Phase I/II Study of 5-Azacytidine With Ara-C in Patients With Relapsed/Refractory Acute Myelogenous Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)
Randomized Phase I/II Study of 5-Azacytidine in Combination With Cytosine Arabinoside in Patients With Relapsed/Refractory Acute Myelogenous Leukemia or High Risk Myelodysplastic Syndrome - "SPORE"
1 other identifier
interventional
36
1 country
1
Brief Summary
The goal of this clinical research study is to find the highest tolerable dose of Azacytidine (5-azacytidine) combined with cytosine arabinoside (ara-C) for the treatment of patients with relapsed and/or refractory Acute Myeloid Leukemia (AML) or high-risk Myelodysplastic Syndrome (MDS). The safety and effectiveness of this treatment combination will also be studied.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Dec 2005
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 2005
CompletedFirst Submitted
Initial submission to the registry
December 5, 2007
CompletedFirst Posted
Study publicly available on registry
December 6, 2007
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 1, 2009
CompletedStudy Completion
Last participant's last visit for all outcomes
October 1, 2009
CompletedResults Posted
Study results publicly available
February 14, 2011
CompletedAugust 1, 2012
July 1, 2012
3.8 years
December 5, 2007
January 21, 2011
July 26, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Number of Participants With Complete Remission
Clinical response is determined by achievement of a complete remission (CR) as judged by morphological criteria (\< 1% blasts in bone marrow with neutrophil recovery) according to International Working Group (IWG) criteria.
6 weeks
Study Arms (4)
Low-Dose Ara-C + AZA-Level 0
EXPERIMENTALGroup 1 = Low-Dose Ara-C + Azacitidine-Level 0 Low-Dose Ara-C: 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days Azacitidine (AZA): 37.5 mg/m\^2 intravenous (IV) Over 20-30 minutes Daily for 7 Days
Low-Dose Ara-C + AZA-Level 1
EXPERIMENTALGroup 2 = Low-Dose Ara-C + Azacitidine-Level 1 Low-Dose Ara-C: 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days AZA: Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days
High-Dose Ara-C + AZA-Level 0
EXPERIMENTALGroup 3 = High-Dose Ara-C + Azacitidine-Level 0 High-dose Ara-C: 1 g/m\^2 Daily CIV for 4 days (age\<65years) or 3 days (age\>=65years) AZA: 37.5 mg/m\^2 IV Over 20-30 minutes Daily for 7 Days
High-Dose Ara-C + AZA-Level 1
EXPERIMENTALGroup 4 = High-Dose Ara-C + Azacitidine-Level 1 High-dose Ara-C: 1 g/m\^2 Daily CIV for 4 days (age\<65years) or 3 days (age\>=65 years) AZA:Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days
Interventions
Group 1 and 3 at Level 0 = 37.5 mg/m\^2 IV Over 20-30 minutes Daily for 7 Days Group 2 and 4 at Level 1 = 75.0 mg/m\^2 IV Over 20-30 minutes Daily for 7 days
Group 1 and 2 at Low-Dose = 100 mg/m\^2 Daily continuous intravenous infusion (CIV) for 7 days Arms 3 and 4 at High-dose = 1 g/m\^2 Daily CIV for 4 days (age\<65 years) or 3 days (age\>=65 years)
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed Acute Myeloid Leukemia (AML) or high risk and previously treated Myelodysplastic Syndrome (MDS).
- Patients with (1) refractory disease or (2) first relapse within 6 months of therapy or (3) 2nd or more of relapse of Acute Myelogenous Leukemia (AML) or high risk Myelodysplastic Syndrome MDS will be considered for the study.
- Patients must have been off chemotherapy for 4 weeks prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease.
- Age \>=18 years. Deoxyribonucleic acid (DNA) methylation plays a significant role in development, and the effects of azacitidine in children are not well described.
- Patients must have normal organ as defined: Total bilirubin \<2 mg, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) \<2.5 x institutional upper limit of normal, Creatinine \<2 mg
- Ability to understand and the willingness to sign a written informed consent document.
- Women of child bearing potential must have a negative serum pregnancy test prior to azacitidine treatment.
- Women of child bearing potential should be advised to avoid becoming pregnant and men should be advised to not father a child while receiving treatment with azacytidine.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
You may not qualify if:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier, unless there is evidence of rapidly progressive disease. Patients may have received hydroxyurea prior to entering the study.
- Patients may not be receiving any other investigational agents for their leukemias.
- Patients with active brain or meningeal disease should be excluded.
- Known or suspected hypersensitivity to azacitidine or mannitol
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements.
- Pregnant women are excluded from this study because azacitidine is a Deoxyribonucleic acid (DNA) methyltransferase inhibitor which has teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with azacitidine, breastfeeding should be discontinued if the mother is treated with azacitidine.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- M.D. Anderson Cancer Centerlead
- Celgene Corporationcollaborator
Study Sites (1)
U.T.M.D. Anderson Cancer Center
Houston, Texas, 77030, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Jean-Pierre Issa, M.D./Professor
- Organization
- The University of MD Anderson Cancer Center
Study Officials
- PRINCIPAL INVESTIGATOR
Jean-Pierre Issa, MD
M.D. Anderson Cancer Center
Publication Agreements
- PI is Sponsor Employee
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 5, 2007
First Posted
December 6, 2007
Study Start
December 1, 2005
Primary Completion
October 1, 2009
Study Completion
October 1, 2009
Last Updated
August 1, 2012
Results First Posted
February 14, 2011
Record last verified: 2012-07