5 Day Versus 7 Day Azacitidine in Lower Risk Myelodysplastic Syndrome

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2012 by Seoul St. Mary's Hospital.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Celgene Corporation
Information provided by (Responsible Party):
Yoo-Jin Kim, Seoul St. Mary's Hospital
ClinicalTrials.gov Identifier:
NCT01652781
First received: July 11, 2012
Last updated: July 25, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Myelodysplastic Syndrome
Drug: Azacitidine
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Seoul St. Mary's Hospital:

Primary Outcome Measures:
  • Overall response rate by modified IWG 2006 response criteria [ Time Frame: After 6 cycles of treatment up to 25-49 weeks ] [ Designated as safety issue: No ]
    Overall response rate is evaluated by assessing the percentage of patients with response (complete remission (CR), partial remission (PR), bone marrow CR, and hematologic improvement), response period, and transfusion requirement. Best response during at least 6 cycles of treatment will be assessed if there is no treatment failure or disease progression within 6 cycles of treatment. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 49 weeks the maximum Time Frame.


Secondary Outcome Measures:
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: After each course of treatment up to 25-49 weeks ] [ Designated as safety issue: Yes ]
    •Safety and tolerability profile of 5-day azacitidine in comparison with 7-day regimen. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 49 weeks the maximum Time Frame.

  • Cytogenetic response rate by IWG 2006 response criteria [ Time Frame: After 6 cycles of treatment up to 25-49 weeks ] [ Designated as safety issue: Yes ]
    •Cytogenetic response of of 5-day azacitidine in comparison with 7-day regimen. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 49 weeks the maximum Time Frame.


Estimated Enrollment: 92
Study Start Date: March 2012
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: February 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 5-day arm
azacitidine 75mg/m2 subcutaneously for 7 days every 28 days + best supportive care
Drug: Azacitidine
5-day arm: azacitidine 75mg/m2 subcutaneously for 7 days every 28 days + best supportive care 7-day arm: azacitidine 75mg/m2 subcutaneously for 5 days every 28 days + best supportive care
Other Name: vidaza
Active Comparator: 7-day arm
azacitidine 75mg/m2 subcutaneously for 5 days every 28 days + best supportive care
Drug: Azacitidine
5-day arm: azacitidine 75mg/m2 subcutaneously for 7 days every 28 days + best supportive care 7-day arm: azacitidine 75mg/m2 subcutaneously for 5 days every 28 days + best supportive care
Other Name: vidaza

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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01652781

Contacts
Contact: Yoo-Jin Kim, MD, PhD 82-2-2258-6057 yoojink@catholic.ac.kr
Contact: ChungIn Lee 82-2-2258-7926 qodsucnd@gmail.com

Locations
Korea, Republic of
Seoul St. Mary's Hospital Recruiting
Seoul, Korea, Republic of, 137-701
Contact: Yoo-Jin Kim, MD, PhD    82-2-2258-6057    yoojink@catholic.ac.kr   
Contact: ChungIn Lee    82-2-2258-7926    qodsucnd@gmail.com   
Seoul National University Hospital Recruiting
Seoul, Korea, Republic of
Contact: Sung Soo Yoon, MD, PhD         
Asan Medical Center Recruiting
Seoul, Korea, Republic of
Contact: Je Hwan Lee, MD, PhD         
Samsung Medical Center Recruiting
Seoul, Korea, Republic of
Contact: Jun Ho Jang, MD, PhD         
Sponsors and Collaborators
Seoul St. Mary's Hospital
Celgene Corporation
Investigators
Principal Investigator: Yoo-Jin Kim, MD, PhD Division of hematology, Department of Internal Medicine, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital
  More Information

No publications provided

Responsible Party: Yoo-Jin Kim, Associate Professor, Seoul St. Mary's Hospital
ClinicalTrials.gov Identifier: NCT01652781     History of Changes
Other Study ID Numbers: VZ-MDS-PI-0267
Study First Received: July 11, 2012
Last Updated: July 25, 2012
Health Authority: Korea: Food and Drug Administration

Keywords provided by Seoul St. Mary's Hospital:
myelodysplastic syndrome
azacitidine
dosing schedule

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Syndrome
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Disease
Pathologic Processes
Azacitidine
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 16, 2014