Study of Three Different Schedules of Low-Dose Decitabine in Myelodysplastic Syndrome (MDS)

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00067808
• Collaborator: Eisai Inc. (Industry)
• Enrollment: 128
• Location: 1
• Arms: 3
• Duration (Months): 67
• Patients Per Site Per Month: 1.9

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if decitabine (given at 3 different doses) can help to control Myelodysplastic Syndrome (MDS). The safety of these 3 treatments will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia	Drug: Decitabine; Drug: Decitabine; Drug: Decitabine	Phase 2

Detailed Description

Treatment: Methylation is a change that occurs to Deoxyribonucleic acid (DNA) that has an effect on gene usage in human cells. Abnormal methylation is very common in leukemias. Decitabine is a new drug that blocks DNA methylation.

Before treatment starts, a physical exam, blood tests (between 4-6 tablespoons), and a bone marrow study will be done. To collect a bone marrow sample, an area of the hip or chest bone is numbed with anesthetic and a small amount of bone marrow is withdrawn through a large needle. Women able to have children must have a negative blood or urine pregnancy test.

When this study began, participants were randomly assigned (as in the toss of a coin) to one of 3 treatment groups. The assignment to one of the 3 schedules was adjusted according to how well patients respond to treatment. About 17 patients were assigned to each group for the first 50 patients.

Participants in the first group received decitabine intravenously (IV--through a needle in their vein) over one hour, once a day, for 10 days. Treatment was given every 4 to 8 weeks depending on how well their blood counts recovered. Participants in the second group received decitabine as an IV infusion over one hour, once a day, for 5 days. Treatment was given every 4 to 8 weeks. Participants who received decitabine by vein got the same total dose per course. Participants in the third group received decitabine by subcutaneous (SQ) injections (injections given under the skin) twice a day for 5 days. As in the first and second group, treatment was given every 4 to 8 weeks.

After 65 patients were enrolled on this study, it was decided that the 5-day IV schedule was the best of the 3 schedules. The study will now continue with all new patients receiving the 5 -day IV decitabine treatment. If you are now enrolling on the study, you will be placed in this treatment group, instead of being randomly assigned to a treatment group.

Participants who are already on study and who are receiving the 5-day SQ schedule or the 10-day IV schedule, will be given the option to change to the 5-day IV schedule at the start of their next course of study drug treatment, since this is considered the new "standard" schedule on this particular study.

If you choose to take part in this study and begin receiving the study treatment described above, your response to treatment will be checked after completing 8 weeks of therapy. If the response to treatment is good, treatment with decitabine will continue. Decitabine treatment may be continued for up to 24 courses, or as long as it is judged best to control the leukemia.

During this study, you will need to visit your doctor for a physical exam and vital signs. The frequency of doctor visits will vary depending on your physical condition, but will be required at least once a month.

Blood tests (about 2 teaspoons) will be done about every week during the first 6-8 weeks of treatment, then every 1 to 2 weeks for the length of the study. The blood samples will be used for routine lab tests. Periodic bone marrow samples will also be taken to check cells related to the disease before, during, and after completion of this study.

Patients will be taken off study if the disease gets worse or intolerable side effects occur.

This is an investigational study. Decitabine is not yet Food and Drug Administration (FDA) approved.Up to 133 participants will be treated in this study. All will be enrolled at M. D. Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 128 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Randomized Study of Three Different Schedules of Low-Dose Decitabine (5-AZA-2'-Deoxycytidine) in Myelodysplastic Syndrome (MDS)
• Study Start Date: Oct 1, 2003
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Decitabine 10 mg/m^2 IV 10 mg/m^2 intravenous (IV) over 1 hour daily for 10 days	Drug: Decitabine; 10 mg/m^2 by vein over 1 hour daily for 10 days; Other Names: Dacogen
Active Comparator: Decitabine 20 mg/m2 IV 20 mg/m2 IV over 1 hour daily for 5 days	Drug: Decitabine; 20 mg/m2 by vein (IV) over 1 hour daily x 5 days; Other Names: Dacogen
Active Comparator: Decitabine 20 mg/m2 SQ 20 mg/m2 subcutaneous (SQ) daily for 5 days	Drug: Decitabine; 20 mg/m2 subcutaneous (SQ) daily x 5 days; Other Names: Dacogen

Outcome Measures

Primary Outcome Measures

1. Participant Responses [Response to treatment after 8 weeks of therapy]

   Objective responses by International Working Group criteria: 'Complete Response' (CR) defined as Normalization of the peripheral blood and bone marrow with <5% bone marrow blasts, a peripheral blood granulocyte count > (1.0 x 109/ L, and a platelet count > 100 x 109/L); 'Other Response' including Partial Remission (PR) defined as above, except for the presence of 6-15% marrow blasts, or 50% reduction if <15% at start of treatment combined with participants who meet all criteria for CR except for platelet recovery to >100 x 109/L; and 'No Response'.

Eligibility Criteria

Criteria

• Ages Eligible for Study: N/A and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. MDS and 5% or more marrow blasts, or IPSS risk intermediate 1-2 or high risk; or chronic myelomonocytic leukemia

2. Performance status 0-2 (Eastern Cooperative Oncology Group (ECOG) scale); adequate hepatic (bilirubin < 2 mg/dl) and renal functions (creatinine <2mg/dl); New York Heart Association (NYHA) cardiac status III-IV excluded.

3. Signed informed consent

4. No prior intensive combination chemotherapy or high-dose ara-C (>/= 1g/m2 per dose). Prior biologic therapies, targeted therapies and single agent chemotherapy allowed.

5. Patients must have been off chemotherapy for 2 weeks prior to entering this study and recovered from the toxic effects of that therapy, unless there is evidence of rapidly progressive disease. Use of Hydroxyurea for patients with rapidly proliferative disease is allowed for the first two weeks on therapy.

Exclusion Criteria:

1. Nursing and pregnant females are excluded. Patients of childbearing potential should practice effective methods of contraception. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

2. Patients with active and uncontrolled infections

3. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Texas - MD Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• Eisai Inc.

Investigators

• Principal Investigator: Hagop M Kantarjian, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• M.D. Anderson Cancer Center's website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT00067808
• Other Study ID Numbers: ID03-0180
• First Posted: Aug 28, 2003
• Last Update Posted: Aug 7, 2012
• Last Verified: Aug 1, 2012

• Keywords provided by M.D. Anderson Cancer Center: Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; MDS; Decitabine; Dacogen; Methylation
• Additional relevant MeSH terms: Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Myelodysplastic Syndromes; Syndrome; Decitabine

Study Results

Participant Flow

Recruitment Details	Recruitment Period 6/4/03 - 5/18/09; all patients were registered at The University of Texas M.D. Anderson Cancer Center.
Pre-assignment Detail	Enrollment of 128 patients: 1 patient withdrew consent prior to treatment; 3 did not meet eligibility requirement for a total of 124 evaluable patients.

Arm/Group Title	Decitabine 10 mg/m2 IV	Decitabine 20 mg/m2 IV	Decitabine 20 mg/m2 SQ
Arm/Group Description	10 mg/m2 by vein (IV) over 1 hour daily for 10 days	20 mg/m2 IV over 1 hour daily for 5 days	20 mg/m2 subcutaneous (SQ) daily for 5 days
Period Title: Overall Study
STARTED	17	93	14
COMPLETED	17	93	14
NOT COMPLETED	0	0	0

Baseline Characteristics

Arm/Group Title	Decitabine 10 mg/m2 IV	Decitabine 20 mg/m2 IV	Decitabine 20 mg/m2 SQ	Total
Arm/Group Description	10 mg/m2 by vein (IV) over 1 hour daily for 10 days	20 mg/m2 IV over 1 hour daily for 5 days	20 mg/m2 subcutaneous (SQ) daily for 5 days	Total of all reporting groups
Overall Participants	17	93	14	124
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	7 41.2%	45 48.4%	7 50%	59 47.6%
>=65 years	10 58.8%	48 51.6%	7 50%	65 52.4%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	67	65	64	65
Sex: Female, Male (Count of Participants)
Female	3 17.6%	33 35.5%	4 28.6%	40 32.3%
Male	14 82.4%	60 64.5%	10 71.4%	84 67.7%
Region of Enrollment (participants) [Number]
United States	17 100%	93 100%	14 100%	124 100%

Outcome Measures

1. Primary Outcome

Title	Participant Responses
Description	Objective responses by International Working Group criteria: 'Complete Response' (CR) defined as Normalization of the peripheral blood and bone marrow with <5% bone marrow blasts, a peripheral blood granulocyte count > (1.0 x 109/ L, and a platelet count > 100 x 109/L); 'Other Response' including Partial Remission (PR) defined as above, except for the presence of 6-15% marrow blasts, or 50% reduction if <15% at start of treatment combined with participants who meet all criteria for CR except for platelet recovery to >100 x 109/L; and 'No Response'.
Time Frame	Response to treatment after 8 weeks of therapy

Outcome Measure Data

Analysis Population Description

As treated: 124 patients completed treatment.

Arm/Group Title	Decitabine 10 mg/m2 IV	Decitabine 20 mg/m2 IV	Decitabine 20 mg/m2 SQ
Arm/Group Description	10 mg/m2 by vein (IV) over 1 hour daily for 10 days	20 mg/m2 IV over 1 hour daily for 5 days	20 mg/m2 subcutaneous (SQ) daily for 5 days
Measure Participants	17	93	14
Complete Response	4 23.5%	47 50.5%	4 28.6%
Other Response	6 35.3%	21 22.6%	4 28.6%
No Response	7 41.2%	25 26.9%	6 42.9%

Adverse Events

Time Frame	6 Years
Arm/Group Title	Decitabine 10 mg/m2 IV		Decitabine 20 mg/m2 IV		Decitabine 20 mg/m2 SQ
Arm/Group Description	10 mg/m2 by vein (IV) over 1 hour daily for 10 days		20 mg/m2 IV over 1 hour daily for 5 days		20 mg/m2 subcutaneous (SQ) daily for 5 days
All Cause Mortality
	Decitabine 10 mg/m2 IV		Decitabine 20 mg/m2 IV		Decitabine 20 mg/m2 SQ
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Decitabine 10 mg/m2 IV		Decitabine 20 mg/m2 IV		Decitabine 20 mg/m2 SQ
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/17 (29.4%)		32/93 (34.4%)		7/14 (50%)
Blood and lymphatic system disorders
Thrombocytopenia	1/17 (5.9%)	1	0/93 (0%)	0	0/14 (0%)	0
Cardiac disorders
Cardiac arrythmia	0/17 (0%)	0	1/93 (1.1%)	1	0/14 (0%)	0
Cardiac Ischemia	1/17 (5.9%)	1	2/93 (2.2%)	2	0/14 (0%)	0
Cardipulmonary arrest	0/17 (0%)	0	0/93 (0%)	0	1/14 (7.1%)	1
Elevated cardiac triponin	0/17 (0%)	0	1/93 (1.1%)	1	1/14 (7.1%)	1
Hypotension	1/17 (5.9%)	1	1/93 (1.1%)	1	0/14 (0%)	0
Supraventricular arrhythmia	1/17 (5.9%)	1	0/93 (0%)	0	0/14 (0%)	0
Syncope	0/17 (0%)	0	0/93 (0%)	0	1/14 (7.1%)	1
Gastrointestinal disorders
Cholecystitis	0/17 (0%)	0	1/93 (1.1%)	1	0/14 (0%)	0
Diarrhea	0/17 (0%)	0	1/93 (1.1%)	1	0/14 (0%)	0
diverticulitis	1/17 (5.9%)	1	0/93 (0%)	0	0/14 (0%)	0
Hemorrhage	0/17 (0%)	0	1/93 (1.1%)	1	0/14 (0%)	0
Ileus	0/17 (0%)	0	0/93 (0%)	0	1/14 (7.1%)	1
Small bowel obstruction	0/17 (0%)	0	0/93 (0%)	0	1/14 (7.1%)	1
General disorders
Adrenal Insufficiency	0/17 (0%)	0	0/93 (0%)	0	1/14 (7.1%)	1
Allergic Reaction	0/17 (0%)	0	2/93 (2.2%)	2	0/14 (0%)	0
Death	0/17 (0%)	0	6/93 (6.5%)	6	1/14 (7.1%)	1
Encephalopathy	0/17 (0%)	0	1/93 (1.1%)	1	0/14 (0%)	0
Pain	4/17 (23.5%)	5	13/93 (14%)	17	3/14 (21.4%)	3
Prolonged myelosuppression	0/17 (0%)	0	0/93 (0%)	0	1/14 (7.1%)	1
Vertigo	1/17 (5.9%)	1	0/93 (0%)	0	0/14 (0%)	0
Infections and infestations
Febrile neutropenia	0/17 (0%)	0	1/93 (1.1%)	1	1/14 (7.1%)	1
Infection	2/17 (11.8%)	2	3/93 (3.2%)	3	0/14 (0%)	0
Pneumonia	2/17 (11.8%)	2	2/93 (2.2%)	2	0/14 (0%)	0
Musculoskeletal and connective tissue disorders
Knee effusion	0/17 (0%)	0	1/93 (1.1%)	1	0/14 (0%)	0
Nervous system disorders
Neuropathy	0/17 (0%)	0	0/93 (0%)	0	1/14 (7.1%)	1
Renal and urinary disorders
Renal failure	2/17 (11.8%)	2	1/93 (1.1%)	1	0/14 (0%)	0
Respiratory, thoracic and mediastinal disorders
Dyspnea	2/17 (11.8%)	2	1/93 (1.1%)	1	0/14 (0%)	0
Pleural effusion	0/17 (0%)	0	1/93 (1.1%)	1	0/14 (0%)	0
Other (Not Including Serious) Adverse Events
	Decitabine 10 mg/m2 IV		Decitabine 20 mg/m2 IV		Decitabine 20 mg/m2 SQ
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/17 (23.5%)		32/93 (34.4%)		8/14 (57.1%)
Gastrointestinal disorders
Anorexia	1/17 (5.9%)	1	4/93 (4.3%)	4	0/14 (0%)	0
Diarrhea	0/17 (0%)	0	1/93 (1.1%)	1	1/14 (7.1%)	1
Nausea	1/17 (5.9%)	1	12/93 (12.9%)	13	1/14 (7.1%)	1
Vomiting	0/17 (0%)	0	3/93 (3.2%)	3	0/14 (0%)	0
General disorders
Allergic reaction	0/17 (0%)	0	0/93 (0%)	0	1/14 (7.1%)	1
Fatigue	0/17 (0%)	0	5/93 (5.4%)	5	1/14 (7.1%)	1
Pain	0/17 (0%)	0	3/93 (3.2%)	3	1/14 (7.1%)	1
Hepatobiliary disorders
Elevated alanine aminotransferase	1/17 (5.9%)	1	9/93 (9.7%)	9	0/14 (0%)	0
Elevated aspartate aminotransferase	1/17 (5.9%)	1	7/93 (7.5%)	7	0/14 (0%)	0
Hyperbilirubinemia	1/17 (5.9%)	1	8/93 (8.6%)	8	1/14 (7.1%)	1
Infections and infestations
Mucositis	0/17 (0%)	0	1/93 (1.1%)	1	0/14 (0%)	0
Renal and urinary disorders
Elevated Creatinine	0/17 (0%)	0	1/93 (1.1%)	1	0/14 (0%)	0
Skin and subcutaneous tissue disorders
Alopecia	0/17 (0%)	0	1/93 (1.1%)	1	1/14 (7.1%)	1
Injection site reaction	1/17 (5.9%)	1	0/93 (0%)	0	1/14 (7.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.