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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Celgene Corporation
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00813124
First received: December 18, 2008
Last updated: March 10, 2014
Last verified: March 2014
  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.


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

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:


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: 57
Study Start Date: December 2008
Estimated Primary Completion Date: December 2015 (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 -5 through Day -2.
Other Name: Fludarabine Phosphate
Drug: Busulfan
Busulfan administered at the dose calculated to achieve an 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

  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:

  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: FEV1, FVC and 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. 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 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

Locations
United States, Texas
UT MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Celgene Corporation
Investigators
Principal Investigator: Richard E. Champlin, MD, BS UT MD Anderson Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00813124     History of Changes
Other Study ID Numbers: 2008-0087, NCI-2012-02122
Study First Received: December 18, 2008
Last Updated: March 10, 2014
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 phosphate
Azacitidine
Vidarabine
Fludarabine
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Immunosuppressive Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Enzyme Inhibitors
Alkylating Agents
Antineoplastic Agents, Alkylating
Myeloablative Agonists
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on August 28, 2014