Azacitidine After Allo Blood And Marrow Transplantation (BMT) for Chronic Myelogenous Leukemia (CML)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00813124
Recruitment Status : Completed
First Posted : December 22, 2008
Last Update Posted : October 1, 2014
National Cancer Institute (NCI)
Celgene Corporation
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Brief Summary:
The goal of this clinical research study is to learn if Vidaza (azacitidine) when given to patients with CML after an donor stem cell transplant will increase the likelihood of achieving a complete remission of CML.

Condition or disease Intervention/treatment Phase
Stem Cell Transplantation Leukemia Drug: Fludarabine Drug: Busulfan Drug: Thymoglobulin Drug: Azacitidine Procedure: Stem Cell Transplant Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Azacitidine Maintenance Therapy After Allogeneic Stem Cell Transplantation for Chronic Myelogenous Leukemia (CML)
Study Start Date : December 2008
Actual Primary Completion Date : September 2014

Arm Intervention/treatment
Experimental: Azacytidine Maintenance after allotx
Busulfan + Fludarabine + ATG + Azacytidine after allogeneic stem cell transplantation (allotx)
Drug: Fludarabine
40 mg/m^2 by vein over 60 minutes on Day -5 through Day -2.
Other Name: Fludarabine Phosphate
Drug: Busulfan
Busulfan administered at the dose calculated to achieve an area under curve (AUC) of 4000 µMol-min + 12% based on the pharmacokinetic studies (days -5, -4, -3, and -2).
Other Names:
  • Busulfex
  • Myleran
Drug: Thymoglobulin
2.5 mg/kg by vein over about 4-6 hours on Day -3 through Day -1.
Other Names:
  • Antithymocyte globulin
  • ATG
Drug: Azacitidine
Start cycles of 32 mg/m^2 daily as an injection under the skin once a day over 5 days in a row, starting about 5 weeks after the transplant. This may be repeated once a month for up to 4 months after the transplant.
Other Names:
  • 5-Azacitidine
  • 5-Aza
  • 5-AZC
  • Ladakamycin
  • NSC-102816
  • Vidaza
Procedure: Stem Cell Transplant
Stem cell infusion on day 0 administered by vein after collected from donor.
Other Names:
  • allotx
  • allogeneic stem cell transplantation

Primary Outcome Measures :
  1. Complete Molecular Remission Rate [ Time Frame: 1 Month ]
    Molecular Remission defined as 2 negative consecutive quantitative PCR tests done with a sensitivity of at least 1 in 105 cells, done at least one month apart.

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Patients with age <= 75 years with CML in first chronic phase, which has failed to achieve a cytogenetic or molecular complete remission or has progressed after imatinib treatment. Criteria for failure are the international consensus criteria (Appendix H). Patients intolerant to tyrosine kinase inhibitor therapy are also eligible.
  2. Patients with age <= 75 with CML in accelerated phase or blast crisis that have <= 15% blasts in the blood and bone marrow at study entry.
  3. Donor: HLA-compatible related (HLA-A, -B, -DRB1 matched or with one-antigen mismatch) or HLA-compatible unrelated (HLA-A, -B, -C and -DRB1 matched or with one-antigen mismatch).
  4. Age 18 to 75 years.
  5. Zubrod performance status <= 2.
  6. Left ventricular ejection fraction => 40%.
  7. Pulmonary function test within the following parameters: forced expiratory volume at one second (FEV1), forced vital capacity (FVC) and diffusing capacity of lung for carbon monoxide (DLCO) => 50% of expected, corrected for hemoglobin.
  8. Serum creatinine < 1.5 mg/dL or creatinine clearance greater or equal than 40 cc/min.
  9. Serum direct bilirubin < 1.5 mg/dL (unless Gilbert's syndrome)
  10. Serum glutamate pyruvate transaminase (SGPT) <= 200 IU/L unless related to patient's malignancy.
  11. Patients treated with any tyrosine kinase inhibitor, interferon or any experimental therapy are eligible.
  12. Patients with age <75 years with CML in second or subsequent chronic phase.

Exclusion Criteria:

  1. Uncontrolled infection, not responding to appropriate antimicrobial agents after seven days of therapy.
  2. Pleural/pericardial effusion or ascites estimated to be >1L.
  3. HIV-positive.
  4. Breast feeding or pregnancy. Pregnancy means a positive beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
  5. Known or suspected hypersensitivity to azacitidine or mannitol.
  6. Patients with advanced malignant hepatic tumors.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00813124

United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Celgene Corporation
Principal Investigator: Richard E. Champlin, MD, BS M.D. Anderson Cancer Center

Additional Information:
Responsible Party: M.D. Anderson Cancer Center Identifier: NCT00813124     History of Changes
Other Study ID Numbers: 2008-0087
NCI-2012-02122 ( Registry Identifier: NCI CTRP )
First Posted: December 22, 2008    Key Record Dates
Last Update Posted: October 1, 2014
Last Verified: September 2014

Keywords provided by M.D. Anderson Cancer Center:
Chronic Myelogenous Leukemia
Donor stem cell transplant
Allogeneic stem cell transplantation
Stem cell transplant
Antithymocyte globulin
Fludarabine Phosphate
Azacitidine maintenance therapy
molecular remission
HLA compatible donor
Graft vs host disease

Additional relevant MeSH terms:
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Fludarabine phosphate
Antilymphocyte Serum
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Alkylating Agents
Antineoplastic Agents, Alkylating
Myeloablative Agonists