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

Hemoglobinopathies Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01666080
• Other study ID #: 2012OC065
• Secondary ID: MT2012-11C
• Status: Recruiting
• Phase: N/A
• Start date: August 2012
• Est. completion date: June 2024

Study information

• Verified date: February 2024
• Source: Masonic Cancer Center, University of Minnesota
• Contact: Troy Lund, M.D., Ph.D.
• Phone: 612-625-2508
• Email: mill4991[@]umn.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 2024
• Est. primary completion date: June 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 55 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hematologic Diseases
• Hematologic Disorders
• Hemoglobinopathies
• Immunodeficiencies

Intervention

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

Radiation:
• Total body irradiation
200 cGy on Day -1

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.

Locations

Country	Name	City	State
United States	Masonic Cancer Center, University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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