5 Day Versus 7 Day Azacitidine in Lower Risk Myelodysplastic Syndrome

NCT01652781 | Unknown Phase 2 DMC

• 1 other identifier: VZ-MDS-PI-0267
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 3

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.

Conditions

Myelodysplastic Syndrome

Keywords

myelodysplastic syndrome; azacitidine; dosing schedule

Outcome Measures

Primary Outcomes (1)

• Overall response rate by modified IWG 2006 response criteria

  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.

  After 6 cycles of treatment up to 25-49 weeks

Secondary Outcomes (2)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  After each course of treatment up to 25-49 weeks

• Cytogenetic response rate by IWG 2006 response criteria

  After 6 cycles of treatment up to 25-49 weeks

Study Arms (2)

5-day arm

EXPERIMENTAL

azacitidine 75mg/m2 subcutaneously for 7 days every 28 days + best supportive care

Drug: Azacitidine

7-day arm

ACTIVE COMPARATOR

azacitidine 75mg/m2 subcutaneously for 5 days every 28 days + best supportive care

Drug: Azacitidine

Interventions

Azacitidine DRUG

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

Also known as: vidaza

5-day arm; 7-day arm

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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)

Sponsors & Collaborators

• Seoul St. Mary's Hospital: lead
• Celgene Corporation: collaborator

Study Sites (3)

Seoul St. Mary's Hospital

Seoul, 137-701, South Korea

RECRUITING

Asan Medical Center

Seoul, South Korea

RECRUITING

Seoul National University Hospital

Seoul, South Korea

RECRUITING

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Azacitidine

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Yoo-Jin Kim, MD, PhD

  Division of hematology, Department of Internal Medicine, Catholic Blood and Marrow Transplantation Center, Seoul St. Mary's Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yoo-Jin Kim, MD, PhD

CONTACT

82-2-2258-6057; yoojink@catholic.ac.kr

Kyungmin Kim

CONTACT

82-2-2258-7926; ddok9765@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: July 11, 2012
• First Posted: July 30, 2012
• Study Start: March 1, 2012
• Primary Completion: June 1, 2016
• Study Completion: December 1, 2016
• Last Updated: November 20, 2015

Record last verified: 2015-11

Locations

KR (3)