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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

Primary Purpose

Leukemia, Myelodysplastic Syndromes

Status
Active
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
busulfan
cyclosporine
etoposide
mycophenolate mofetil
allogeneic bone marrow transplantation
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
total-body irradiation
Sponsored by
City of Hope Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia focused on measuring 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

Eligibility Criteria

16 Years - 50 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

    Arms of the Study

    Arm 1

    Arm Type

    Experimental

    Arm Label

    Busulfan, FTBI and VP16

    Arm Description

    IV Busulfan + 12 cGy FTBI + VP16 prior to allogeneic Bone Marrow Transplant

    Outcomes

    Primary Outcome Measures

    Overall Survival at 5 Years Post-Transplant.
    Kaplan-Meier estimate of an event of death estimated at five years post-transplant. 95% confidence intervals were calculated from the logit transform of the Greenwood variance. The transformation was necessary to keep the estimate within the probability space of 0 to 100%.
    Disease-free Survival at Five Years Post-transplant
    Kaplan-Meier estimate of an event of relapse or death estimated at five years post-transplant. 95% confidence intervals were calculated from the logit transform of the Greenwood variance. The transformation was necessary to keep the estimate within the probability space of 0 to 100%.
    Overall Survival Comparing Diagnosis Groups
    Kaplan-Meier estimate of an event of death estimated at five years post-transplant. 95% confidence intervals were calculated from the logit transform of the Greenwood variance. The transformation was necessary to keep the estimate within the probability space of 0 to 100%.
    Cumulative Incidence of Relapse With Transplant-related Death as the Competing Risk: Diagnosis Groups Are Compared.
    Fine and Gray estimate of cumulative incidence of Relapse, with Death as the competing risk. Estimate is at five years post-transplant. Ninety-five percent confidence interval is by logit transformation of Greenwood variance to keep the interval within the probability space of 0% to 100%.

    Secondary Outcome Measures

    Full Information

    First Posted
    September 20, 2007
    Last Updated
    October 6, 2023
    Sponsor
    City of Hope Medical Center
    Collaborators
    National Cancer Institute (NCI)
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00534430
    Brief Title
    Busulfan, Etoposide, and Total-Body Irradiation in Treating Patients Undergoing Donor Stem Cell or Bone Marrow Transplant for Advanced Hematologic Cancer
    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
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Active, not recruiting
    Study Start Date
    February 29, 2000 (Actual)
    Primary Completion Date
    April 12, 2010 (Actual)
    Study Completion Date
    December 30, 2023 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    City of Hope Medical Center
    Collaborators
    National Cancer Institute (NCI)

    4. Oversight

    5. Study Description

    Brief Summary
    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.
    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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Leukemia, Myelodysplastic Syndromes
    Keywords
    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

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 2
    Interventional Study Model
    Single Group Assignment
    Masking
    None (Open Label)
    Allocation
    N/A
    Enrollment
    30 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Busulfan, FTBI and VP16
    Arm Type
    Experimental
    Arm Description
    IV Busulfan + 12 cGy FTBI + VP16 prior to allogeneic Bone Marrow Transplant
    Intervention Type
    Drug
    Intervention Name(s)
    busulfan
    Intervention Type
    Drug
    Intervention Name(s)
    cyclosporine
    Intervention Type
    Drug
    Intervention Name(s)
    etoposide
    Intervention Type
    Drug
    Intervention Name(s)
    mycophenolate mofetil
    Intervention Type
    Procedure
    Intervention Name(s)
    allogeneic bone marrow transplantation
    Intervention Type
    Procedure
    Intervention Name(s)
    allogeneic hematopoietic stem cell transplantation
    Intervention Type
    Procedure
    Intervention Name(s)
    peripheral blood stem cell transplantation
    Intervention Type
    Radiation
    Intervention Name(s)
    total-body irradiation
    Primary Outcome Measure Information:
    Title
    Overall Survival at 5 Years Post-Transplant.
    Description
    Kaplan-Meier estimate of an event of death estimated at five years post-transplant. 95% confidence intervals were calculated from the logit transform of the Greenwood variance. The transformation was necessary to keep the estimate within the probability space of 0 to 100%.
    Time Frame
    Date of Transplant to Five Years post-Transplant
    Title
    Disease-free Survival at Five Years Post-transplant
    Description
    Kaplan-Meier estimate of an event of relapse or death estimated at five years post-transplant. 95% confidence intervals were calculated from the logit transform of the Greenwood variance. The transformation was necessary to keep the estimate within the probability space of 0 to 100%.
    Time Frame
    Date of transplant to five years post-transplant
    Title
    Overall Survival Comparing Diagnosis Groups
    Description
    Kaplan-Meier estimate of an event of death estimated at five years post-transplant. 95% confidence intervals were calculated from the logit transform of the Greenwood variance. The transformation was necessary to keep the estimate within the probability space of 0 to 100%.
    Time Frame
    Date of Transplant to Five Years post-Transplant
    Title
    Cumulative Incidence of Relapse With Transplant-related Death as the Competing Risk: Diagnosis Groups Are Compared.
    Description
    Fine and Gray estimate of cumulative incidence of Relapse, with Death as the competing risk. Estimate is at five years post-transplant. Ninety-five percent confidence interval is by logit transformation of Greenwood variance to keep the interval within the probability space of 0% to 100%.
    Time Frame
    Date of Transplant to Five Years post-Transplant. Estimate is at Five Years post-Transplant.

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    16 Years
    Maximum Age & Unit of Time
    50 Years
    Accepts Healthy Volunteers
    No
    Eligibility 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
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Anthony S. Stein, MD
    Organizational Affiliation
    City of Hope Comprehensive Cancer Center
    Official's Role
    Study Chair

    12. IPD Sharing Statement

    Learn more about this trial

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

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