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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
City of Hope Medical Center
ClinicalTrials.gov Identifier:
NCT00534430
First received: September 20, 2007
Last updated: December 16, 2013
Last verified: December 2013
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Masking: 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

Resource links provided by NLM:


Further study details as provided by City of Hope Medical Center:

Primary Outcome Measures:
  • Efficacy [ Designated as safety issue: No ]
  • Disease-free survival at 2 years and 5 years [ Designated as safety issue: No ]
  • 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 [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Early and late toxicities [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: January 2000
Estimated Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)
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

Ages Eligible for Study:   16 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00534430

Sponsors and Collaborators
City of Hope Medical Center
Investigators
Study Chair: Anthony S. Stein, MD Beckman Research Institute
  More Information

Additional Information:
No publications provided

Responsible Party: City of Hope Medical Center
ClinicalTrials.gov Identifier: NCT00534430     History of Changes
Other Study ID Numbers: 99041, P30CA033572, CHNMC-99041, CDR0000564777
Study First Received: September 20, 2007
Last Updated: December 16, 2013
Health Authority: United States: Federal Government

Keywords provided by City of Hope Medical Center:
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

Additional relevant MeSH terms:
Leukemia
Myelodysplastic Syndromes
Preleukemia
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Busulfan
Cyclosporins
Cyclosporine
Mycophenolate mofetil
Etoposide phosphate
Etoposide
Mycophenolic Acid
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Enzyme Inhibitors
Antifungal Agents
Anti-Infective Agents
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on July 20, 2014