Busulfan and Cyclophosphamide Followed By ALLO BMT - Full Text View

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:

Genetics Home Reference related topics: core binding factor acute myeloid leukemia cytogenetically normal acute myeloid leukemia familial acute myeloid leukemia with mutated CEBPA

Drug Information available for: Cyclophosphamide Busulfan Allopurinol Allopurinol sodium Mycophenolic acid Mycophenolate sodium Cyclosporine Levetiracetam Mycophenolate mofetil hydrochloride Filgrastim Mycophenolate mofetil Lenograstim Granulocyte colony-stimulating factor Antilymphocyte Serum

Genetic and Rare Diseases Information Center resources: Myeloid Leukemia Myelodysplastic Syndromes Acute Myeloid Leukemia Acute Non Lymphoblastic Leukemia Acute Lymphoblastic Leukemia Lymphosarcoma

U.S. FDA Resources

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 2025
Estimated Primary Completion Date:	September 2025 (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

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 (Child, Adult)
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


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:	August 15, 2016
Health Authority:	United States: Institutional Review Board

Additional relevant MeSH terms:


Leukemia Leukemia, Myeloid, Acute Myelodysplastic Syndromes Preleukemia Precursor Cell Lymphoblastic Leukemia-Lymphoma Leukemia, Lymphoid Neoplasms by Histologic Type Neoplasms Leukemia, Myeloid Bone Marrow Diseases Hematologic Diseases Precancerous Conditions Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders	Immune System Diseases Cyclophosphamide Cyclosporins Cyclosporine Mycophenolate mofetil Busulfan Antilymphocyte Serum Allopurinol Mycophenolic Acid Lenograstim Etiracetam Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents

ClinicalTrials.gov processed this record on September 28, 2016