden	Department of medicine, Falun Hospital	Falun
Sweden	Department of Medicine, Sahlgrenska University Hospital / Östra	Göteborg
Sweden	Department of Hematology, Linköping University Hospital	Linköping
Sweden	Department of Medicine, Sunderbyn Hospital	Luleå
Sweden	Department of Hematology, Lund University Hospital	Lund
Sweden	Department of Hematology, Karolinska University Hospital	Stockholm
Sweden	Department of Medicine, Södersjukhuset Hospital	Stockholm
Sweden	Department of Medicine, Umeå University Hospital	Umeå
Sweden	Department of Medicine, Uppsala University Hospital	Uppsala

Sponsors (1)

Lead Sponsor	Collaborator
Nordic MDS Group

Countries where clinical trial is conducted

Denmark,  Norway,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hemoglobin level		Week 28	Yes
Primary	Number of patients reaching transfusion independency after treatment with Azacitidine		Week 28	No
Secondary	Effect on leucocyte, platelet count		Week 28 and End of Trial	Yes
Secondary	Effect on bone marrow morphology and cytogenetics		Week 28 and End of Trial	Yes
Secondary	Number of patients reaching transfusion independency after treatment with Azacitidine and Epo		End of Trial	No
Secondary	Effect on genetic and epigenetic profile		Week 28	No
Secondary	Hemoglobin level		End of Trial	Yes