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

NCT01666080 | Recruiting

• 2 other identifiers: 2012OC065MT2012-11C
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hematologic Disorders; Hemoglobinopathies; Immunodeficiencies

Keywords

second stem cell transplant; donor hematopoietic engraftment; hematopoietic stem cell transplantation; inherited metabolic disorder

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Incidence of Graft Failure

  Day 42

• Status of Donor Chimerism

  Day 100, 6 Months, 1 Year

• Incidence of Acute Graft-Versus-Host Disease (GVHD)

  Day 100

• Change in Incidence of Chronic Graft-Versus-Host Disease (GVHD)

  6 Months, 1 Year

• Incidence of Transplant Related Mortality

  6 Months

Study Arms (1)

Reduced Intensity Conditioning

OTHER

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.

Drug: Busulfan; Drug: Fludarabine; Radiation: Total body irradiation; Biological: Stem cell transplant; Drug: Keppra

Interventions

Busulfan DRUG

0.4 mg/kg (0.5 mg/kg if \<4 years of age) intravenously (IV) every 6 hours on Days -8 and -7.

Also known as: Busulfex

Reduced Intensity Conditioning

Fludarabine DRUG

40 mg/m\^2 intravenously (IV) over 1 hour on days -6 through -2.

Also known as: Fludara

Reduced Intensity Conditioning

Total body irradiation RADIATION

200 cGy on Day -1

Reduced Intensity Conditioning

Stem cell transplant BIOLOGICAL

stem cell infusion on day 0

Reduced Intensity Conditioning

Keppra DRUG

Keppra will be given for seizure prophylaxis during busulfan administration as per the standard institutional protocol.

Also known as: Levetiracetam

Reduced Intensity Conditioning

Eligibility Criteria

• Age: Up to 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.
• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• Masonic Cancer Center, University of Minnesota: lead

Study Sites (1)

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, 55455, United States

RECRUITING

MeSH Terms

Conditions

Hematologic Diseases; Hemoglobinopathies; Immunologic Deficiency Syndromes

Interventions

Busulfan; fludarabine; fludarabine phosphate; Whole-Body Irradiation; Stem Cell Transplantation; Levetiracetam

Condition Hierarchy (Ancestors)

Hemic and Lymphatic Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Immune System Diseases

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Radiotherapy; Therapeutics; Investigative Techniques; Cell Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Transplantation; Surgical Procedures, Operative; Acetamides; Amides; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Troy Lund, M.D., Ph.D.

  Masonic Cancer Center, University of Minnesota

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Troy Lund, M.D., Ph.D.

CONTACT

612-625-2508; mill4991@umn.edu

Paul Orchard, M.D.

CONTACT

612-626-2313; orcha001@umn.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 31, 2012
• First Posted: August 16, 2012
• Study Start: August 1, 2012
• Primary Completion: June 1, 2026
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 24, 2025

Record last verified: 2025-07

Locations

US (1)