- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01041443
5-Fluoro-2'-Deoxycytidine and Tetrahydrouridine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes
June 3, 2015 updated by: City of Hope Medical Center
A Phase I Study of 5-Fluoro-2'-Deoxycytidine With Tetrahydrouridine (FdCyd + THU) in Myeloid Leukemia and MDS
This phase I trial is studying the side effects and best dose of 5-Fluoro-2'-deoxycytidine (FdCyd) when given together with tetrahydrouridine (THU) in treating patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS).
FdCyd may inhibit cancer cell growth by increasing the production in cells of compounds that suppress growth or by otherwise killing cells.
Although FdCyd is stable as a drug solution, it is rapidly inactivated by an enzyme present in people.
THU is included in the treatment to inhibit the enzyme, prolonging the time FdCyd remains in the body
Study Overview
Status
Completed
Conditions
Detailed Description
OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of FdCyd administered with a fixed dose of THU in patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS), once daily on days 1-10 of a 21-day treatment cycle.
II.
To describe the toxicities of FdCyd/THU in patients with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS).
III.
To document all clinical responses and hematologic improvement in patients treated with FdCyd/THU.
IV.
To obtain preliminary information regarding the effect of FdCyd/THU on deoxyribonucleic acid (DNA) methylation patterns in peripheral blood mononuclear cells and bone marrow aspirates, including malignant myeloid cells; the ratio of gamma- to beta-globin messenger ribonucleic acid (mRNA) in blood cells; and serum cytokines.
OUTLINE: This is a dose-escalation study of FdCyd.
Patients receive FdCyd intravenously (IV) over 3 hours and THU IV over 3 hours on days 1-10.
Courses repeat every 21days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up for 4 weeks.
Study Type
Interventional
Enrollment (Actual)
25
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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California
-
Duarte, California, United States, 91010
- City of Hope
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
Patients must have the following diagnosis:
Acute myeloid leukemia
- Relapsed or refractory
- Newly diagnosed in patients age 60 and above or of any age unable to receive standard induction regimen
Patients with MDS with an International Prognostic Scoring System (IPSS) score >= 0.5
- Newly diagnosed
- Relapsed or refractory
- Any prior therapy must have been completed >= 2 weeks prior to enrollment and the participant must have recovered to eligibility levels from prior toxicity
- No limit to number of prior regimens
- Hydroxyurea is allowed prior to enrollment to keep white blood cell count (WBC) below 20 K
- Valproic acid not being used for seizure control should be stopped 72 hours before starting therapy
- Prior therapy with hypomethylating agent (decitabine or azacitidine) is allowed and must be completed >= 6 weeks prior to enrollment
- Relapsed patients are eligible post allogeneic or matched unrelated donor (MUD) transplant after 100 days; there should be no active acute graft versus host disease of any grade and patient should not be receiving immunosuppression for acute graft versus host disease; the patient must not have Chronic Graft versus Host disease (cGvHD) other than mild skin, oral, or ocular cGvHD not requiring systemic immunosuppression
- Relapsed patients are eligible post autologous transplant after 100 days post transplant, with recovery of their counts absolute neutrophil count (ANC) > 1000 and platelets greater than 75K at some point post transplant
- Karnofsky performance status >= 60%
- Total bilirubin < 1.5 x institutional upper limit of normal
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase [SGPT]) =< 2.5 x institutional upper limit of normal
- Creatinine < 1.5 x institutional upper limit of normal OR creatinine clearance >= 60 mL/min for patients with creatinine levels above 1.5 x institutional upper limit of normal
- Pregnant women will be excluded from this trial; nursing women are also excluded; women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) for the duration of study participation, and for 3 months after completion of study; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
- Patients should not be receiving any other investigational agents
Exclusion Criteria:
- Patients with clinically significant illnesses which would compromise participation in the study, including, but not limited to: active or uncontrolled infection, immune deficiencies or confirmed diagnosis of human immunodeficiency virus (HIV) infection, active Hepatitis B, active Hepatitis C, or uncontrolled diabetes, uncontrolled hypertension, symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction within the past 6 months, uncontrolled cardiac arrhythmia; or psychiatric illness/social situations that would limit compliance with study requirements
- Patients with additional (other than AML/MDS) currently active primary malignancy other than curatively treated carcinoma in situ (CIS) of the cervix, or basal or squamous cell carcinoma of the skin; patients are not considered to have a "currently active" malignancy if they have completed therapy for a prior malignancy and disease free from prior malignancies for > 2 years
- Patients with active central nervous system (CNS) disease; these patients are excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
- Active infections, including opportunistic following allo, MUD, or auto transplant (including but not limited to cytomegalovirus [CMV], fungal infection etc)
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (enzyme inhibitor therapy)
Patients receive FdCyd IV over 3 hours and THU IV over 3 hours on days 1-10.
Courses repeat every 21days in the absence of disease progression or unacceptable toxicity.
|
Correlative studies
Correlative studies
Other Names:
Correlative studies
Given IV
Other Names:
Given IV
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
MTD and dose-limiting toxicity (DLT) of the new 10-day schedule of FdCyd/THU
Time Frame: 10 days
|
Toxicities will be summarized by Common Terminology Criteria for Adverse Events (CTCAE) grade and attribution using the version current at the initiation of the protocol.
|
10 days
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Overall survival
Time Frame: 3 years
|
3 years
|
Toxicities of the FdCyd/THU treatment
Time Frame: 3 years
|
3 years
|
Time to progression
Time Frame: 3 years
|
3 years
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Robert Chen, MD, City of Hope Medical Center
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
December 1, 2009
Primary Completion (Actual)
October 1, 2013
Study Completion (Actual)
October 1, 2013
Study Registration Dates
First Submitted
December 29, 2009
First Submitted That Met QC Criteria
December 29, 2009
First Posted (Estimate)
December 31, 2009
Study Record Updates
Last Update Posted (Estimate)
June 8, 2015
Last Update Submitted That Met QC Criteria
June 3, 2015
Last Verified
June 1, 2015
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Disease
- Bone Marrow Diseases
- Hematologic Diseases
- Neoplastic Processes
- Precancerous Conditions
- Syndrome
- Myelodysplastic Syndromes
- Leukemia
- Leukemia, Myeloid
- Leukemia, Myeloid, Acute
- Neoplasm Metastasis
- Preleukemia
- Molecular Mechanisms of Pharmacological Action
- Antimetabolites
- Tetrahydrouridine
Other Study ID Numbers
- 09045
- NCI-2009-01661
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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