Second or Greater Allogeneic Hematopoietic Stem Cell Transplant Using Reduced Intensity Conditioning (RIC)

This is a treatment guideline for a second or greater allogeneic hematopoietic stem cell transplant (HSCT) using a reduced intensity conditioning (RIC) in patients with non-malignant or malignant diseases. This regimen, consisting of busulfan, fludarabine, and low dose total body irradiation (TBI), is designed to promote engraftment in patients who failed to achieve an acceptable level of donor-derived engraftment following a previous allogeneic HCT.

Study Overview

• Status: Recruiting
• Conditions: Hemoglobinopathies; Immunodeficiencies; Hematologic Disorders
• Intervention / Treatment: Radiation: Total body irradiation; Drug: Busulfan; Drug: Fludarabine; Biological: Stem cell transplant; Drug: Keppra

Detailed Description

There is no research element except the collection of routine clinical data. Patients will consent to allow routine clinical data to be collected and maintained in OnCore, the Masonic Cancer Center's (MCC) clinical database, and specific transplant related endpoints in the University Of Minnesota Blood and Bone Marrow Database as part of the historical database maintained by the department.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Troy Lund, M.D., Ph.D.; Phone Number: 612-625-2508; Email: mill4991@umn.edu
• Study Contact Backup: Name: Paul Orchard, M.D.; Phone Number: 612-626-2313; Email: orcha001@umn.edu

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Recruiting
      • Masonic Cancer Center, University of Minnesota
      • Contact: Weston P. Miller, M.D.; Phone Number: 612-626-2778; Email: mill4991@umn.eud
      • Principal Investigator: Weston P. Miller, M.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 55 years (Child, Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of any disease for which a second or greater hematopoietic stem cell transplant is needed due to insufficient donor chimerism following hematopoietic recovery after previous HSCT. Determination of "insufficiency of donor chimerism" will be made by the treating transplant physician. Occasionally donor derived engraftment may be present, but sustained aplasia or failed recovery of sufficient hematopoiesis requires administration of a second graft. This intervention may be used for both situations.

• Donor Availability: Patients considered for transplantation must have a sufficient graft as based on current criteria of the University of Minnesota Blood and Marrow Transplantation Program

  • Transplantation using sufficiently matched related donors (such as matched siblings) or unrelated donors will be considered. Both granulocyte-colony stimulating factor (GCSF) stimulated peripheral blood grafts and bone marrow grafts will be considered, although bone marrow will be the priority.
  • Cord blood grafts, both related and unrelated, are also eligible. As this protocol will use a reduced intensity regimen, this protocol will use the current recommendations of the University of Minnesota for choosing cord blood grafts. If a single cord blood unit cell dose is insufficient, double cord transplantation should be considered if sufficiently matched cord blood units are available. The priority of choosing cord blood donors is based on the current institutional recommendations.
  • Exclusion of Metabolic Disorder or other Inherited Disorder Carrier Status from related donor and unrelated cord blood grafts as appropriate for primary disease.

At the discretion of the treating transplant physician, an allograft from the previous donor may be used, if available.

• Age, Performance Status, Consent

  • Age: 0 to 55 years
  • Consent: voluntary written consent (adult or parental/guardian)

Exclusion Criteria:

• Previous irradiation that precludes the safe administration of an additional dose of 200 cGy of total body irradiation (TBI). Radiation Oncology will evaluate all patients who have had previous radiation therapy or TBI for approval to receive an additional 200 cGy of TBI
• Pregnant or breastfeeding
• Active, uncontrolled infection - infection that is stable or improving after 1 week of appropriate therapy (4 weeks for presumed or documented fungal infections) will be permitted
• HIV positive
• While it would be advantageous to begin therapy on this second transplant regimen > 6 months following a prior myeloablative regimen or >2 months after a reduced intensity regimen, it is recognized that there are circumstances where this may not be practical.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Reduced Intensity Conditioning; Includes patients receiving a second or greater allogeneic hematopoietic stem cell transplant (HSCT) using reduced intensity conditioning (RIC). Patients will receive busulfan, fludarabine, total body irradiation and stem cell transplant. Keppra will be given for seizure prophylaxis.

Radiation: Total body irradiation; 200 cGy on Day -1; Drug: Busulfan; 0.4 mg/kg (0.5 mg/kg if <4 years of age) intravenously (IV) every 6 hours on Days -8 and -7.; Other Names: Busulfex; Drug: Fludarabine; 40 mg/m^2 intravenously (IV) over 1 hour on days -6 through -2.; Other Names: Fludara; Biological: Stem cell transplant; stem cell infusion on day 0; Drug: Keppra; Keppra will be given for seizure prophylaxis during busulfan administration as per the standard institutional protocol.; Other Names: Levetiracetam

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Engraftment	Neutrophil engraftment is defined as the first day of three consecutive days where the neutrophil count (absolute neutrophil count) is 500 cells/mm3 (0.5 x 109/L) or greater.	Day 42

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Graft 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
Status of Donor Chimerism	A state in bone marrow transplantation in which donor hematopoietic cells and host cells exist compatibly without signs of rejection.	Day 100, 6 Months, 1 Year
Incidence of Acute Graft-Versus-Host Disease (GVHD)	Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.	Day 100
Change in Incidence of Chronic Graft-Versus-Host Disease (GVHD)	Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.	6 Months, 1 Year
Incidence of Transplant Related Mortality	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
Incidence of Overall Survival	The percentage of people in a study or treatment group who are alive for a certain period of time after they were diagnosed with or treated for a disease. Also called survival rate. 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.	6 Months

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota
• Investigators: Principal Investigator: Troy Lund, M.D., Ph.D., Masonic Cancer Center, University of Minnesota

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2012
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2024

Study Registration Dates

• First Submitted: July 31, 2012
• First Submitted That Met QC Criteria: August 14, 2012
• First Posted (Estimated): August 16, 2012

Study Record Updates

• Last Update Posted (Estimated): February 29, 2024
• Last Update Submitted That Met QC Criteria: February 27, 2024
• Last Verified: February 1, 2024

More Information

Terms related to this study

• Keywords: hematopoietic stem cell transplantation; second stem cell transplant; donor hematopoietic engraftment; inherited metabolic disorder
• Additional Relevant MeSH Terms: Genetic Diseases, Inborn; Hematologic Diseases; Hemoglobinopathies; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Anticonvulsants; Nootropic Agents; Fludarabine; Busulfan; Levetiracetam
• Other Study ID Numbers: 2012OC065; MT2012-11C (Other Identifier: Blood and Marrow Transplantation Program)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No