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Busulfan and Cyclophosphamide Followed By ALLO BMT

Primary Purpose

Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Myelodysplastic Syndrome

Status
Terminated
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Allopurinol
Keppra
Busulfan
Cyclophosphamide
Tacrolimus
Mycophenolate mofetil
Allogeneic hematopoietic stem cell transplant
Filgrastim
antithymocyte globulin
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Acute Lymphoblastic Leukemia

Eligibility Criteria

undefined - 44 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Masonic Cancer Center, University of Minnesota

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Allogeneic Hematopoietic Stem Cell Transplant

Arm Description

Patients treated with Allopurinol, Keppra, Busulfan, Cyclophosphamide, Filgrastim, antithymocyte globulin, Tacrolimus, Mycophenolate mofetil and allogeneic hematopoietic stem cell transplant infusion.

Outcomes

Primary Outcome Measures

Counts of Participants With Disease Free Survival
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.
Count of Participants With Disease Free Survival
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.
Count of Participants With Disease Free Survival
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.

Secondary Outcome Measures

Count of Participants Who Achieved Neutrophil Engraftment
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.
Percentage of Participants With Acute Graft-Versus-Host Disease by Grade
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.
Percentage of Participants With Chronic Graft-Versus-Host Disease
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.
Percentage of Participants With Chronic Graft-Versus-Host Disease
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.
Percentage of Participants With Treatment-Related Toxicity
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Percentage of Participants With Treatment-Related Toxicity
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Percentage of Participants With Relapse
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.
Percentage of Participants With Relapse
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.
Percentage of Participants With Engraftment Failure
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.
Number of Participant Who Were Alive at 2 Years Post Transplant
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.
Number of Participant Who Were Alive at 5 Years Post Transplant
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.
Number of Participant Who Were Alive at 7 Years Post Transplant
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.

Full Information

First Posted
September 5, 2012
Last Updated
March 17, 2021
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT01685411
Brief Title
Busulfan and Cyclophosphamide Followed By ALLO BMT
Official Title
Busulfan and Cyclophosphamide Followed By Allogeneic Hematopoietic Cell Transplantation In Patients With Hematological Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
March 2021
Overall Recruitment Status
Terminated
Study Start Date
January 2013 (undefined)
Primary Completion Date
February 10, 2020 (Actual)
Study Completion Date
February 10, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia, Acute Myeloid Leukemia, Myelodysplastic Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Allogeneic Hematopoietic Stem Cell Transplant
Arm Type
Experimental
Arm Description
Patients treated with Allopurinol, Keppra, Busulfan, Cyclophosphamide, Filgrastim, antithymocyte globulin, Tacrolimus, Mycophenolate mofetil and allogeneic hematopoietic stem cell transplant infusion.
Intervention Type
Drug
Intervention Name(s)
Allopurinol
Other Intervention Name(s)
Lopurin, Zyloprim
Intervention Description
Day -8 (prior to transplant): Per institutional guidelines
Intervention Type
Drug
Intervention Name(s)
Keppra
Other Intervention Name(s)
Levetiracetam
Intervention Description
Day -8 (prior to transplant): Per institutional guidelines
Intervention Type
Drug
Intervention Name(s)
Busulfan
Other Intervention Name(s)
Myleran
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Tacrolimus
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Mycophenolate mofetil
Other Intervention Name(s)
MMF
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Allogeneic hematopoietic stem cell transplant
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
Filgrastim
Other Intervention Name(s)
G-CSF, Granulocyte-colony stimulating factor
Intervention Description
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.
Intervention Type
Biological
Intervention Name(s)
antithymocyte globulin
Other Intervention Name(s)
ATG
Intervention Description
Administered per institutional guidelines for recipients of umbilical cord blood transplant.
Primary Outcome Measure Information:
Title
Counts of Participants With Disease Free Survival
Description
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.
Time Frame
2 Years
Title
Count of Participants With Disease Free Survival
Description
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.
Time Frame
5 Years
Title
Count of Participants With Disease Free Survival
Description
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.
Time Frame
7 Years
Secondary Outcome Measure Information:
Title
Count of Participants Who Achieved Neutrophil Engraftment
Description
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.
Time Frame
By Day 42
Title
Percentage of Participants With Acute Graft-Versus-Host Disease by Grade
Description
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.
Time Frame
Day 100
Title
Percentage of Participants With Chronic Graft-Versus-Host Disease
Description
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.
Time Frame
6 Months
Title
Percentage of Participants With Chronic Graft-Versus-Host Disease
Description
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.
Time Frame
1 Year
Title
Percentage of Participants With Treatment-Related Toxicity
Description
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Time Frame
6 Months
Title
Percentage of Participants With Treatment-Related Toxicity
Description
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Time Frame
1 year
Title
Percentage of Participants With Relapse
Description
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.
Time Frame
1 Year
Title
Percentage of Participants With Relapse
Description
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.
Time Frame
2 Years
Title
Percentage of Participants With Engraftment Failure
Description
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.
Time Frame
Day 42
Title
Number of Participant Who Were Alive at 2 Years Post Transplant
Description
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.
Time Frame
2 Years
Title
Number of Participant Who Were Alive at 5 Years Post Transplant
Description
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.
Time Frame
5 Years
Title
Number of Participant Who Were Alive at 7 Years Post Transplant
Description
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.
Time Frame
7 Years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
44 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Margaret L. MacMillan, M.D.
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
Masonic Cancer Center, University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Busulfan and Cyclophosphamide Followed By ALLO BMT

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