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Busulfan, Etoposide, and Total-Body Irradiation in Treating Patients Undergoing Donor Stem Cell or Bone Marrow Transplant for Advanced Hematologic Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00534430
First Posted: September 24, 2007
Last Update Posted: February 1, 2017
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.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
City of Hope Medical Center
  Purpose

RATIONALE: Giving chemotherapy and total-body irradiation before a donor stem cell transplant or a donor bone marrow transplant helps stop the growth of cancer and abnormal cells and helps stop the patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells. Giving mycophenolate mofetil and cyclosporine before and after transplant may stop this from happening.

PURPOSE: This phase II trial is studying the side effects and best way to give busulfan together with etoposide and total-body irradiation and to see how well they work in treating patients who are undergoing a donor stem cell or bone marrow transplant for advanced hematologic cancer.


Condition Intervention Phase
Leukemia Myelodysplastic Syndromes Drug: busulfan Drug: cyclosporine Drug: etoposide Drug: mycophenolate mofetil Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Radiation: total-body irradiation Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase II Study of IV Busulfan Combined With 12 cGy of Fractionated Total Body Irradiation (FTBI) and Etoposide (VP-16) as a Preparative Regimen for Allogeneic Bone Marrow Transplantation for Patients With Advanced Hematological Malignancies

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Efficacy as determined by disease free survival [ Time Frame: 5 years post transplant ]
  • Disease-free survival at 2 years and 5 years [ Time Frame: 5 years post transplant ]
  • Prognostic factors for relapse, disease-free survival, and overall survival evaluated by cytogenetics, WBC at presentation, targeted busulfan dose, and number of courses of induction therapy to achieve remission [ Time Frame: 5 years post transplant ]

Secondary Outcome Measures:
  • Early and late toxicities [ Time Frame: 30 days, 31-100 days, 101 to 365 days and yearly through 5 years post transplant ]

Estimated Enrollment: 50
Study Start Date: January 2000
Estimated Study Completion Date: January 2018
Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Busulfan, FTBI and VP16
IV Busulfan + 12 cGy FTBI + VP16 prior to allogeneic Bone Marrow Transplant
Drug: busulfan Drug: cyclosporine Drug: etoposide Drug: mycophenolate mofetil Procedure: allogeneic bone marrow transplantation Procedure: allogeneic hematopoietic stem cell transplantation Procedure: peripheral blood stem cell transplantation Radiation: total-body irradiation

Detailed Description:

OBJECTIVES:

  • To determine the efficacy of a preparative regimen comprising dose targeted busulfan, etoposide, and fractionated total-body irradiation followed by allogeneic hematopoietic stem cell or bone marrow transplantation in patients with advanced hematologic malignancies.
  • To determine the efficacy of this regimen in patients with acute myeloid leukemia in first remission with unfavorable cytogenetics.
  • To evaluate the early and late toxicities of this regimen.

OUTLINE:

  • Preparative chemotherapy regimen: Patients receive busulfan IV over 2 hours once every 6 hours on days -14 to -8 for a total of 16 doses and etoposide IV on day -3.* NOTE: *Patients also receive oral or IV dilantin 1-3 times daily on days -18 to -5 for prophylaxis of grand mal seizures.
  • Fractionated total-body irradiation (FTBI): Patients undergo FTBI on days -7 to -4 for a total of 10 fractions.
  • Allogeneic transplantation: Patients undergo allogeneic peripheral blood stem cell transplantation or bone marrow transplantation on day 0.
  • Graft-versus-host disease (GVHD) prophylaxis: Patients receive cyclosporine IV or orally on days -1 to 50 followed by a taper to day 180 in the absence of GVHD. Patients also receive mycophenolate mofetil orally or IV over 2 hours twice daily on days 0-27, followed by a taper until day 56.

After completion of study treatment, patients are followed annually for 2 years.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   16 Years to 50 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of 1 of the following:

    • Acute myeloid leukemia (AML)

      • Failed remission induction therapy or in relapse beyond second remission
      • In first remission with poor risk cytogenetics (e.g., 11q abnormalities, -7, -5, complex abnormalities [i.e., > 3 abnormalities, 6;9 translocation and 3q abnormalities del (7q), del (5q), complex abnormalities ≥ abnormalities, 9q, 20q, 21q, 17q, t(9;21)])
    • Acute lymphoblastic leukemia (ALL)

      • Failed remission induction therapy or in relapse beyond second remission
    • Blastic phase chronic myelogenous leukemia
    • Refractory anemia with excess blasts
    • Refractory anemia with excess blasts in transformation
  • HLA -A, -B, -C, -DR identical sibling donor match available
  • No relapse after prior bone marrow transplantation

PATIENT CHARACTERISTICS:

  • Cardiac ejection fraction ≥ 50%
  • Serum creatinine ≤ 1.2 times upper limit of normal (ULN) or creatinine clearance > 80 mL/min
  • Bilirubin ≤ 1.5 times ULN
  • AST and ALT < 5 times ULN
  • FEV_1 ≥ 50% of predicted normal
  • DLCO ≥ 50% of predicted normal
  • No psychological or medical condition that would preclude allogeneic transplantation (in the opinion of the treating physician)
  • Not pregnant
  • Negative pregnancy test

PRIOR CONCURRENT THERAPY:

  • See Disease Characteristics
  • At least 28 days since prior induction or reinduction therapy
  • Prior etoposide and busulfan allowed
  • No prior radiation therapy that would exclude total-body irradiation
  Contacts and Locations
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 ClinicalTrials.gov identifier (NCT number): NCT00534430


Sponsors and Collaborators
City of Hope Medical Center
National Cancer Institute (NCI)
Investigators
Study Chair: Anthony S. Stein, MD City of Hope Comprehensive Cancer Center
  More Information

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00534430     History of Changes
Other Study ID Numbers: 99041
P30CA033572 ( U.S. NIH Grant/Contract )
CHNMC-99041
CDR0000564777 ( Registry Identifier: NCI PDQ )
First Submitted: September 20, 2007
First Posted: September 24, 2007
Last Update Posted: February 1, 2017
Last Verified: January 2017

Keywords provided by City of Hope Medical Center:
adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent adult acute myeloid leukemia
adult acute myeloid leukemia in remission
recurrent childhood acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
blastic phase chronic myelogenous leukemia
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes

Additional relevant MeSH terms:
Syndrome
Leukemia
Myelodysplastic Syndromes
Preleukemia
Disease
Pathologic Processes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Etoposide
Etoposide phosphate
Mycophenolic Acid
Busulfan
Cyclosporins
Cyclosporine
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents