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

• Sponsor: University of Washington (Other)
• Overall Status: Completed
• CT.gov ID: NCT02121418
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 12
• Locations: 9
• Arm: 1
• Duration (Months): 44.5
• Patients Per Site: 1.3
• Patients Per Site Per Month: 0

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Myelomonocytic Leukemia-2; Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Untreated Adult Acute Myeloid Leukemia	Drug: Cytarabine; Drug: Decitabine; Other: Laboratory Biomarker Analysis	N/A

Detailed Description

PRIMARY OBJECTIVES:

1. 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).

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

3. 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.

4. 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 Design

• Study Type: Interventional
• Actual Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Decitabine Plus Cytarabine for Induction of Remission in Newly Diagnosed Elderly Acute Myeloid Leukemia (AML) and Advanced Myelodysplastic Syndrome (MDS)
• Study Start Date: Jun 1, 2014
• Actual Primary Completion Date: Feb 8, 2017
• Actual Study Completion Date: Feb 14, 2018

Arms and Interventions

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.

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 ; Drug: Decitabine; Given IV; Other Names: 5-Aza-2'-deoxycytidine Dacogen Decitabine for Injection Deoxyazacytidine Dezocitidine ; Other: Laboratory Biomarker Analysis; Correlative studies

Outcome Measures

Primary Outcome Measures

1. Overall Survival of Patients Over Age 60 With Newly Diagnosed AML/High Risk MDS [At 6 months]

   Compared to historical data of a completed Southwestern Oncology Group (SWOG) trial of azacitidine and gemtuzumab ozogamicin.

Secondary Outcome Measures

1. Response Rate [Up to 2 years]

   Rate of Complete Response or Complete Response with Incomplete Count Recovery

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Bozeman Deaconess Hospital	Bozeman	Montana	United States	59715
2	Kadlec Clinic Hematology and Oncology	Kennewick	Washington	United States	99336
3	EvergreenHealth Medical Center	Kirkland	Washington	United States	98033
4	Skagit Valley Hospital	Mount Vernon	Washington	United States	98274
5	Olympic Medical Center	Port Angeles	Washington	United States	98362
6	Group Health Cooperative	Redmond	Washington	United States	98052
7	Fred Hutch/University of Washington Cancer Consortium	Seattle	Washington	United States	98109
8	Multicare Health System	Tacoma	Washington	United States	98415
9	Wenatchee Valley Hospital and Clinics	Wenatchee	Washington	United States	98801

Sponsors and Collaborators

• University of Washington
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Pamela Becker, Fred Hutch/University of Washington Cancer Consortium

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Mar 22, 2017

More Information

Publications

None provided.

• Responsible Party: Pamela S Becker, Principal Investigator, University of Washington
• ClinicalTrials.gov Identifier: NCT02121418
• Other Study ID Numbers: 9019; NCI-2014-00769; 9019; P30CA015704
• First Posted: Apr 23, 2014
• Last Update Posted: Apr 13, 2018
• Last Verified: Apr 1, 2018

• Additional relevant MeSH terms: Leukemia; Neoplasms; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes; Myeloproliferative Disorders; Syndrome; Cytarabine; Decitabine

Study Results

Participant Flow

Arm/Group Title	Treatment (Decitabine, Cytarabine)
Arm/Group 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. 12 patients were consented and treated.
Period Title: Overall Study
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Decitabine, Cytarabine)
Arm/Group 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. 12 patients were consented and treated.
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	12 100%
Sex: Female, Male (Count of Participants)
Female	3 25%
Male	9 75%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 8.3%
Not Hispanic or Latino	9 75%
Unknown or Not Reported	2 16.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 8.3%
Asian	1 8.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	8 66.7%
More than one race	1 8.3%
Unknown or Not Reported	1 8.3%
Region of Enrollment (participants) [Number]
United States	12 100%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Decitabine, Cytarabine)
Arm/Group 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. 12 patients were consented and treated.
Measure Participants	12
Number [participants]	7 58.3%

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Decitabine, Cytarabine)
Arm/Group 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. 12 patients were consented and treated.
Measure Participants	12
Complete Respnose	4 33.3%
Complete Response with Incomplete Count Recovery	3 25%

Adverse Events

Time Frame	2 years
Adverse Event Reporting Description	Other [not including serious] adverse events were not addressed.
Arm/Group Title	Treatment (Decitabine, Cytarabine)
Arm/Group 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. 12 patients were consented and treated.
All Cause Mortality
	Treatment (Decitabine, Cytarabine)
	Affected / at Risk (%)	# Events
Total	9/12 (75%)
Serious Adverse Events
	Treatment (Decitabine, Cytarabine)
	Affected / at Risk (%)	# Events
Total	11/12 (91.7%)
Blood and lymphatic system disorders
Hypertension	1/12 (8.3%)	1
Cardiac disorders
Syncope	1/12 (8.3%)	1
Afibrillation	1/12 (8.3%)	1
Gastrointestinal disorders
Diarrhea	1/12 (8.3%)	1
Esophagogastric mucosal junction ulcer	1/12 (8.3%)	1
General disorders
Fatigue	1/12 (8.3%)	1
Hepatobiliary disorders
Bacterial Liver Abscess	1/12 (8.3%)	1
Infections and infestations
Febrile Neutropenia	4/12 (33.3%)	5
Pneumonia	6/12 (50%)	6
MRSA Bacteremia	1/12 (8.3%)	1
Staph Bacteremia	2/12 (16.7%)	2
Bacteremia	1/12 (8.3%)	1
C. Difficile Diarrhea	1/12 (8.3%)	1
Pyomyositis of B/L calf	1/12 (8.3%)	1
Clostridium Ramosum bacteremia	1/12 (8.3%)	1
Rothia Bacteremia	1/12 (8.3%)	1
Oral mucositis	1/12 (8.3%)	1
Diverticulitis	1/12 (8.3%)	1
Investigations
Hyponatremia	1/12 (8.3%)	1
Hypokalemia	1/12 (8.3%)	1
Hyperbilirubinemia	1/12 (8.3%)	1
Musculoskeletal and connective tissue disorders
Muscle Weakness	2/12 (16.7%)	2
Hypoxia	1/12 (8.3%)	1
Skin and subcutaneous tissue disorders
Right cheek cellulitis	1/12 (8.3%)	1
Rash	1/12 (8.3%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Decitabine, Cytarabine)
	Affected / at Risk (%)	# Events
Total	0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.