Decitabine Versus Azacitidine in Myelodysplastic Syndrome Patients With Low and Intermediate-1 Risk

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT01720225
• Collaborator: (none)
• Enrollment: 113
• Location: 1
• Arms: 2
• Actual Duration (Months): 86
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to compare how two different drugs, decitabine and azacitidine, when given on a shorter than standard dosing schedule can help to control MDS. The safety of the drugs will also be studied.

Decitabine is designed to damage the DNA (the genetic material) of cells, which may cause cancer cells to die.

Azacitidine is designed to block certain proteins in cancer cells whose job is to stop the function of the tumor-fighting proteins. By blocking the "bad" proteins, the tumor-fighting genes may be able to work better. This could cause the cancer cells to die.

Condition or Disease	Intervention/Treatment	Phase
Leukemia	Drug: Decitabine; Drug: Azacitidine	Phase 2

Detailed Description

Study Groups:

If you are found to be eligible to take part in this study, you will be randomly assigned (as in the flip of a coin) to 1 of 2 groups:

• If you are in Group 1, you will receive decitabine by vein over about 1 hour.

• If you are in Group 2, you will receive azacitidine either as an injection under your skin or through a vein. If by vein, the infusion will take about an hour.

At first, there will be an equal chance of being assigned to either group. However, as the study goes on and more information becomes available, the chance of being assigned to the group that has shown the most effectiveness will increase. However, once you are already enrolled and assigned to a group, you will not be eligible to change groups.

Study Drug Administration:

Each cycle is 28 days.

You will receive the study drug on Days 1-3 of every cycle and you will receive at least 2 cycles of study drug.

Study Visits:

Every 7-14 days, blood (about 2 tablespoons) will be drawn for routine tests.

At the end of Cycle 2, you will have a bone marrow biopsy and/or aspirate to check the status of the disease. This will then be repeated every 2-4 cycles until any point that the disease appears to have responded to the study drug, then as often as the study doctor thinks is necessary. To collect a bone marrow biopsy/aspirate, an area of the hip bone is numbed with anesthetic, and a small amount of bone and/or bone marrow is withdrawn through a large needle.

After Cycle 3:

If the study doctor decides it is acceptable, you may be allowed to receive treatment from your local cancer doctor. However, you have to return to Houston at least every 3 months for your study visits.

The frequency of the visits will depend on what the doctor thinks is in your best interest.

Length of Study:

You may continue taking the study drug for as long as the doctor thinks it is in your best interest. You will no longer be able to take the study drug if the disease gets worse, if intolerable side effects occur, or if you are unable to follow study directions.

Follow-Up Visits:

One (1) time every 3 months after your last dose of study drug, you will return to the clinic for a bone marrow aspiration to check the status of the disease.

Other Information:

You may be given other drugs to help prevent side effects. The study staff will tell you about these drugs, how they will be given, and the possible risks.

This is an investigational study. Decitabine and Azacitidine are both FDA approved and commercially available for use in patients with MDS.

Up to 120 patients will take part in this study. All will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 113 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase II Randomized Study of Lower Doses of Decitabine (DAC; 20 mg/m2 IV Daily for 3 Days Every Month) Versus Azacitidine (AZA; 75 mg/m2 SC/IV Daily for 3 Days Every Month) in Myelodysplastic Syndrome (MDS) Patients With Low and Intermediate-1 Risk Disease
• Actual Study Start Date: Nov 6, 2012
• Actual Primary Completion Date: Jan 8, 2020
• Actual Study Completion Date: Jan 8, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Decitabine Patients randomized to receive Decitabine 20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days.	Drug: Decitabine; 20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days.; Other Names: DAC Dacogen
Experimental: Azacitidine Patients randomized to receive Azacitidine 75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days.	Drug: Azacitidine; 75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days.; Other Names: AZA 5-azacytidine 5-aza Vidaza 5-AZC AZA-CR Ladakamycin NSC-102816

Outcome Measures

Primary Outcome Measures

1. Participants With a Response [56 days]

   Overall Response = complete remission (CR) + partial remission (PR) + marrow CR (mCR) + hematologic improvement (HI). CR is normalization of peripheral blood and bone marrow with <5% bone marrow blasts, a peripheral blood granulocyte count > (1.0 x 10^9/L, and platelet count > 100 x 10^9/L). PR is same as CR except for the presence of 6-15% marrow blasts, or 50% reduction if <15% at start of treatment. Marrow CR is blasts </= 5% and decreased by >/=50% from baseline. HI is platelets increase by 50% and to above 30 x 10^9/L untransfused (if lower than that pre-therapy; or hemoglobin increase by 2 g/dl; or transfusion independent; or splenomegaly reduction by > 50%; or monocytosis reduction by > 50% if pretreatment > 5 X1 0^9/L.

Secondary Outcome Measures

1. Number of Participants Who Became Transfusion Independent [8 weeks]

   Participants who were transfusion dependent at baseline prior to starting therapy on the Decitabine or Azacitidine arm will be analyzed for transfusion independence. Transfusion independence defined as being transfusion-free for ≥8 consecutive weeks between the first dose and study treatment discontinuation.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Sign an Institutional Review Board (IRB)-approved informed consent document.

2. Age >/= than18 years

3. de novo or secondary International Prostate Symptom Score (IPSS) low- or intermediate-1 - risk MDS, including CMML

4. Eastern Cooperative Oncology Group (ECOG) performance status of </= 3 at study entry.

5. Organ function as defined: Serum creatinine </= 3 x Upper Limit of Normal (ULN), Total bilirubin </= 2 x ULN, Alanine transaminase (ALT) (SGPT) </= 2 x ULN

6. Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days and will also need to use contraceptives. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.

Exclusion Criteria:

1. Breast feeding females

2. Prior therapy with decitabine or azacitidine

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

Investigators

• Principal Investigator: Elias Jabbour, MD, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 13, 2015

More Information

Additional Information:

• University of Texas MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT01720225
• Other Study ID Numbers: 2012-0507; NCI-2012-02215
• First Posted: Nov 2, 2012
• Last Update Posted: Dec 24, 2020
• Last Verified: Dec 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by M.D. Anderson Cancer Center: Leukemia; Myelodysplastic syndromes; MDS; Low and Intermediate-1 Risk Disease; Decitabine; DAC; Dacogen; Azacitidine; AZA; 5-azacytidine; 5-aza; Vidaza; 5-AZC; AZA-CR; Ladakamycin; NSC-102816
• Additional relevant MeSH terms: Preleukemia; Myelodysplastic Syndromes; Azacitidine; Decitabine

Study Results

Participant Flow

Recruitment Details	Recruitment Period: November 2012 to February 2016

Arm/Group Title	Decitabine	Azacitidine
Arm/Group Description	Patients randomized to receive Decitabine 20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days. Decitabine: 20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days.	Patients randomized to receive Azacitidine 75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days. Azacitidine: 75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days.
Period Title: Overall Study
STARTED	73	40
COMPLETED	70	39
NOT COMPLETED	3	1

Baseline Characteristics

Arm/Group Title	Decitabine	Azacitidine	Total
Arm/Group Description	Patients randomized to receive Decitabine 20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days. Decitabine: 20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days.	Patients randomized to receive Azacitidine 75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days. Azacitidine: 75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days.	Total of all reporting groups
Overall Participants	73	40	113
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	26 35.6%	12 30%	38 33.6%
>=65 years	47 64.4%	28 70%	75 66.4%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	70	70	70
Sex: Female, Male (Count of Participants)
Female	24 32.9%	16 40%	40 35.4%
Male	49 67.1%	24 60%	73 64.6%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	2 2.7%	1 2.5%	3 2.7%
White	71 97.3%	39 97.5%	110 97.3%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	73 100%	40 100%	113 100%

Outcome Measures

1. Primary Outcome

Title	Participants With a Response
Description	Overall Response = complete remission (CR) + partial remission (PR) + marrow CR (mCR) + hematologic improvement (HI). CR is normalization of peripheral blood and bone marrow with <5% bone marrow blasts, a peripheral blood granulocyte count > (1.0 x 10^9/L, and platelet count > 100 x 10^9/L). PR is same as CR except for the presence of 6-15% marrow blasts, or 50% reduction if <15% at start of treatment. Marrow CR is blasts </= 5% and decreased by >/=50% from baseline. HI is platelets increase by 50% and to above 30 x 10^9/L untransfused (if lower than that pre-therapy; or hemoglobin increase by 2 g/dl; or transfusion independent; or splenomegaly reduction by > 50%; or monocytosis reduction by > 50% if pretreatment > 5 X1 0^9/L.
Time Frame	56 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Decitabine	Azacitidine
Arm/Group Description	Patients randomized to receive Decitabine 20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days. Decitabine: 20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days.	Patients randomized to receive Azacitidine 75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days. Azacitidine: 75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days.
Measure Participants	70	39
Count of Participants [Participants]	49 67.1%	19 47.5%

2. Secondary Outcome

Title	Number of Participants Who Became Transfusion Independent
Description	Participants who were transfusion dependent at baseline prior to starting therapy on the Decitabine or Azacitidine arm will be analyzed for transfusion independence. Transfusion independence defined as being transfusion-free for ≥8 consecutive weeks between the first dose and study treatment discontinuation.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

Participants analyzed for Transfusion Independence must have been transfusion dependent at baseline. Thirty-seven participants in the Decitabine arm and nineteen participants in the Azacitidine arm where transfusion dependent prior to treatment on this study.

Arm/Group Title	Decitabine	Azacitidine
Arm/Group Description	Patients randomized to receive Decitabine 20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days. Decitabine: 20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days.	Patients randomized to receive Azacitidine 75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days. Azacitidine: 75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days.
Measure Participants	37	19
Count of Participants [Participants]	12 16.4%	3 7.5%

Adverse Events

Time Frame	3 years, 3 months
Arm/Group Title	Decitabine		Azacitidine
Arm/Group Description	Patients randomized to receive Decitabine 20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days. Decitabine: 20 mg/m2 by vein daily for 3 days (days 1-3) every 28 days.		Patients randomized to receive Azacitidine 75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days. Azacitidine: 75 mg/m2 subcutaneously or by vein daily for 3 days (days 1-3) every 28 days.
All Cause Mortality
	Decitabine		Azacitidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	7/73 (9.6%)		2/40 (5%)
Serious Adverse Events
	Decitabine		Azacitidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/73 (43.8%)		14/40 (35%)
Blood and lymphatic system disorders
Neutropenic Fever	9/73 (12.3%)	17	2/40 (5%)	2
Cardiac disorders
Heart Failure	2/73 (2.7%)	3	0/40 (0%)	0
Myocardial Infarction	1/73 (1.4%)	1	0/40 (0%)	0
Pericarditis	1/73 (1.4%)	1	0/40 (0%)	0
Ear and labyrinth disorders
Otitis Externa	1/73 (1.4%)	1	0/40 (0%)	0
Gastrointestinal disorders
Ascites	1/73 (1.4%)	1	0/40 (0%)	0
Diverticulitis	0/73 (0%)	0	1/40 (2.5%)	1
Gastroenteritis	1/73 (1.4%)	1	0/40 (0%)	0
Gastrointestinal Bleed	1/73 (1.4%)	1	0/40 (0%)	0
Nausea	1/73 (1.4%)	1	0/40 (0%)	0
Rectal Hermorrhage	1/73 (1.4%)	1	0/40 (0%)	0
Sialadenitis	0/73 (0%)	0	1/40 (2.5%)	1
Small Intestine Obstruction	0/73 (0%)	0	1/40 (2.5%)	1
General disorders
Back Pain	1/73 (1.4%)	1	0/40 (0%)	0
Chest Pain	1/73 (1.4%)	1	1/40 (2.5%)	1
Edema Limbs	0/73 (0%)	0	1/40 (2.5%)	1
Fatigue	1/73 (1.4%)	1	0/40 (0%)	0
Fever	2/73 (2.7%)	3	0/40 (0%)	0
Headache	1/73 (1.4%)	1	0/40 (0%)	0
Pain	1/73 (1.4%)	1	0/40 (0%)	0
Pain Abdominal Abcess	1/73 (1.4%)	1	0/40 (0%)	0
Pain Right Extremity	0/73 (0%)	0	1/40 (2.5%)	1
Right Hip Pain	0/73 (0%)	0	1/40 (2.5%)	1
Infections and infestations
Appendicitis	1/73 (1.4%)	1	0/40 (0%)	0
Cellulitis	0/73 (0%)	0	1/40 (2.5%)	1
Ear Infection	1/73 (1.4%)	1	0/40 (0%)	0
Tooth Infection	1/73 (1.4%)	1	0/40 (0%)	0
Joint Infection	1/73 (1.4%)	1	0/40 (0%)	0
Leg Infection	1/73 (1.4%)	1	0/40 (0%)	0
Lung Infection	3/73 (4.1%)	3	0/40 (0%)	0
Pneumonia	6/73 (8.2%)	7	1/40 (2.5%)	4
Salmonella Bactremia	0/73 (0%)	0	1/40 (2.5%)	1
Sepsis	4/73 (5.5%)	4	0/40 (0%)	0
Submandibular Cellulitis	1/73 (1.4%)	1	1/40 (2.5%)	1
Urinary Tract Infection	2/73 (2.7%)	2	1/40 (2.5%)	1
Wound Infection	1/73 (1.4%)	1	0/40 (0%)	0
Injury, poisoning and procedural complications
Fall	0/73 (0%)	0	1/40 (2.5%)	1
Food Poisoning	0/73 (0%)	0	1/40 (2.5%)	1
Nervous system disorders
Altered Mental Status	0/73 (0%)	0	1/40 (2.5%)	1
Intracranial Hemorrhage	1/73 (1.4%)	1	0/40 (0%)	0
Syncopal episode	1/73 (1.4%)	1	0/40 (0%)	0
Renal and urinary disorders
Acute Kidney Injury	1/73 (1.4%)	1	0/40 (0%)	0
Renal Failure	1/73 (1.4%)	1	0/40 (0%)	0
Reproductive system and breast disorders
Vaginal Fistual	0/73 (0%)	0	1/40 (2.5%)	1
Respiratory, thoracic and mediastinal disorders
Acute Respiratory Distress Syndrome	1/73 (1.4%)	1	0/40 (0%)	0
Bronchopulmonary Hemorrhage	0/73 (0%)	0	1/40 (2.5%)	1
Hemoptysis	1/73 (1.4%)	1	0/40 (0%)	0
Left plerual effusion	0/73 (0%)	0	1/40 (2.5%)	1
Right atelectasis	1/73 (1.4%)	1	0/40 (0%)	0
Right Pleural Effusion	1/73 (1.4%)	1	0/40 (0%)	0
Respiratory Failure	3/73 (4.1%)	3	0/40 (0%)	0
Shortness of Breath	1/73 (1.4%)	1	0/40 (0%)	0
Skin and subcutaneous tissue disorders
Groin Abcess	1/73 (1.4%)	1	0/40 (0%)	0
Skin Ulceration	1/73 (1.4%)	1	0/40 (0%)	0
Surgical and medical procedures
Cholecystectomy	1/73 (1.4%)	1	0/40 (0%)	0
Vascular disorders
Hypertension	1/73 (1.4%)	1	0/40 (0%)	0
Other (Not Including Serious) Adverse Events
	Decitabine		Azacitidine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/73 (27.4%)		16/40 (40%)
Gastrointestinal disorders
Nausea	11/73 (15.1%)	11	6/40 (15%)	6
Constipation	3/73 (4.1%)	3	6/40 (15%)	6
Diarrhea	2/73 (2.7%)	2	3/40 (7.5%)	3
General disorders
Fatigue	6/73 (8.2%)	6	4/40 (10%)	4

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.