Busulfan and Cyclophosphamide Followed By ALLO BMT

This study is currently recruiting participants. (see Contacts and Locations)
Verified March 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT01685411
First received: September 5, 2012
Last updated: March 4, 2014
Last verified: March 2014
  Purpose

This is a treatment guideline to allow routine clinical data to be collected and maintained in Oncore (clinical database) and the University of Minnesota Blood and Marrow Database as part of the historical database maintained by the department.


Condition Intervention
Acute Lymphoblastic Leukemia
Acute Myeloid Leukemia
Myelodysplastic Syndrome
Drug: Allopurinol
Drug: Keppra
Drug: Busulfan
Drug: Cyclophosphamide
Drug: Cyclosporine A
Drug: Mycophenolate mofetil
Biological: Allogeneic hematopoietic stem cell transplant
Biological: Filgrastim
Biological: antithymocyte globulin

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Busulfan and Cyclophosphamide Followed By Allogeneic Hematopoietic Cell Transplantation In Patients With Hematological Malignancies

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Disease Free Survival [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.

  • Disease Free Survival [ Time Frame: 5 Years ] [ Designated as safety issue: No ]
    The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.

  • Disease Free Survival [ Time Frame: 10 Years ] [ Designated as safety issue: No ]
    The length of time after treatment ends that a patient survives without any signs or symptoms of that cancer or any other type of cancer. In a clinical trial, measuring the disease-free survival is one way to see how well a new treatment works.


Secondary Outcome Measures:
  • Days to Neutrophil Engraftment [ Time Frame: By Day 42 ] [ Designated as safety issue: No ]
    Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm^3 (0.5 x 10^9/L) or greater.

  • Incidence of Acute Graft-Versus-Host Disease [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
    Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.

  • Incidence of Chronic Graft-Versus-Host Disease [ Time Frame: 6 Months and 1 Year ] [ Designated as safety issue: Yes ]
    Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.

  • Incidence of Treatment-Related Toxicity [ Time Frame: 6 Months and 1 Year ] [ Designated as safety issue: Yes ]
    In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.

  • Incidence of Relapse [ Time Frame: 1 Year and 2 Years ] [ Designated as safety issue: No ]
    The return of disease after its apparent recovery/cessation.

  • Incidence of Engraftment Failure [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    Graft failure is defined as not accepting donated cells. The donated cells do not make the new white blood cells, red blood cells and platelets.

  • Overall Survival [ Time Frame: 2 Years, 5 Years and 10 Years ] [ Designated as safety issue: No ]
    Overall survival will be defined as time from date of enrollment to date of death or censored at the date of last documented contact for patients still alive.


Estimated Enrollment: 30
Study Start Date: January 2013
Estimated Study Completion Date: September 2022
Estimated Primary Completion Date: September 2022 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Allogeneic Hematopoietic Stem Cell Transplant
Patients treated with Allopurinol, Keppra, Busulfan, Cyclophosphamide, Filgrastim, antithymocyte globulin, cyclosporine A, Mycophenolate mofetil and allogeneic hematopoietic stem cell transplant infusion.
Drug: Allopurinol
Day -8 (prior to transplant): Per institutional guidelines
Other Names:
  • Lopurin
  • Zyloprim
Drug: Keppra
Day -8 (prior to transplant): Per institutional guidelines
Other Name: Levetiracetam
Drug: Busulfan
Days -7 through -4 (prior to transplant): given intravenously (IV) infusion over 2 hours every 6 hours following dose, administration and pharmacokinetic monitoring per University of Minnesota institutional guidelines.
Other Name: Myleran
Drug: Cyclophosphamide
Days -3 and -2 (prior to transplantation): given as a 2 hour intravenous infusion with a high volume fluid flush and mesna per institutional guidelines. Dosing is based on actual body weight.
Other Name: Cytoxan
Drug: Cyclosporine A
Day -3 (prior to transplant) and will be administered by mouth/intravenously (PO/IV) maintaining a trough level between 200 and 400 ng/mL. Adult initial dose will be 2.5 mg/kg IV over 2 hours every 12 hours. Children < 40 kg will be 2.5 mg/kg IV over 2 hours every 8 hours.
Other Name: CSA
Drug: Mycophenolate mofetil
Day -3 (prior to transplant): Recipients of umbilical cord blood will given a dose of 3 gm/day every 8 or 12 hours (> or = 40 kg) or 15 mg/kg 3 times per day (< 40 kg) for up to 30 days unless no engraftment.
Other Name: MMF
Biological: Allogeneic hematopoietic stem cell transplant
Day 0 (or Day+1/+2 to accommodate weekdays): Infusion of cells from related or unrelated donor bone marrow or single or double unrelated donor umbilical cord blood.
Biological: Filgrastim
Beginning Day +1: Intravenously (IV) 5 mcg/kg once daily and continuing until the absolute neutrophil count is >2500 x 10^9/L or per institutional guidelines.
Other Names:
  • G-CSF
  • Granulocyte-colony stimulating factor
Biological: antithymocyte globulin
Administered per institutional guidelines for recipients of umbilical cord blood transplant.
Other Name: ATG

Detailed Description:

This is a single arm trial to evaluate the efficacy of busulfan and cyclophosphamide followed by an allogeneic hematopoietic stem cell transplant (HSCT) in the treatment of hematological malignancies. The intent of this study is to provide a protocol that will use unmanipulated allogeneic hematopoietic stem cells from related and unrelated donors after a common preparative regimen. Results will be compared to historical controls.

  Eligibility

Ages Eligible for Study:   up to 44 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of acute lymphoblastic leukemia (ALL), acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) and current in complete remission meeting one of the following:

    • <45 years of age who are at least 6 months after initial hematopoietic stem cell transplant (HSCT)
    • <45 years of age and have received sufficient radiation treatment to be ineligible for total body irradiation (TBI) containing preparative therapy
  • Karnofsky performance status >70% or if <16 years of age, a Lansky play score >50
  • Adequate major organ function including:

    • cardiac: left ventricular ejection fraction >45% by echocardiogram (ECHO/MUGA)
    • renal: creatinine clearance >40 mL/min/1.73m^2
    • hepatic: no clinical evidence of hepatic failure (e.g., coagulopathy, ascites)
  • An acceptable source of stem cells according to current University of Minnesota Bone Marrow Transplant program guidelines. Acceptable stem cell sources include:

    • HLA-matched related or unrelated donor bone marrow (6/6 or 5/6 antigen match)
    • HLA-matched related or unrelated donor peripheral blood stem cells
    • related or single or double unrelated donor umbilical cord blood (6/6, 5/6 or 4/6 match)
  • Women of childbearing age must have a negative pregnancy test and all sexually active participants must agree to use effective contraception during study treatment
  • Written consent (adult or parent/guardian)

Exclusion Criteria:

  • eligible for TBI containing preparative regimen
  • active uncontrolled infection within one week of study enrollment
  • pregnant or lactating female
  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: NCT01685411

Contacts
Contact: Margaret L. MacMillan, M.D. 612-626-2778 macmi002@umn.edu

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Margaret L. MacMillan, M.D.    612-626-2778    macmi002@umn.edu   
Principal Investigator: Margaret L. MacMillan, M.D.         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Margaret L. MacMillan, M.D. Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01685411     History of Changes
Other Study ID Numbers: 2011OC139, MT2011-20C
Study First Received: September 5, 2012
Last Updated: March 4, 2014
Health Authority: United States: Institutional Review Board

Additional relevant MeSH terms:
Leukemia
Leukemia, Lymphoid
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Myelodysplastic Syndromes
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Precancerous Conditions
Allopurinol
Antilymphocyte Serum
Busulfan
Cyclophosphamide
Cyclosporine
Cyclosporins
Lenograstim
Mycophenolate mofetil
Mycophenolic Acid
Adjuvants, Immunologic
Alkylating Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on October 29, 2014