The Efficacy and Safety of Oral Azacitidine Plus Best Supportive Care Versus Placebo and Best Supportive Care in Subjects With Red Blood Cell (RBC) Transfusion-Dependent Anemia and Thrombocytopenia Due to International Prognostic Scoring System (IPSS) Low Risk Myelodysplastic Syndrome (MDS)

Celgene

Status and phase: Completed; Phase 3

Conditions: Myelodysplastic Syndrome

Treatments: Drug: Placebo; Other: Best Supportiv Care (BSC); Drug: Oral Azacitidine

Study type: Interventional

Funder types: Industry

Identifiers

NCT01566695

AZA-MDS-003

2012-002471-34 (EudraCT Number)

Details and patient eligibility

About

Evaluation of the Efficacy and Safety of Oral Azacitidine plus Best Supportive care versus Placebo and Best Supportive care in subjects with red blood cell (RBC) transfusion-dependent anemia and thrombocytopenia due to International Prognostic Scoring System (IPSS) lower risk myelodysplastic syndromes (MDS).

Enrollment: 216 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• 18 years or older
• Have a documented diagnosis of MDS
• Anemia that requires red blood cell transfusions
• Thrombocytopenia (sustained for at least 21 days) within 14 days prior to randomization
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2
• Must agree to follow pregnancy precautions as required by protocol.
• Understand and voluntarily sign an informed consent document prior to any study related assessments/procedures being conducted

Exclusion criteria

• Secondary or hypoplastic MDS or other subtype with eligibility for treatment with immunotherapy
• Prior treatment with azacitidine, decitabine, other hypomethylating agents and lenalidomide (for lenalidomide : unless the last dose received is >= 8 weeks prior to inclusion into the study).
• Prior allogeneic or autologous stem cell transplant
• Eligible for allogenic or autologous stem cell transplant
• History of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis), celiac disease (ie, sprue), prior gastrectomy or upper bowel removal, or any other gastrointestinal disorder or defect
• Thrombocytopenia secondary to other possible causes, including medication(s), congenital disorder(s), immune disorder(s), or microvascular disorder(s)
• Use of cytotoxic, chemotherapeutic, targeted or investigational agents/therapies, thrombopoiesis-stimulating agents (TSAs), erythropoiesis-stimulating agents (ESAs) and other red blood cell hematopoietic growth factors, and within 28 days prior to randomization
• Ongoing medically significant adverse events from previous treatment, regardless of the time period
• Concurrent use of iron-chelating agents, (except for subjects on a stable or decreasing dose for at least 8 weeks (56 days) prior to randomization), corticosteroid (except for subjects on a stable or decreasing dose for ≥ 1 week prior to randomization for medical conditions other than MDS)
• Prior history of cancer, other than MDS, unless the subject has been free of the disease for ≥ 3 years. (Basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, carcinoma in situ of the breast, and incidental histologic finding of prostate cancer) (T1a or T1b using the tumor, nodes, metastasis [TNM] clinical staging system is allowed)
• Significant active cardiac disease within the previous 6 months
• Uncontrolled systemic fungal, bacterial, or viral infection
• Known Human Immunodeficiency Virus (HIV) or Hepatitis C (HCV) infection, or evidence of active Hepatitis B Virus (HBV) infection
• Known clinically significant anemia due to iron, vitamin B12, or folate deficiencies, or autoimmune or hereditary hemolytic anemia, or gastrointestinal bleeding
• Abnormal coagulation parameters
• Abnormal liver function test results
• Abnormal kidney function test results
• Known or suspected hypersensitivity to azacitidine or mannitol
• Any significant medical condition, laboratory abnormality, or psychiatric illness

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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216 participants in 2 patient groups, including a placebo group

Oral Azacitidine

Experimental group

Description:

Arm 1: Oral azacitidine tablets 300 mg daily (QD) + best supportive care (BSC) on days 1 through 21 of each 28-day treatment cycle.

Treatment:

Drug: Oral Azacitidine

Other: Best Supportiv Care (BSC)

Placebo

Placebo Comparator group

Description:

Arm 2: Identically matching placebo tablets plus best supportive care on days 1 to 21 of each 28-day treatment cycle.

Treatment:

Other: Best Supportiv Care (BSC)

Drug: Placebo