Clinical trial NCT00534430: Busulfan, Etoposide, and Total-Body Irradiation in Treating Patients Undergoing Donor Stem Cell or Bone Marrow Transplant for Advanced Hematologic Cancer
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Leukemia
Myelodysplastic Syndromes
Keywords: adult acute myeloid leukemia with 11q23 (MLL) abnormalities
adult acute myeloid leukemia with inv(16)(p13;q22)
adult acute myeloid leukemia with t(15;17)(q22;q12)
adult acute myeloid leukemia with t(16;16)(p13;q22)
adult acute myeloid leukemia with t(8;21)(q22;q22)
recurrent adult acute myeloid leukemia
adult acute myeloid leukemia in remission
recurrent childhood acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
recurrent childhood acute lymphoblastic leukemia
blastic phase chronic myelogenous leukemia
refractory anemia with excess blasts in transformation
refractory anemia with excess blasts
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
Lead sponsor: City of Hope Medical Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2007-09-24
Enrollment: 30
Sex: ALL
Minimum age (years): 16
Maximum age (years): 50
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Overall Survival at 5 Years Post-Transplant.
timeFrame: Date of Transplant to Five Years post-Transplant
measure: Disease-free Survival at Five Years Post-transplant
timeFrame: Date of transplant to five years post-transplant
measure: Overall Survival Comparing Diagnosis Groups
timeFrame: Date of Transplant to Five Years post-Transplant
measure: Cumulative Incidence of Relapse With Transplant-related Death as the Competing Risk: Diagnosis Groups Are Compared.
timeFrame: Date of Transplant to Five Years post-Transplant. Estimate is at Five Years post-Transplant.
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: City of Hope Comprehensive Cancer Center
name: Anthony S. Stein, MD
role: STUDY_CHAIR
References: