Busulfan and Cyclophosphamide Followed By ALLO BMT

Acute Myeloid Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01685411
• Other study ID #: 2011OC139
• Secondary ID: MT2011-20C
• Status: Terminated
• Phase: N/A
• Start date: January 2013
• Est. completion date: February 10, 2020

Study information

• Verified date: March 2021
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: February 10, 2020
• Est. primary completion date: February 10, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 44 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lymphoblastic Leukemia
• Acute Myeloid Leukemia
• Leukemia
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma

Intervention

Drug:
• Allopurinol
Day -8 (prior to transplant): Per institutional guidelines
• Keppra
Day -8 (prior to transplant): Per institutional guidelines
• 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.
• 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.
• 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.
• 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.

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.
• 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.
• antithymocyte globulin
Administered per institutional guidelines for recipients of umbilical cord blood transplant.

Locations

Country	Name	City	State
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	2 Years
Primary	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.	5 Years
Primary	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.	7 Years
Secondary	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.	By Day 42
Secondary	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.	Day 100
Secondary	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.	6 Months
Secondary	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.	1 Year
Secondary	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.	6 Months
Secondary	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.	1 year
Secondary	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.	1 Year
Secondary	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.	2 Years
Secondary	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.	Day 42
Secondary	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.	2 Years
Secondary	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.	5 Years
Secondary	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.	7 Years