Azacitidine After Allo Blood And Marrow Transplantation (BMT) for Chronic Myelogenous Leukemia (CML) - Full Text View

Sponsor:	M.D. Anderson Cancer Center
Collaborator:	National Cancer Institute (NCI)
Information provided by (Responsible Party):	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00813124

Purpose

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.

Objectives:

To determine if post transplant treatment with 5-azacytidine will increase the rate of complete molecular remission in patients with chronic myelogenous leukemia (CML) following allogeneic stem cell transplantation from an HLA compatible donor compared to historical controls.

To determine the rate of engraftment, chimerism, graft-vs-host disease, and survival.

Condition	Intervention	Phase
Stem Cell Transplantation Leukemia	Drug: Fludarabine Drug: Busulfan Drug: Thymoglobulin Drug: Azacitidine Procedure: Stem Cell Transplant	Phase II

Study Type:	Interventional
Study Design:	Endpoint Classification: Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Azacitidine Maintenance Therapy After Allogeneic Stem Cell Transplantation for Chronic Myelogenous Leukemia (CML)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Chronic Myeloid Leukemia Leukemia

Drug Information available for: Busulfan Fludarabine Fludarabine monophosphate Azacitidine

U.S. FDA Resources

Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:

Complete Molecular Remission Rate [ Time Frame: 1 Month ] [ Designated as safety issue: No ]
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.

Estimated Enrollment:	32
Study Start Date:	December 2008
Estimated Primary Completion Date:	December 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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 -6 through Day -3. Other Name: Fludarabine Phosphate Drug: Busulfan 130 mg/m^2 by vein over about 3 hours on Day -4 and Day -3. Other Names: Busulfex Myleran Drug: Thymoglobulin 1.5 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

Arms

Assigned Interventions

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 -6 through Day -3.

Other Name: Fludarabine Phosphate

Drug: Busulfan

130 mg/m^2 by vein over about 3 hours on Day -4 and Day -3.

Other Names:

Busulfex
Myleran

Drug: Thymoglobulin

1.5 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

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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.
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.
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).
Age 18 to 75 years.
Zubrod performance status <= 2.
Left ventricular ejection fraction => 40%.
Pulmonary function test within the following parameters: FEV1, FVC and DLCO => 50% of expected, corrected for hemoglobin.
Serum creatinine < 1.5 mg/dL or creatinine clearance greater or equal than 40 cc/min.
Serum direct bilirubin < 1.5 mg/dL (unless Gilbert's syndrome)
SGPT <= 200 IU/L unless related to patient's malignancy.
Patients treated with any tyrosine kinase inhibitor, interferon or any experimental therapy are eligible.
Patients with age <75 years with CML in second or subsequent chronic phase.

Exclusion Criteria:

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00813124

Contacts

Contact: Marcos de Lima, MD

713-792-8750

Locations

United States, Texas
UT MD Anderson Cancer Center	Recruiting
Houston, Texas, United States, 77030
Principal Investigator: Marcos de Lima, MD

Sponsors and Collaborators

M.D. Anderson Cancer Center

National Cancer Institute (NCI)

Investigators

Principal Investigator:

Marcos de Lima, MD

UT MD Anderson Cancer Center

More Information

Additional Information:

UT MD Anderson Cancer Center website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:	NCT00813124 History of Changes
Other Study ID Numbers:	2008-0087
Study First Received:	December 18, 2008
Last Updated:	December 30, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:

Chronic Myelogenous Leukemia
CML
Donor stem cell transplant
Allogeneic stem cell transplantation
Stem cell transplant
ATG
Antithymocyte globulin
Vidaza
Azacitidine
5-Azacitidine
5-Aza
5-AZC
Ladakamycin
NSC-102816
allotx

Busulfan
Busulfex
Myleran
Fludarabine
Fludarabine Phosphate
Tacrolimus
Methotrexate
Azacitidine maintenance therapy
molecular remission
HLA compatible donor
Engraftment
Chimerism
Graft vs host disease
GVHD

Additional relevant MeSH terms:

Leukemia
Leukemia, Myeloid
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Neoplasms by Histologic Type
Neoplasms
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Antilymphocyte Serum
Busulfan
Fludarabine monophosphate
Azacitidine
Vidarabine
Fludarabine
Immunosuppressive Agents

Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Antineoplastic Agents, Alkylating
Alkylating Agents
Myeloablative Agonists
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on February 09, 2012