Busulfan and Cyclophosphamide Followed By ALLO BMT

NCT ID: NCT01685411

Last Updated: 2021-04-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-01-31
• Study Completion Date: 2020-02-10

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.

Conditions

Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; Myelodysplastic Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Allopurinol

Intervention Type: DRUG

Day -8 (prior to transplant): Per institutional guidelines

Keppra

Intervention Type: DRUG

Day -8 (prior to transplant): Per institutional guidelines

Busulfan

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Intervention Type: DRUG

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.

Allogeneic hematopoietic stem cell transplant

Intervention Type: BIOLOGICAL

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

Intervention Type: BIOLOGICAL

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

Intervention Type: BIOLOGICAL

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

Interventions

Allopurinol

Day -8 (prior to transplant): Per institutional guidelines

Intervention Type: DRUG

Keppra

Day -8 (prior to transplant): Per institutional guidelines

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

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.

Intervention Type: 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.

Intervention Type: BIOLOGICAL

antithymocyte globulin

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

Intervention Type: BIOLOGICAL

Other Intervention Names

Lopurin; Zyloprim; Levetiracetam; Myleran; Cytoxan; MMF; G-CSF; Granulocyte-colony stimulating factor; ATG

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

• Maximum Eligible Age: 44 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Margaret L. MacMillan, M.D.

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

MT2011-20C

Identifier Type: OTHER

Identifier Source: secondary_id

2011OC139

Identifier Type: -

Identifier Source: org_study_id