5-Fluoro-2'-Deoxycytidine and Tetrahydrouridine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

NCT01041443 | Completed Phase 1 DMC

• 2 other identifiers: 09045NCI-2009-01661
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Adult Acute Myeloid Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

Outcome Measures

Primary Outcomes (1)

• MTD and dose-limiting toxicity (DLT) of the new 10-day schedule of FdCyd/THU

  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 Outcomes (3)

• Toxicities of the FdCyd/THU treatment

  3 years

• Time to progression

  3 years

• Overall survival

  3 years

Study Arms (1)

Treatment (enzyme inhibitor therapy)

EXPERIMENTAL

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.

Drug: 5-fluoro-2-deoxycytidine; Drug: tetrahydrouridine; Other: laboratory biomarker analysis; Genetic: reverse transcriptase-polymerase chain reaction; Genetic: DNA methylation analysis

Interventions

5-fluoro-2-deoxycytidine DRUG

Given IV

Also known as: FdCyd

Treatment (enzyme inhibitor therapy)

tetrahydrouridine DRUG

Given IV

Also known as: THU

Treatment (enzyme inhibitor therapy)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (enzyme inhibitor therapy)

reverse transcriptase-polymerase chain reaction GENETIC

Correlative studies

Also known as: RT-PCR

Treatment (enzyme inhibitor therapy)

DNA methylation analysis GENETIC

Correlative studies

Treatment (enzyme inhibitor therapy)

Eligibility Criteria

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

You may qualify if:

• 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%

You may not qualify if:

• 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)

Sponsors & Collaborators

• City of Hope Medical Center: lead

Study Sites (1)

City of Hope

Duarte, California, 91010, United States

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

5-fluoro-2'-deoxycytidine; Tetrahydrouridine; Reverse Transcriptase Polymerase Chain Reaction; DNA Methylation

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Uridine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Polymerase Chain Reaction; Nucleic Acid Amplification Techniques; Genetic Techniques; Investigative Techniques; Methylation; Alkylation; Biochemical Phenomena; Chemical Phenomena; Metabolism; Genetic Phenomena

Study Officials

• Robert Chen, MD

  City of Hope Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 29, 2009
• First Posted: December 31, 2009
• Study Start: December 1, 2009
• Primary Completion: October 1, 2013
• Study Completion: October 1, 2013
• Last Updated: June 8, 2015

Record last verified: 2015-06

Locations

US (1)