Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Busulfan and Cyclophosphamide Followed By ALLO BMT

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01685411
Recruitment Status : Terminated
First Posted : September 14, 2012
Results First Posted : April 13, 2021
Last Update Posted : April 13, 2021
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

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.

Condition or disease Intervention/treatment Phase
Acute Lymphoblastic Leukemia Acute Myeloid Leukemia Myelodysplastic Syndrome Drug: Allopurinol Drug: Keppra Drug: Busulfan Drug: Cyclophosphamide Drug: Tacrolimus Drug: Mycophenolate mofetil Biological: Allogeneic hematopoietic stem cell transplant Biological: Filgrastim Biological: antithymocyte globulin Not Applicable

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Busulfan and Cyclophosphamide Followed By Allogeneic Hematopoietic Cell Transplantation In Patients With Hematological Malignancies
Study Start Date : January 2013
Actual Primary Completion Date : February 10, 2020
Actual Study Completion Date : February 10, 2020


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.
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: Tacrolimus
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.

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




Primary Outcome Measures :
  1. 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. 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.

  3. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.



Information from the National Library of Medicine

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, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   up to 44 Years   (Child, Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01685411


Locations
Layout table for location information
United States, Minnesota
Masonic Cancer Center, University of Minnesota
Minneapolis, Minnesota, United States, 55455
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Layout table for investigator information
Principal Investigator: Margaret L. MacMillan, M.D. Masonic Cancer Center, University of Minnesota
  Study Documents (Full-Text)

Documents provided by Masonic Cancer Center, University of Minnesota:
Layout table for additonal information
Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01685411    
Other Study ID Numbers: 2011OC139
MT2011-20C ( Other Identifier: Blood and Marrow Transplantation Program )
First Posted: September 14, 2012    Key Record Dates
Results First Posted: April 13, 2021
Last Update Posted: April 13, 2021
Last Verified: March 2021
Additional relevant MeSH terms:
Layout table for MeSH terms
Leukemia
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Neoplasms
Bone Marrow Diseases
Hematologic Diseases
Leukemia, Lymphoid
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Mycophenolic Acid
Cyclophosphamide
Busulfan
Allopurinol
Levetiracetam
Tacrolimus
Antilymphocyte Serum
Lenograstim
Sargramostim
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists