Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Busulfan Monotherapy as Conditioning for Autologous Hematopoietic Progenitor Cell Transplantation

This study has been terminated.
(Low accrual)
Sponsor:
Collaborator:
ESP Pharma
Information provided by (Responsible Party):
H. Lee Moffitt Cancer Center and Research Institute
ClinicalTrials.gov Identifier:
NCT00363467
First received: August 10, 2006
Last updated: August 24, 2011
Last verified: August 2011

August 10, 2006
August 24, 2011
May 2006
May 2009   (final data collection date for primary outcome measure)
100-day Non-relapse Mortality [ Time Frame: 100 days post transplant ] [ Designated as safety issue: Yes ]
100-day non-relapse mortality is the number of participants who died before day 100 posttransplant from causes other than relapsed disease
100-day non-relapse mortality
Complete list of historical versions of study NCT00363467 on ClinicalTrials.gov Archive Site
  • Successful Autologous Stem Cell Collection [ Time Frame: At time of stem cell collection ] [ Designated as safety issue: No ]
    Number of subjects who were able to collect at least 2 million CD34+ cells/kg
  • Severe Regimen-related Toxicity [ Time Frame: up to 100 days post translant ] [ Designated as safety issue: Yes ]
    Number of participants with severe regimen-related toxicity within 2 years posttransplant. Severe regimen-related toxicity was defined as CTC (version 3)grade 4.
  • 1 Year Event-free Survival [ Time Frame: 1 year post transplant ] [ Designated as safety issue: No ]
    Number of participants alive and without disease relapse at 1 year posttransplant
  • 1 Year Overall Survival [ Time Frame: 1 year post transplant ] [ Designated as safety issue: No ]
    Number of participants alive at 1 year posttransplant
  • Rate of successful autologous stem cell collection
  • Rate of severe regimen-related toxicity
  • Event-free survival measured from the time at which criteria are met for CR until the first date that recurrent or progressive disease is objectively documented, or death from any cause occurs
  • Overall survival measured from time of CR to the time of death
Not Provided
Not Provided
 
Busulfan Monotherapy as Conditioning for Autologous Hematopoietic Progenitor Cell Transplantation
A Pilot Study of Intravenous, Targeted-Dose Busulfan Monotherapy as Conditioning for Autologous Hematopoietic Progenitor Cell Transplantation in High-Risk AML

During the pre-transplantation phase (following completion of consolidation chemotherapy), patients will begin to receive G-CSF at 10 mcg/kg twice daily; leukapheresis will also be given until a target goal for recipient body weight is obtained, or up to a maximum of 5 days. Conditioning/Preparative therapy will follow PBSC collection for up to 30 days with Busulfan IV daily x 4 days; subsequent doses will be adjusted based on pharmacokinetic (plasma level)monitoring. Following 1 day of rest, stem cell reinfusion will begin with supportive care. During follow-up, patients will be monitored out to 730 days.

  1. Pre- Transplantation Phase -

    1. Twenty-four to 48 hours following completion of consolidation chemotherapy, patients will begin to receive G-CSF at 10 mcg/kg twice daily subcutaneously. Alternatively, patients may receive G-CSF alone (same dose) as mobilization therapy.
    2. Leukapheresis will begin day 4 of G-CSF administration and proceed according to institutional guidelines. Leukapheresis will continue until a target goal for recipient body weight is obtained, or up to a maximum of 5 days. A minimum recipient body weight is required to proceed to transplantation.
  2. Transplantation Phase

    a. Conditioning/Preparative therapy - up to 30 days following PBSC collection, patients will begin conditioning therapy with Busulfan IV daily x 4 days (transplantation days -5,-4,-3,-2). The day -5 and -4 dose will be 130mg/m2; subsequent doses will be adjusted based on pharmacokinetic monitoring.

    • Busulfan plasma level monitoring, collected around the first dose of busulfan b. Stem cell reinfusion - following 1 day of rest, previously collected autologous peripheral blood stem cells will be infused.
    • The administration of supportive measures (e.g. intravenous fluids, antihistamines) during stem cell reinfusion will be performed according to institutional guidelines.
  3. Supportive care

    1. Antibiotic prophylaxis- according to hospital/institutional guidelines, and at the discretion of the treating physician.
    2. Growth factor support
    3. Transfusion support
    4. Prophylaxis for busulfan-induced seizures
  4. During follow-up, patients will be seen at least weekly for the first month and there after periodically out to 730 days posttransplant. The following medical procedures will be done:

    • Medical history and physical exam (including concurrent meds, vital signs, performance status and weight)
    • Standard labs
    • Bone marrow aspirate and biopsy
Interventional
Not Provided
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Acute Myeloid Leukemia (AML)
  • Drug: G-CSF

    Mobilization Option 1:Twenty-four to 48 hours following completion of consolidation chemotherapy, patients will begin to receive G-CSF at 10 mcg/kg twice daily subcutaneously.

    Mobilization Option 2: If patients have recovered hematologically from consolidation chemotherapy, they may receive G-CSF at 10 mcg/kg twice daily subcutaneously.

    Other Name: filgrastim or NeupogenR
  • Drug: Leukapheresis
    leukapheresis
  • Drug: Busulfan
    Busulfan IV daily x 4 days (transplantation days -5,-4,-3,-2). The day -5 and -4 dose will be 130mg/m2
    Other Name: Busulfan (MyleranR, Busulfex™)
  • Procedure: Stem cell reinfusion
    autologous stem cell transplant
Autologous Hematopoietic Progenitor Cell Transplantation
G-CSF Mobilization Leukepheresis Busulfan Stem Cell Reinfusion
Interventions:
  • Drug: G-CSF
  • Drug: Leukapheresis
  • Drug: Busulfan
  • Procedure: Stem cell reinfusion
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
3
May 2009
May 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients must have had histologically confirmed diagnosis of AML, in 1st complete remission, by a pathologic review at the H. Lee Moffitt Cancer Center and Research Institute. Any induction/consolidation regimen is permitted.
  • General Inclusion Criteria:

    1. Age 56-74
    2. Able to give informed consent
    3. Hepatic and renal function: normal bilirubin, AST and ALT less than or equal to 2x normal limits, serum creatinine less than or equal to 1.5x normal
    4. Left ventricular ejection fraction (LVEF) must be in normal range
    5. FEV1 AND DLCO greater than or equal to 50% predicted (at planned time of transplantation)
    6. ECOG PS less than or equal to 2 (at planned time of transplantation)
  • Disease Specific Inclusion Criteria:

    1. Adverse-risk karyotype (del 5/5q, 7/7q, 3q, greater than or equal to 3 abnormalities):
    2. Intermediate-risk karyotype [46 XY, +8, -Y, +6, or any other isolated (<3 total) non-random abnormality not included in the adverse-risk category or favorable-risk category below]
  • AML arising from antecedent hematologic disorder (e.g. MDS)
  • Secondary AML (t-AML)

Exclusion Criteria:

  • Acute Promyelocytic Leukemia(FAB M3) subtype
  • Presence of (8;21) translocation or inversion 16/t(16;16) cytogenetic phenotype (i.e. favorable-risk AML)
  • Eligible for and willing to undergo matched-sibling allogeneic transplantation
  • Greater than 2 induction regimens required to achieve complete remission
  • Duration of > 8 weeks between completion of induction chemotherapy and initiation of consolidation chemotherapy
  • No prior malignancy is allowed, except for adequately treated basal cell (or squamous cell) skin cancer, in situ cervical cancer, or other cancer for which the patient has been disease-free for at least 5 years.
  • Prior extensive radiation therapy (>25% of bone marrow reserve)
  • Concomitant radiation therapy, chemotherapy, or immunotherapy
  • Intrinsic impaired organ function (as stated above)
  • Active infection
  • Positive serum pregnancy test in women who have not yet reached menopause (no menstrual periods for >12 months or who have not undergone tubal ligation or complete hysterectomy.
  • Women who are breast-feeding
  • Positive HIV testing
  • Presence of CNS leukemia
  • Uncontrolled insulin-dependent diabetes mellitus or uncompensated major thyroid or adrenal gland dysfunction
  • Physical or psychiatric conditions that in the estimation of the PI or his designee place the patient at high-risk of toxicity or non-compliance
Both
56 Years to 74 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00363467
MCC-14604
Yes
H. Lee Moffitt Cancer Center and Research Institute
H. Lee Moffitt Cancer Center and Research Institute
ESP Pharma
Principal Investigator: Jeffrey E Lancet, MD H. Lee Moffitt Cancer Center and Research Institute
H. Lee Moffitt Cancer Center and Research Institute
August 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP