Overview

This trial is active, not recruiting.

Conditions leukemia, myelodysplastic syndromes
Treatments busulfan, cyclosporine, etoposide, mycophenolate mofetil, allogeneic bone marrow transplantation, allogeneic hematopoietic stem cell transplantation, peripheral blood stem cell transplantation, total-body irradiation
Phase phase 2
Sponsor City of Hope Medical Center
Collaborator National Cancer Institute (NCI)
Start date January 2000
End date June 2016
Trial size 50 participants
Trial identifier NCT00534430, 99041, CDR0000564777, CHNMC-99041, P30CA033572

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
IV Busulfan + 12 cGy FTBI + VP16 prior to allogeneic Bone Marrow Transplant
busulfan
cyclosporine
etoposide
mycophenolate mofetil
allogeneic bone marrow transplantation
allogeneic hematopoietic stem cell transplantation
peripheral blood stem cell transplantation
total-body irradiation

Primary Outcomes

Measure
Efficacy as determined by disease free survival
time frame: 5 years post transplant
Disease-free survival at 2 years and 5 years
time frame: 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
time frame: 5 years post transplant

Secondary Outcomes

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

Eligibility Criteria

Male or female participants from 16 years up to 50 years old.

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

Additional Information

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
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.
Trial information was received from ClinicalTrials.gov and was last updated in January 2015.
Information provided to ClinicalTrials.gov by City of Hope Medical Center.