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

Sponsor

Masonic Cancer Center, University of Minnesota (Other)

Overall Status

Recruiting

CT.gov ID

NCT01666080

Collaborator

(none)

Enrollment

Location

Arm

118

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hematologic Disorders Hemoglobinopathies Immunodeficiencies	Drug: Busulfan Drug: Fludarabine Radiation: Total body irradiation Biological: Stem cell transplant Drug: Keppra	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

30 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Aug 1, 2012

Anticipated Primary Completion Date :

Jun 1, 2022

Anticipated Study Completion Date :

Jun 1, 2022

Arms and Interventions

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.	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 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. Other Names: Levetiracetam

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.

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

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.

Other Names:

Levetiracetam

Outcome Measures

Primary Outcome Measures

Time to Engraftment [Day 42]
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.

Secondary Outcome Measures

Incidence of Graft Failure [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.
Status of Donor Chimerism [Day 100, 6 Months, 1 Year]
A state in bone marrow transplantation in which donor hematopoietic cells and host cells exist compatibly without signs of rejection.
Incidence of Acute Graft-Versus-Host Disease (GVHD) [Day 100]
Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.
Change in Incidence of Chronic Graft-Versus-Host Disease (GVHD) [6 Months, 1 Year]
Chronic Graft-Versus-Host Disease is a severe long-term complication created by infusion of donor cells into a foreign host.
Incidence of Transplant Related Mortality [6 Months]
In the field of transplantation, toxicity is high and all deaths without previous relapse or progression are usually considered as related to transplantation.
Incidence of Overall Survival [6 Months]
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 55 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.