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

Sponsor

City of Hope Medical Center (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT00534430

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Arm

274

Anticipated Duration (Months)

Study Details

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.

Condition or Disease	Intervention/Treatment	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

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 Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

N/A

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

Actual Study Start Date :

Feb 29, 2000

Anticipated Primary Completion Date :

Dec 30, 2022

Anticipated Study Completion Date :

Dec 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

Primary Outcome Measures

Efficacy as determined by disease free survival [5 years post transplant]
Disease-free survival at 2 years and 5 years [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 [5 years post transplant]

Secondary Outcome Measures

Early and late toxicities [30 days, 31-100 days, 101 to 365 days and yearly through 5 years post transplant]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years to 50 Years

Sexes Eligible for Study:

All

Accepts 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