Decitabine and Cytarabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia, High Risk Myelodysplastic Syndrome, or Myeloproliferative Neoplasm

Decitabine Plus Cytarabine for Induction of Remission in Newly Diagnosed Elderly Acute Myeloid Leukemia (AML) and Advanced Myelodysplastic Syndrome (MDS)

This clinical trial studies decitabine and cytarabine in treating older patients with newly diagnosed acute myeloid leukemia, myelodysplastic syndrome that is likely to come back or spread to other places in the body, or myeloproliferative neoplasm. Drugs used in chemotherapy, such as decitabine and cytarabine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving decitabine and cytarabine may work better than standard therapies in treating cancers of the bone marrow and blood cells, such as acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasm.

Study Overview

• Status: Completed
• Conditions: Untreated Adult Acute Myeloid Leukemia; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Chronic Myelomonocytic Leukemia-2
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Drug: Decitabine; Drug: Cytarabine

Detailed Description

PRIMARY OBJECTIVES:

I. Examine whether a combination of decitabine given for 10 days (days 1-10), rather than the usual 5 days, plus "standard dose cytarabine (ara-C) (100 mg/m^2 daily days 1-7) might improve 6-month survival probability from the historical 65% to 80% in patients age >= 60 with newly diagnosed acute myeloid leukemia (AML).

II. Test whether this combination might maintain complete response (CR) rate at our historic 45% in these patients.

III. Study factors that lead physicians to escalate or maintain ara-C doses in those patients who have had an "intermediate response" short of CR to the first 2 cycles of the combination.

IV. While maintaining awareness of confounding covariates, examine the effect of such dose escalation on CR rate.

OUTLINE:

Patients receive decitabine intravenously (IV) daily on days 1-10 and cytarabine IV once daily (QD) on days 1-7. Treatment repeats every 28-35 days for 2 courses in the absence of disease progression or unacceptable toxicity. After course 3, patients achieving remission will receive 1-2 more courses of therapy at the same dose. Patients in remission with significant side effects will receive decitabine and cytarabine at decreased doses. Patients not achieving remission will not receive any more treatment.

After completion of study treatment, patients are followed up for 6 months and then periodically.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Montana
    • Bozeman, Montana, United States, 59715
      • Bozeman Deaconess Hospital
  • Washington
    • Kennewick, Washington, United States, 99336
      • Kadlec Clinic Hematology and Oncology
    • Kirkland, Washington, United States, 98033
      • EvergreenHealth Medical Center
    • Mount Vernon, Washington, United States, 98274
      • Skagit Valley Hospital
    • Port Angeles, Washington, United States, 98362
      • Olympic Medical Center
    • Redmond, Washington, United States, 98052
      • Group Health Cooperative
    • Seattle, Washington, United States, 98109
      • Fred Hutch/University of Washington Cancer Consortium
    • Tacoma, Washington, United States, 98415
      • MultiCare Health System
    • Wenatchee, Washington, United States, 98801
      • Wenatchee Valley Hospital and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Newly-diagnosed AML by World Health Organization (WHO) criteria (>= 20% myeloid blasts by morphology in either blood or marrow)
• High-risk myelodysplastic syndrome (MDS) or myeloproliferative neoplasm (MPN) including chronic myelomonocytic leukemia 2 (CMML2) as defined by 10-19% myeloid blasts in either blood or marrow
• Patients may have received azacitidine, decitabine, or lenalidomide but no "cytotoxic therapy" such as ara-C or anthracyclines; data suggest that failure to respond to azacitidine reduces probability of response to 3+7; hence in the interest of having a relatively homogeneous population, while patients who have received and failed azacitidine or decitabine will be eligible for this study, they will be analyzed separately from patients who have not received these drugs
• Treatment related mortality (TRM) score < 22.9; patients with TRM scores > 13.1, in whom the risk of death within 28 days of beginning induction therapy has averaged 41%, will preferentially be placed on protocol 2642
• Provision of written informed consent
• Note, unlike pharmaceutical company sponsored protocols eligibility is not conditioned on bilirubin, creatinine, or absence of other malignancy within the past 2-3 years; the TRM score incorporates creatinine and thus a high creatinine can in principle be offset by favorable values for the other covariates in the TRM score; bilirubin was not a covariate in the TRM; furthermore, in the doses we are using, dose adjustment of decitabine or ara-C is not indicated in the presence of renal or hepatic abnormalities; our broad eligibility criteria may increase the likelihood that our results will be generalizable; the inability to reproduce results of early phase AML studies has been a problem in the past

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

EXPERIMENTAL: Treatment (decitabine, cytarabine); Patients receive decitabine IV daily on days 1-10 and cytarabine IV QD on days 1-7. Treatment repeats every 28-35 days for 2 courses in the absence of disease progression or unacceptable toxicity. After course 3, patients achieving remission will receive 1-2 more courses of therapy at the same dose. Patients in remission with significant side effects will receive decitabine and cytarabine at decreased doses. Patients not achieving remission will not receive any more treatment.

Other: Laboratory Biomarker Analysis; Correlative studies; Drug: Decitabine; Given IV; Other Names: 5-Aza-2'-deoxycytidine; Dacogen; Decitabine for Injection; Deoxyazacytidine; Dezocitidine; Drug: Cytarabine; Given IV; Other Names: .beta.-Cytosine arabinoside; 1-.beta.-D-Arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-.beta.-D-Arabinofuranosylcytosine; 1-Beta-D-arabinofuranosyl-4-amino-2(1H)pyrimidinone; 1-Beta-D-arabinofuranosylcytosine; 1.beta.-D-Arabinofuranosylcytosine; 2(1H)-Pyrimidinone, 4-Amino-1-beta-D-arabinofuranosyl-; 2(1H)-Pyrimidinone, 4-amino-1.beta.-D-arabinofuranosyl-; Alexan; Ara-C; ARA-cell; Arabine; Arabinofuranosylcytosine; Arabinosylcytosine; Aracytidine; Aracytin; Aracytine; Beta-Cytosine Arabinoside; CHX-3311; Cytarabinum; Cytarbel; Cytosar; Cytosar-U; Cytosine Arabinoside; Cytosine-.beta.-arabinoside; Cytosine-beta-arabinoside; Erpalfa; Starasid; Tarabine PFS; U 19920; U-19920; Udicil; WR-28453

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival of Patients Over Age 60 With Newly Diagnosed AML/High Risk MDS	Compared to historical data of a completed Southwestern Oncology Group (SWOG) trial of azacitidine and gemtuzumab ozogamicin.	At 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Response Rate	Rate of Complete Response or Complete Response with Incomplete Count Recovery	Up to 2 years

Collaborators and Investigators

• Sponsor: University of Washington
• Collaborators: National Cancer Institute (NCI)

Study record dates

Study Major Dates

• Study Start: June 1, 2014
• Primary Completion (ACTUAL): February 8, 2017
• Study Completion (ACTUAL): February 14, 2018

Study Registration Dates

• First Submitted: April 21, 2014
• First Submitted That Met QC Criteria: April 21, 2014
• First Posted (ESTIMATE): April 23, 2014

Study Record Updates

• Last Update Posted (ACTUAL): April 13, 2018
• Last Update Submitted That Met QC Criteria: April 11, 2018
• Last Verified: April 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic-Myeloproliferative Diseases; Neoplasms; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Myeloproliferative Disorders; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Decitabine; Cytarabine
• Other Study ID Numbers: 9019 (OTHER: Fred Hutch/University of Washington Cancer Consortium); P30CA015704 (U.S. NIH Grant/Contract); NCI-2014-00769 (REGISTRY: CTRP (Clinical Trial Reporting Program))