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

NCT ID: NCT02121418

Last Updated: 2018-04-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-06-30
• Study Completion Date: 2018-02-14

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.

Conditions

Chronic Myelomonocytic Leukemia-2; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Untreated Adult Acute Myeloid Leukemia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Cytarabine

Intervention Type: DRUG

Given IV

Decitabine

Intervention Type: DRUG

Given IV

Laboratory Biomarker Analysis

Intervention Type: OTHER

Correlative studies

Interventions

Cytarabine

Given IV

Intervention Type: DRUG

Decitabine

Given IV

Intervention Type: DRUG

Laboratory Biomarker Analysis

Correlative studies

Intervention Type: OTHER

Other Intervention 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; 5-Aza-2'-deoxycytidine; Dacogen; Decitabine for Injection; Deoxyazacytidine; Dezocitidine

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

• Minimum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

University of Washington

OTHER

Sponsor Role: lead

Responsible Party

Pamela S Becker

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Pamela Becker

Role: PRINCIPAL_INVESTIGATOR

Fred Hutch/University of Washington Cancer Consortium

Locations

Bozeman Deaconess Hospital

Bozeman, Montana, United States

Kadlec Clinic Hematology and Oncology

Kennewick, Washington, United States

EvergreenHealth Medical Center

Kirkland, Washington, United States

Skagit Valley Hospital

Mount Vernon, Washington, United States

Olympic Medical Center

Port Angeles, Washington, United States

Group Health Cooperative

Redmond, Washington, United States

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, United States

Multicare Health System

Tacoma, Washington, United States

Wenatchee Valley Hospital and Clinics

Wenatchee, Washington, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

NCI-2014-00769

Identifier Type: REGISTRY

Identifier Source: secondary_id

9019

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA015704

Identifier Type: NIH

Identifier Source: secondary_id

View Link

9019

Identifier Type: -

Identifier Source: org_study_id