Controlled Study of Post-transplant Azacitidine for Prevention of Acute Myelogenous Leukemia and Myelodysplastic Syndrome Relapse (VZ-AML-PI-0129)

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00887068
• Collaborator: Celgene (Industry)
• Enrollment: 187
• Location: 1
• Arms: 2
• Actual Duration (Months): 112
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

The goal of this clinical research study is to learn if Vidaza (azacitidine) will help to control the disease in patients with AML, CMML, or MDS after an allogeneic (donor) stem cell transplant. The safety of this drug will also be studied.

Condition or Disease	Intervention/Treatment	Phase
Leukemia; AML; MDS	Drug: Azacitidine	Phase 3

Detailed Description

The Study Drug:

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

Study Groups:

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

• If you are in Group 1, you will receive azacitidine.

• If you are in Group 2, you will not receive azacitidine.

Study Drug Administration:

If you are in Group 1, you will receive azacitidine through a needle under your skin on Days 1-5 of each cycle.

Each cycle is 28 days long.

Your dose of azacitidine may be lowered or stopped if certain side effects develop.

Study Visits:

About 2 or 3 days before each cycle and, if your doctor thinks it is needed, on Day 3 of each cycle and 1 time during Weeks 2 and 3 of each cycle, blood (about 4 teaspoons each time) will be drawn for routine tests.

At 3, 6, and 12 months after the stem cell transplant:

• You will have a complete medical history and physical exam.

• Blood (about 4 teaspoons each time) will be drawn for routine tests.

• You will have a bone marrow aspiration to check the status of the disease.

You may come back for study visits more often if the doctor thinks it is needed.

While on study, you will need to stay in Houston for about 3 months after the transplant (this is standard after stem cell transplants).

Length of Study:

You will be on study treatment for up to 1 year (up to 12 cycles of azacitidine). You will be taken off study early if you experience intolerable side effects or the disease gets worse.

End-of-Treatment Visit:

After you complete the planned treatment with azacitidine, you will have an end-of-treatment visit:

• You will have a complete medical history and physical exam.

• Blood (about 4 teaspoons) will be drawn for routine tests.

• You will have a bone marrow aspiration to check the status of the disease.

This is an investigational study. Azacitidine is FDA approved and is commercially available for the treatment of myelodysplastic syndrome.

Up to 246 patients will take part in this study. All will be enrolled at MD Anderson.

Study Design

• Study Type: Interventional
• Actual Enrollment: 187 participants
• Allocation: Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Randomized Controlled Study of Post-transplant Azacitidine for Prevention of Acute Myelogenous Leukemia and Myelodysplastic Syndrome Relapse (VZ-AML-PI-0129)
• Actual Study Start Date: Apr 21, 2009
• Actual Primary Completion Date: Aug 20, 2018
• Actual Study Completion Date: Aug 20, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Azacitidine Azacitidine 32 mg/m^2 given through a needle under the skin for five consecutive days of each 28 day cycle and the maximum treatment will be 12 cycles.	Drug: Azacitidine; 32 mg/m^2 given through a needle under the skin for five consecutive days of each 28 day cycle and the maximum treatment will be 12 cycles.; Other Names: 5-Azacitidine 5-aza Vidaza 5-AZC AZA-CR Ladakamycin NSC-102816
No Intervention: No Azacitidine Standard treatment post allogeneic transplant is supportive care only.

Outcome Measures

Primary Outcome Measures

1. Relapse-free Survival (RFS) [3 years]

   The time that a participant survives without relapse of the disease.

Secondary Outcome Measures

1. Overall Survival (OS) [3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Patients with a diagnosis of AML (World Health Organization classification: >=20% blasts in the bone marrow and / or peripheral blood) or MDS (International Prognostic Scoring System intermediate-1 or higher) that at the time of allogeneic transplantation were in: - Induction Failure, relapsed disease or second or greater remission; patients in first complete remission that required more than 1 cycle of treatment to achieve the remission, or that have AML evolving from MDS, or that had the following abnormalities: FLT3 mutation, deletion of chromosome 5 or 7, MLL gene rearrangement, or more than or equal to 3 cytogenetics abnormalities. Patients with de novo or therapy-related MDS, CMML, or AML are also eligible, regardless of cytogenetics or molecular rearrangements.

2. Biphenotypic Leukemia that at the time of allogeneic transplantation was in induction failure, relapsed disease, first, second or greater remission.

3. Patients must be in complete remission post transplant.

4. Patient may be enrolled 40 to 100 days after transplant.

5. Age 18 to 75 years old.

6. Serum creatinine < 1.8 mg/dL or creatinine clearance greater or equal than 40 cc/min as defined by the Cockcroft-Gault Equation*. a. Males(mL/min):(140-age)IBW(kg) / 72(serum creatinine(mg/dl)) b. Females(mL/min):0.85*(140-age)IBW(kg) / 72(serum creatinine(mg/dl)).

7. Serum direct bilirubin < 1.5 mg/dL (unless Gilbert's syndrome).

8. SGPT </= 200 IU/ml unless related to patient's malignancy.

9. Be able to understand and sign informed consent.

Exclusion Criteria:

1. Active uncontrolled infection.

2. Presence of uncontrolled graft-versus-host disease.

3. Patients that underwent allogeneic transplantation as a treatment of graft failure.

4. Pregnancy or breast-feeding (women of childbearing potential, any female who has experienced menarche and who has not undergone surgical sterilization or is not post-menopausal with a positive serum pregnancy test.

5. Known or suspected hypersensitivity to azacitidine or mannitol.

6. Patients with advanced malignant hepatic tumors.

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
• Celgene

Investigators

• Principal Investigator: Richard E. Champlin, MD, BS, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Nov 10, 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: NCT00887068
• Other Study ID Numbers: 2008-0503; NCI-2012-01259
• First Posted: Apr 23, 2009
• Last Update Posted: Jan 14, 2020
• Last Verified: Jan 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; Acute myelogenous leukemia; AML; Myelodysplastic syndrome; MDS; Remission; Allogeneic stem cell transplant; Allotx; Azacitidine; 5-Azacitidine; 5-aza; Vidaza; 5-AZC; AZA-CR; Ladakamycin; NSC-102816
• Additional relevant MeSH terms: Leukemia; Preleukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Myelodysplastic Syndromes; Azacitidine

Study Results

Participant Flow

Recruitment Details	Recruitment was from September 2009 to April 2017 for high risk subjects with acute myelogenous leukemia (AML) and myelodysplastic (MDS) patients who have undergone an allogeneic transplant.
Pre-assignment Detail	Patients were randomized to receive azacitidine (AZA) or standard of care 40 to 100 days after allo SCT.

Arm/Group Title	AZA Group	Standard of Care Group
Arm/Group Description	Subjects randomized to the AZA treatment will receive 32 mg/m2 for 5 consecutive days of each 28 day cycle and the maximum treatment will be 12 cycles. Each cycle will consist of approximately 28 days, allowing the possibility that treatment within a cycle may be delayed for up to 4 weeks due to organ toxicity or hematologic toxicity.	Best standard of care (ie, no maintenance)
Period Title: Overall Study
STARTED	93	94
COMPLETED	87	94
NOT COMPLETED	6	0

Baseline Characteristics

Arm/Group Title	AZA Group	Standard of Care Group	Total
Arm/Group Description	Subjects randomized to the AZA treatment will receive 32 mg/m2 for 5 consecutive days of each 28 day cycle and the maximum treatment will be 12 cycles. Each cycle will consist of approximately 28 days, allowing the possibility that treatment within a cycle may be delayed for up to 4 weeks due to organ toxicity or hematologic toxicity.	Best standard of care (ie, no maintenance)	Total of all reporting groups
Overall Participants	87	94	181
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	71 81.6%	73 77.7%	144 79.6%
>=65 years	16 18.4%	21 22.3%	37 20.4%
Sex: Female, Male (Count of Participants)
Female	36 41.4%	37 39.4%	73 40.3%
Male	51 58.6%	57 60.6%	108 59.7%
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 2.3%	0 0%	2 1.1%
White	79 90.8%	92 97.9%	171 94.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	6 6.9%	2 2.1%	8 4.4%
Region of Enrollment (participants) [Number]
United States	87 100%	94 100%	181 100%
Disease Strata (Count of Participants)
AML	67 77%	67 71.3%	134 74%
MDS	26 29.9%	26 27.7%	52 28.7%
Biphenotypic Leukemia	0 0%	1 1.1%	1 0.6%

Outcome Measures

1. Primary Outcome

Title	Relapse-free Survival (RFS)
Description	The time that a participant survives without relapse of the disease.
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZA Group	Standard of Care Group
Arm/Group Description	Subjects randomized to the AZA treatment will receive 32 mg/m2 for 5 consecutive days of each 28 day cycle and the maximum treatment will be 12 cycles. Each cycle will consist of approximately 28 days, allowing the possibility that treatment within a cycle may be delayed for up to 4 weeks due to organ toxicity or hematologic toxicity.	Best standard of care (ie, no maintenance)
Measure Participants	87	94
Median (Standard Deviation) [years]	2.1 (.43)	1.3 (.43)

2. Secondary Outcome

Title	Overall Survival (OS)
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	AZA Group	Standard of Care Group
Arm/Group Description	Subjects randomized to the AZA treatment will receive 32 mg/m2 for 5 consecutive days of each 28 day cycle and the maximum treatment will be 12 cycles. Each cycle will consist of approximately 28 days, allowing the possibility that treatment within a cycle may be delayed for up to 4 weeks due to organ toxicity or hematologic toxicity.	Best standard of care (ie, no maintenance)
Measure Participants	87	94
Median (Standard Deviation) [years]	2.5 (.85)	2.6 (.85)

Adverse Events

Time Frame	From time of enrollment dependent on randomization would be one month from last day of study drug or one year if in standard of care group.
Arm/Group Title	AZA Group		Standard of Care Group
Arm/Group Description	Subjects randomized to the AZA treatment will receive 32 mg/m2 for 5 consecutive days of each 28 day cycle and the maximum treatment will be 12 cycles. Each cycle will consist of approximately 28 days, allowing the possibility that treatment within a cycle may be delayed for up to 4 weeks due to organ toxicity or hematologic toxicity.		Best standard of care (ie, no maintenance)
All Cause Mortality
	AZA Group		Standard of Care Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/87 (0%)		1/94 (1.1%)
Serious Adverse Events
	AZA Group		Standard of Care Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/87 (0%)		0/94 (0%)
Other (Not Including Serious) Adverse Events
	AZA Group		Standard of Care Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	29/87 (33.3%)		19/94 (20.2%)
Blood and lymphatic system disorders
Thrombocytopenia	29/87 (33.3%)		1/94 (1.1%)
Poor Graft function	29/87 (33.3%)		2/94 (2.1%)
Gastrointestinal disorders
Gastrointestetinal	0/87 (0%)		12/94 (12.8%)
Hepatobiliary disorders
Hepatic	8/87 (9.2%)		5/94 (5.3%)
Infections and infestations
Infection	0/87 (0%)		19/94 (20.2%)
Respiratory, thoracic and mediastinal disorders
Pulmonary	4/87 (4.6%)		6/94 (6.4%)
Skin and subcutaneous tissue disorders
Skin	2/87 (2.3%)		5/94 (5.3%)

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.