Busulfan and Cyclophosphamide Followed By ALLO BMT

• ClinicalTrials.gov Identifier: NCT01685411
• Recruitment Status: Recruiting
• First Posted: September 14, 2012
• Last Update Posted: September 26, 2019
• Sponsor: Masonic Cancer Center, University of Minnesota
• Information provided by (Responsible Party): Masonic Cancer Center, University of Minnesota

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.

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. Results will be compared to historical controls.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 30 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
• Estimated Primary Completion Date: September 2025
• Estimated Study Completion Date: September 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.
3. Disease Free Survival [ Time Frame: 10 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.

Secondary Outcome Measures :

1. Days to 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. Incidence of Acute Graft-Versus-Host Disease [ 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.
3. Incidence of Chronic Graft-Versus-Host Disease [ Time Frame: 6 Months and 1 Year ]
   Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
4. Incidence of Treatment-Related Toxicity [ Time Frame: 6 Months and 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.
5. Incidence of Relapse [ Time Frame: 1 Year and 2 Years ]
   The return of disease after its apparent recovery/cessation.
6. Incidence of 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.
7. Overall Survival [ Time Frame: 2 Years, 5 Years and 10 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.

Eligibility Criteria

• 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

Contacts and Locations

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
• Other Study ID Numbers: 2011OC139; MT2011-20C ( Other Identifier: Blood and Marrow Transplantation Program )
• First Posted: September 14, 2012
• Last Update Posted: September 26, 2019
• Last Verified: September 2019

Additional relevant 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