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

NCT ID: NCT00887068

Last Updated: 2020-01-14

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 187 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-04-21
• Study Completion Date: 2018-08-20

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.

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.

Conditions

Leukemia; AML; MDS

Study Design

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

Study Groups

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.

Group Type: EXPERIMENTAL

Azacitidine

Intervention Type: DRUG

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.

No Azacitidine

Standard treatment post allogeneic transplant is supportive care only.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

5-Azacitidine; 5-aza; Vidaza; 5-AZC; AZA-CR; Ladakamycin; NSC-102816

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Celgene

INDUSTRY

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Richard E. Champlin, MD, BS

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

Oran B, de Lima M, Garcia-Manero G, Thall PF, Lin R, Popat U, Alousi AM, Hosing C, Giralt S, Rondon G, Woodworth G, Champlin RE. A phase 3 randomized study of 5-azacitidine maintenance vs observation after transplant in high-risk AML and MDS patients. Blood Adv. 2020 Nov 10;4(21):5580-5588. doi: 10.1182/bloodadvances.2020002544.

Reference Type: DERIVED

PMID: 33170934 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

http://www.mdanderson.org

University of Texas MD Anderson Cancer Center Website

Other Identifiers

NCI-2012-01259

Identifier Type: REGISTRY

Identifier Source: secondary_id

2008-0503

Identifier Type: -

Identifier Source: org_study_id