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

NCT ID: NCT01666080

Last Updated: 2025-07-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-08-31
• Study Completion Date: 2027-06-30

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.

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.

Conditions

Hematologic Disorders; Hemoglobinopathies; Immunodeficiencies

Study Design

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

Study Groups

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.

Group Type: OTHER

Busulfan

Intervention Type: DRUG

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

Fludarabine

Intervention Type: DRUG

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

Total body irradiation

Intervention Type: RADIATION

200 cGy on Day -1

Stem cell transplant

Intervention Type: BIOLOGICAL

stem cell infusion on day 0

Keppra

Intervention Type: DRUG

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

Interventions

Busulfan

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

Intervention Type: DRUG

Fludarabine

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

Intervention Type: DRUG

Total body irradiation

200 cGy on Day -1

Intervention Type: RADIATION

Stem cell transplant

stem cell infusion on day 0

Intervention Type: BIOLOGICAL

Keppra

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

Intervention Type: DRUG

Other Intervention Names

Busulfex; Fludara; Levetiracetam

Eligibility Criteria

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.

• Maximum Eligible Age: 55 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

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

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

Masonic Cancer Center, University of Minnesota

Minneapolis, Minnesota, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

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

Role: CONTACT

mill4991@umn.edu

612-625-2508

Paul Orchard, M.D.

Role: CONTACT

orcha001@umn.edu

612-626-2313

Facility Contacts

Weston P. Miller, M.D.

Role: primary

mill4991@umn.eud

612-626-2778

Other Identifiers

MT2012-11C

Identifier Type: OTHER

Identifier Source: secondary_id

2012OC065

Identifier Type: -

Identifier Source: org_study_id