Clinical trial NCT01666080: Second or Greater Allogeneic Hematopoietic Stem Cell Transplant Using Reduced Intensity Conditioning (RIC)
Official title: Second or Greater Allogeneic Hematopoietic Stem Cell Transplant Using Reduced Intensity Conditioning (RIC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hematologic Disorders
Hemoglobinopathies
Immunodeficiencies
Keywords: second stem cell transplant
donor hematopoietic engraftment
hematopoietic stem cell transplantation
inherited metabolic disorder
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2012-08-16
Enrollment: 30
Sex: ALL
Maximum age (years): 55
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Time to Engraftment
timeFrame: Day 42
Secondary outcomes:
measure: Incidence of Graft Failure
timeFrame: Day 42
measure: Status of Donor Chimerism
timeFrame: Day 100, 6 Months, 1 Year
measure: Incidence of Acute Graft-Versus-Host Disease (GVHD)
timeFrame: Day 100
measure: Change in Incidence of Chronic Graft-Versus-Host Disease (GVHD)
timeFrame: 6 Months, 1 Year
measure: Incidence of Transplant Related Mortality
timeFrame: 6 Months
measure: Incidence of Overall Survival
timeFrame: 6 Months
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center, University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, University of Minnesota
name: Troy Lund, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: