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

Primary Purpose

Chronic Myelomonocytic Leukemia-2, Myelodysplastic Syndrome, Myeloproliferative Neoplasm

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Cytarabine
Decitabine
Laboratory Biomarker Analysis
Sponsored by
University of Washington
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Myelomonocytic Leukemia-2

Eligibility Criteria

60 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Bozeman Deaconess Hospital
  • Kadlec Clinic Hematology and Oncology
  • EvergreenHealth Medical Center
  • Skagit Valley Hospital
  • Olympic Medical Center
  • Group Health Cooperative
  • Fred Hutch/University of Washington Cancer Consortium
  • Multicare Health System
  • Wenatchee Valley Hospital and Clinics

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment (decitabine, cytarabine)

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Response Rate
Rate of Complete Response or Complete Response with Incomplete Count Recovery

Full Information

First Posted
April 21, 2014
Last Updated
April 11, 2018
Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT02121418
Brief Title
Decitabine and Cytarabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia, High Risk Myelodysplastic Syndrome, or Myeloproliferative Neoplasm
Official Title
Decitabine Plus Cytarabine for Induction of Remission in Newly Diagnosed Elderly Acute Myeloid Leukemia (AML) and Advanced Myelodysplastic Syndrome (MDS)
Study Type
Interventional

2. Study Status

Record Verification Date
April 2018
Overall Recruitment Status
Completed
Study Start Date
June 2014 (undefined)
Primary Completion Date
February 8, 2017 (Actual)
Study Completion Date
February 14, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Washington
Collaborators
National Cancer Institute (NCI)

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Myelomonocytic Leukemia-2, Myelodysplastic Syndrome, Myeloproliferative Neoplasm, Untreated Adult Acute Myeloid Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment (decitabine, cytarabine)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
.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
Intervention Description
Given IV
Intervention Type
Drug
Intervention Name(s)
Decitabine
Other Intervention Name(s)
5-Aza-2'-deoxycytidine, Dacogen, Decitabine for Injection, Deoxyazacytidine, Dezocitidine
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Laboratory Biomarker Analysis
Intervention Description
Correlative studies
Primary Outcome Measure Information:
Title
Overall Survival of Patients Over Age 60 With Newly Diagnosed AML/High Risk MDS
Description
Compared to historical data of a completed Southwestern Oncology Group (SWOG) trial of azacitidine and gemtuzumab ozogamicin.
Time Frame
At 6 months
Secondary Outcome Measure Information:
Title
Response Rate
Description
Rate of Complete Response or Complete Response with Incomplete Count Recovery
Time Frame
Up to 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Pamela Becker
Organizational Affiliation
Fred Hutch/University of Washington Cancer Consortium
Official's Role
Principal Investigator
Facility Information:
Facility Name
Bozeman Deaconess Hospital
City
Bozeman
State/Province
Montana
ZIP/Postal Code
59715
Country
United States
Facility Name
Kadlec Clinic Hematology and Oncology
City
Kennewick
State/Province
Washington
ZIP/Postal Code
99336
Country
United States
Facility Name
EvergreenHealth Medical Center
City
Kirkland
State/Province
Washington
ZIP/Postal Code
98033
Country
United States
Facility Name
Skagit Valley Hospital
City
Mount Vernon
State/Province
Washington
ZIP/Postal Code
98274
Country
United States
Facility Name
Olympic Medical Center
City
Port Angeles
State/Province
Washington
ZIP/Postal Code
98362
Country
United States
Facility Name
Group Health Cooperative
City
Redmond
State/Province
Washington
ZIP/Postal Code
98052
Country
United States
Facility Name
Fred Hutch/University of Washington Cancer Consortium
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Multicare Health System
City
Tacoma
State/Province
Washington
ZIP/Postal Code
98415
Country
United States
Facility Name
Wenatchee Valley Hospital and Clinics
City
Wenatchee
State/Province
Washington
ZIP/Postal Code
98801
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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