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Busulfan and Fludarabine Followed by Post-transplant Cyclophosphamide

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier:
NCT00800839
First received: December 1, 2008
Last updated: July 28, 2016
Last verified: July 2016
  Purpose
The goal of this clinical research study is to learn if cyclophosphamide given after busulfan and fludarabine can help to prevent graft versus host disease (GVHD - a condition in which transplanted tissue attacks the body into which it is transplanted) in patients receiving a stem cell transplant. The safety of this drug combination will also be studied.

Condition Intervention Phase
Hematologic Diseases
Leukemia
Lymphoma
Myeloma
Drug: Busulfan
Drug: Fludarabine
Drug: Cyclophosphamide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Busulfan (IV) and Fludarabine Followed by Post-allogeneic Transplantation Cyclophosphamide for Graft-versus-Host Disease Prophylaxis in Patients With Hematologic Malignancies.

Resource links provided by NLM:


Further study details as provided by M.D. Anderson Cancer Center:

Primary Outcome Measures:
  • Cumulative Incidence of Grade II to IV Acute GVHD [ Time Frame: 100 days post transplant ] [ Designated as safety issue: Yes ]
    Graft Versus Host Disease (GVHD) defined as grade 2 to 4 GVHD within first 100 days post transplant. Death or disease progression before diagnosis of GVHD were considered competing risks in the estimation of the incidence of acute GVHD.

  • Cumulative Incidence of Grade III to IV Acute GVHD [ Time Frame: 100 days post transplant ] [ Designated as safety issue: Yes ]
    Graft Versus Host Disease (GVHD) defined as grade 3 to 4 GVHD within first 100 days post transplant. Death or disease progression before diagnosis of GVHD were considered competing risks in the estimation of the incidence of acute GVHD.

  • Day-100 Treatment-Related Mortality [ Time Frame: 100 days post transplant ] [ Designated as safety issue: No ]
    Treatment-Related Mortality (TRM) was estimated from the date of transplant using the cumulative incidence method to account for competing risks. Disease progression or relapse death were considered competing risk for TRM.


Secondary Outcome Measures:
  • Rate of Engraftment [ Time Frame: From engraftment to 60 days post transplant ] [ Designated as safety issue: No ]
    Engraftment defined as the evidence of donor derived cells (more than 5%) by bone marrow chimerism studies in the presence of neutrophil recovery by day 28 post stem cell (SC) infusion. Engraftment date is the first day of three (3) consecutive days that the ANC exceeds 0.5 x109/L. Delayed engraftment is defined as the evidence of engraftment beyond day 28 post SC infusion achieved after the administration of therapeutic (high dose) hematopoietic growth factors.

  • 2-year Progression-Free Survival [ Time Frame: First 25-35 days post transplant and then every 3 months for a maximum of 2 years ] [ Designated as safety issue: No ]
    Progression-free survival (PFS) is defined as the interval between day of transplant and day of death or disease progression.

  • 2-year Overall Survival [ Time Frame: First 25-35 days post transplant and then every 3 months for a maximum of 2 years ] [ Designated as safety issue: No ]
    Overall Survival (OS) is defined as the interval between day of transplant and day of death.


Enrollment: 56
Study Start Date: September 2008
Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Busulfan + Fludarabine + Cyclophosphamide
Busulfan starting dose of 32 mg/m^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3. Fludarabine dose of 40 mg/m^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan. Cyclophosphamide dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.
Drug: Busulfan
Starting dose of 32 mg/m^2 by vein over 3 hours each day. Test dose day -8 (inpatient) or test dose day -30 to day -8 (outpatient) and then, days -6,-5,-4, and -3.
Other Names:
  • Bulsulfex™
  • Myleran®
Drug: Fludarabine
Dose of 40 mg/m^2 by vein over 1 hour each day on Day -6 through Day -3 before receiving Busulfan.
Other Names:
  • Fludarabine Phosphate
  • Fludara
Drug: Cyclophosphamide
Dose of 50 mg/kg by vein over 3 hours on Days 3 and 4.
Other Names:
  • Cytoxan®
  • Neosar®

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   6 Months to 75 Years   (Child, Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patients with high risk hematological malignancies, including those with induction failure and after treated or untreated relapse.
  2. HLA-identical sibling or matched unrelated donor transplants not eligible for protocols of higher priority.
  3. Age 6 months to 75 years.
  4. Bilirubin </= 1.5 mg/dl, serum glutamate pyruvate transaminase (SGPT) </= 200 IU/ml (unless Gilbert's syndrome).
  5. Calculated creatinine clearance of >50mL/min using the Cockcroft-Gault equation for adult patients 18 to 70 years old, and the Schwartz equation for pediatric patients 6 months to 17 years old.
  6. Diffusing capacity for carbon monoxide (DLCO) >45% predicted corrected for hemoglobin (as reported by the Pulmonary Function Laboratory at MDACC). For most children </= 6 years of age who are unable to perform pulmonary function test (PFT), pulse oximetry >/= 92% on room air.
  7. left ventricular ejection fraction (LVEF) >/= 35%.

Exclusion Criteria:

  1. HIV seropositivity
  2. Uncontrolled infections.
  3. Positive Beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization
  4. Inability to sign consent
  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: NCT00800839

Locations
United States, Texas
University of Texas MD Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
Principal Investigator: Amin Alousi, MD M.D. Anderson Cancer Center
  More Information

Additional Information:
Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT00800839     History of Changes
Other Study ID Numbers: 2008-0261  NCI-2012-01660 
Study First Received: December 1, 2008
Results First Received: July 28, 2016
Last Updated: July 28, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by M.D. Anderson Cancer Center:
Post-allogeneic transplantation
Graft-versus-Host Disease Prophylaxis
Graft-versus-Host Disease
GVHD
Hematologic malignancies
Leukemia
Lymphoma
Myeloma
Human Leukocyte Antigen
HLA
Busulfan
Cyclophosphamide
Fludarabine
Mesna
Cytoxan®
Neosar®
Busulfex
Myleran®
Fludarabine Phosphate

Additional relevant MeSH terms:
Graft vs Host Disease
Hematologic Diseases
Immune System Diseases
Cyclophosphamide
Fludarabine phosphate
Busulfan
Fludarabine
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on December 08, 2016