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

Leukemia Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00534430
• Other study ID #: 99041
• Secondary ID: P30CA033572CHNMC
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: February 29, 2000
• Est. completion date: December 30, 2024

Study information

• Verified date: February 2024
• Source: City of Hope Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 30
• Est. completion date: December 30, 2024
• Est. primary completion date: April 12, 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Myelodysplastic Syndromes
• Preleukemia
• Syndrome

Intervention

Drug:
• busulfan

• cyclosporine

• etoposide

• mycophenolate mofetil

Procedure:
• allogeneic bone marrow transplantation

• allogeneic hematopoietic stem cell transplantation

• peripheral blood stem cell transplantation

Radiation:
• total-body irradiation

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
City of Hope Medical Center	National Cancer Institute (NCI)

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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%.	Date of Transplant to Five Years post-Transplant
Primary	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%.	Date of transplant to five years post-transplant
Primary	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%.	Date of Transplant to Five Years post-Transplant
Primary	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%.	Date of Transplant to Five Years post-Transplant. Estimate is at Five Years post-Transplant.