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

February 14, 2024 updated by: City of Hope Medical Center

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

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 50 years (Child, Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Busulfan, FTBI and VP16
IV Busulfan + 12 cGy FTBI + VP16 prior to allogeneic Bone Marrow Transplant
Drug: etoposide
Procedure: allogeneic bone marrow transplantation
Procedure: allogeneic hematopoietic stem cell transplantation
Radiation: total-body irradiation
Drug: busulfan
Procedure: peripheral blood stem cell transplantation
Drug: cyclosporine
Drug: mycophenolate mofetil

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overall Survival at 5 Years Post-Transplant.
Time Frame: Date of Transplant to Five 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%.
Date of Transplant to Five Years post-Transplant
Disease-free Survival at Five Years Post-transplant
Time Frame: Date of transplant to 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%.
Date of transplant to five years post-transplant
Overall Survival Comparing Diagnosis Groups
Time Frame: Date of Transplant to Five 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%.
Date of Transplant to Five Years post-Transplant
Cumulative Incidence of Relapse With Transplant-related Death as the Competing Risk: Diagnosis Groups Are Compared.
Time Frame: Date of Transplant to Five Years post-Transplant. Estimate is at Five Years post-Transplant.
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%.
Date of Transplant to Five Years post-Transplant. Estimate is at Five Years post-Transplant.

Secondary Outcome Measures

Outcome Measure
Time Frame
Early and late toxicities
Time Frame: 30 days, 31-100 days, 101 to 365 days and yearly through 5 years post transplant
30 days, 31-100 days, 101 to 365 days and yearly through 5 years post transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

City of Hope Medical Center

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Anthony S. Stein, MD, City of Hope Comprehensive Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 29, 2000

Primary Completion (Actual)

April 12, 2010

Study Completion (Estimated)

December 30, 2024

Study Registration Dates

First Submitted

September 20, 2007

First Submitted That Met QC Criteria

September 20, 2007

First Posted (Estimated)

September 24, 2007

Study Record Updates

Last Update Posted (Actual)

February 20, 2024

Last Update Submitted That Met QC Criteria

February 14, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 99041
  • P30CA033572 (U.S. NIH Grant/Contract)
  • CHNMC-99041
  • CDR0000564777 (Registry Identifier: NCI PDQ)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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