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

NCT ID: NCT00534430

Last Updated: 2025-06-03

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2000-02-29
• Study Completion Date: 2026-03-18

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.

Conditions

Leukemia; Myelodysplastic Syndromes

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Busulfan, FTBI and VP16

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

Group Type: EXPERIMENTAL

busulfan

Intervention Type: DRUG

cyclosporine

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

mycophenolate mofetil

Intervention Type: DRUG

allogeneic bone marrow transplantation

Intervention Type: PROCEDURE

allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

total-body irradiation

Intervention Type: RADIATION

Interventions

busulfan

Intervention Type: DRUG

cyclosporine

Intervention Type: DRUG

etoposide

Intervention Type: DRUG

mycophenolate mofetil

Intervention Type: DRUG

allogeneic bone marrow transplantation

Intervention Type: PROCEDURE

allogeneic hematopoietic stem cell transplantation

Intervention Type: PROCEDURE

peripheral blood stem cell transplantation

Intervention Type: PROCEDURE

total-body irradiation

Intervention Type: RADIATION

Eligibility Criteria

Inclusion 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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

City of Hope Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Anthony S. Stein, MD

Role: STUDY_CHAIR

City of Hope Comprehensive Cancer Center

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

P30CA033572

Identifier Type: NIH

Identifier Source: secondary_id

View Link

CHNMC-99041

Identifier Type: -

Identifier Source: secondary_id

CDR0000564777

Identifier Type: REGISTRY

Identifier Source: secondary_id

99041

Identifier Type: -

Identifier Source: org_study_id