Busulfan and Cyclophosphamide Followed By ALLO BMT

Busulfan and Cyclophosphamide Followed By Allogeneic Hematopoietic Cell Transplantation In Patients With Hematological Malignancies

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.

Study Overview

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.

Study Type

Interventional

Enrollment (Actual)

5

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Minnesota
      • Minneapolis, Minnesota, United States, 55455
        • Masonic Cancer Center, University of Minnesota

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 44 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Allogeneic Hematopoietic Stem Cell Transplant
Patients treated with Allopurinol, Keppra, Busulfan, Cyclophosphamide, Filgrastim, antithymocyte globulin, Tacrolimus, Mycophenolate mofetil and allogeneic hematopoietic stem cell transplant infusion.
Day -8 (prior to transplant): Per institutional guidelines
Other Names:
  • Zyloprim
  • Lopurin
Day -8 (prior to transplant): Per institutional guidelines
Other Names:
  • Levetiracetam
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 Names:
  • Myleran
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 Names:
  • Cytoxan
All patients (regardless of allograft source) will receive tacrolimus therapy beginning on day -3. Dosing will be monitored and altered as clinically appropriate per institutional pharmacy guidelines. Dose adjustments will be made on the basis of toxicity and/or low tacrolimus levels. Taper at day +100 for matched sibling donor (MSD) recipients, and day +180 for non-MSD recipients. Taper to zero by 10% weekly dose reduction over approximately 10 weeks.
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 Names:
  • MMF
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.
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
Administered per institutional guidelines for recipients of umbilical cord blood transplant.
Other Names:
  • ATG

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Counts of Participants With Disease Free Survival
Time Frame: 2 Years
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. Patients with leukemia involving the BM and myelodysplastic syndrome will have this assessed by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.
2 Years
Count of Participants With Disease Free Survival
Time Frame: 5 Years
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. Patients with leukemia involving the BM and myelodysplastic syndrome will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.
5 Years
Count of Participants With Disease Free Survival
Time Frame: 7 Years
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. Patients with leukemia involving the BM and myelodysplastic syndrome will have this done by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.
7 Years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Count of Participants Who Achieved Neutrophil Engraftment
Time Frame: By Day 42
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.
By Day 42
Percentage of Participants With Acute Graft-Versus-Host Disease by Grade
Time Frame: Day 100
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria used for staging. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level. The stages of individual organ involvement are combined to produce an overall grade. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
Day 100
Percentage of Participants With Chronic Graft-Versus-Host Disease
Time Frame: 6 Months
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level. The stages of individual organ involvement are combined to produce an overall grade. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
6 Months
Percentage of Participants With Chronic Graft-Versus-Host Disease
Time Frame: 1 Year
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host. Patients will be staged weekly between days 0 and 100 after transplantation using standard criteria used for staging. Patients will be assigned an overall GVHD score based on extent of skin rash, volume of diarrhea and maximum bilirubin level. The stages of individual organ involvement are combined to produce an overall grade. Grade I GVHD is characterized as mild disease, grade II GVHD as moderate, grade III as severe, and grade IV life-threatening.
1 Year
Percentage of Participants With Treatment-Related Toxicity
Time Frame: 6 Months
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
6 Months
Percentage of Participants With Treatment-Related Toxicity
Time Frame: 1 year
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
1 year
Percentage of Participants With Relapse
Time Frame: 1 Year
The return of disease after its apparent recovery/cessation. Patients with leukemia involving the BM and myelodysplastic syndrome will have this assessed by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.
1 Year
Percentage of Participants With Relapse
Time Frame: 2 Years
The return of disease after its apparent recovery/cessation. Patients with leukemia involving the BM and myelodysplastic syndrome will have this assessed by BM biopsy and additional special studies such as cytogenetics or flow cytometry as appropriate. Patients will also have radiology studies such as plain X-rays or CT scans and/or other studies such as blood tumor markers to document presence or absence of disease as clinically indicated.
2 Years
Percentage of Participants With Engraftment Failure
Time Frame: Day 42
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.
Day 42
Number of Participant Who Were Alive at 2 Years Post Transplant
Time Frame: 2 Years
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.
2 Years
Number of Participant Who Were Alive at 5 Years Post Transplant
Time Frame: 5 Years
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.
5 Years
Number of Participant Who Were Alive at 7 Years Post Transplant
Time Frame: 7 Years
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.
7 Years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Margaret L. MacMillan, M.D., Masonic Cancer Center, University of Minnesota

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2013

Primary Completion (Actual)

February 10, 2020

Study Completion (Actual)

February 10, 2020

Study Registration Dates

First Submitted

September 5, 2012

First Submitted That Met QC Criteria

September 13, 2012

First Posted (Estimate)

September 14, 2012

Study Record Updates

Last Update Posted (Actual)

April 13, 2021

Last Update Submitted That Met QC Criteria

March 17, 2021

Last Verified

March 1, 2021

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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