Clinical trial NCT01652781: 5 Day Versus 7 Day Azacitidine in Lower Risk Myelodysplastic Syndrome
Official title: A Randomized, Phase II, Comparative Study With a Parallel Control for Evaluating the Efficacy and Safety of 5-day Azacitidine for Patients With Lower-risk Myelodysplastic Syndrome
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Myelodysplastic Syndrome
Keywords: myelodysplastic syndrome
azacitidine
dosing schedule
Lead sponsor: Seoul St. Mary's Hospital
Sponsor class: OTHER
Collaborators: name: Celgene Corporation
First posted: 2012-07-30
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Approved dosing schedule of azacitidine for myelodysplastic syndrome (MDS) is 75 mg/m\^2/day subcutaneous for 7 consecutive days every 28 days, which is based on the data from standard chemotherapy regimen and a Phase I safety clinical trial. Since the optimal dosage of this drug has not been found yet, it remains as a subject of clinical study that needs to be examined. If initial toxicity is minimized by developing dosage/regimen that replaces the standard therapy, it will be possible to provide continuous treatment with increased convenience by patients and treating physicians as well as improvement for safety in elderly patients or those with serious cytopenia. In addition, it is expected to lead to a better response by strictly keeping a treatment schedule.

Recent US study showed that 5-day regimen showed similar treatment results, but retrospective data from Spain showed lower response rate in 5-day regimen. Considering the recent circumstances around dosage and schedule of azacitidine in lower risk MDS, a Phase II clinical trial is planned in lower risk MDS patients in order to explore the efficacy in 5-day treatment by comparing prospectively with 7-day standard regimen.

Detailed description: * Using block randomization, subjects of Low or intermediate (INT)-1 patients will be equally allocated to the following two types of regimens.

  1. Group A: azacitidine 75mg/m\^2 subcutaneously for 7 days every 28 days + best supportive care
  2. Group B: azacitidine 75mg/m\^2 subcutaneously for 5 days every 28 days + best supportive care
* The study drug, azacitidine, is provided free of charge by Celgene until disease progression or relapse after response, or intolerable toxicity occurs in clinical study subject, or informed consent is withdrawn.
* No crossover between arms is allowed.
* Dose escalation in this study is not allowed; on the contrary, dose reduction or dose delay is possible based on adverse events and hematologic recovery.

Eligibility criteria: Inclusion Criteria:

* Subjects must satisfy the following criteria in order to be enrolled in this clinical trial: Patients who have been diagnosed with MDS by the FAB criteria and belong to Low or INT-1 risk by the IPSS classification will be enrolled in this study. For the purpose of analysis, chronic myelomonocytic leukemia (CMML) patients with less than 5% of myeloblasts are also classified by the IPSS risk classification. Secondary or treatment-related MDS is allowed, but recurrent or persistent MDS after stem cell is not applicable. The enrolled patients should have anemia (hemoglobin \< 10.0g/dL), transfusion dependence, thrombocytopenia (less than 100×10\^9/L), or absolute neutrophil count less than 1.80×10\^9/L.
* 18 years of age or older
* Life expectancy of at least 12 months
* ECOG performance status 2 or less
* Serum creatinine less than 1.5 times the upper limit of normal (ULN) level of the investigating institution
* Serum bilirubin less than 2.0 times the upper limit of normal (ULN) level of the investigating institution
* AST, ALT, and alkaline phosphatase less than 3 times the upper limit of normal (ULN) level of the investigation institution
* Patients who can have informed consent and signed the informed consent form
* Male patients who have a female partner of childbearing potential must agree to use two types of effective contraceptive methods during the study and for 30 days following the last dose.
* Females of childbearing potential (FCBP) must satisfy the following criteria: must agree to use the contraceptive method (oral contraceptives, injectables, hormonal implants; tubal ligation; intra uterine device; spermicidal contraceptives, the sterilized partner) approved by the physician during azacitidine treatment and for 3 months following the last dose, and must have a negative result of serum pregnancy test that was performed within 72 hours prior to starting study drug therapy.

Exclusion Criteria:

* Any coexisting major illness or organ failure
* HIV positive, or active hepatitis B or C infection
* Uncontrolled acute infection
* Uncontrolled hemorrhage
* Pregnant or lactating
* Known or suspected hypersensitivity to azacitidine
* Patients diagnosed with malignant hepatic carcinoma or malignant disease within the past 12 months (except in situ carcinoma without complication, cervical or breast intraepithelial neoplasia, or other local malignant carcinoma that is likely to be treated by surgical removal or radiotherapy)

Primary outcomes:
measure: Overall response rate by modified IWG 2006 response criteria
timeFrame: After 6 cycles of treatment up to 25-49 weeks
Secondary outcomes:
measure: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
timeFrame: After each course of treatment up to 25-49 weeks
measure: Cytogenetic response rate by IWG 2006 response criteria
timeFrame: After 6 cycles of treatment up to 25-49 weeks
Other outcomes:
Locations:
city: Seoul
country: Korea, Republic of
facility: Seoul St. Mary's Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
Study officials:
affiliation: Division of hematology, Department of Internal Medicine, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital
name: Yoo-Jin Kim, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: