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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT01666080
First received: July 31, 2012
Last updated: May 15, 2014
Last verified: May 2014
  Purpose

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 Intervention
Hematologic Disorders
Hemoglobinopathies
Immunodeficiencies
Drug: Busulfan
Drug: Fludarabine
Radiation: Total body irradiation
Biological: Stem cell transplant
Drug: Keppra

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Second or Greater Allogeneic Hematopoietic Stem Cell Transplant Using Reduced Intensity Conditioning (RIC)

Resource links provided by NLM:


Further study details as provided by Masonic Cancer Center, University of Minnesota:

Primary Outcome Measures:
  • Time to Engraftment [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 42 ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 100, 6 Months, 1 Year ] [ Designated as safety issue: No ]
    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) [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: 6 Months, 1 Year ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 6 Months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 6 Months ] [ Designated as safety issue: No ]

    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.



Estimated Enrollment: 30
Study Start Date: August 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Busulfex
Drug: Fludarabine
40 mg/m^2 intravenously (IV) over 1 hour on days -6 through -2.
Other Name: 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 Name: Levetiracetam

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

Ages Eligible for Study:   up to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01666080

Contacts
Contact: Weston P. Miller, M.D. 612-625-2508 mill4991@umn.edu
Contact: Teresa Kvisto, RN 612-273-2924 tkivis1@fairview.org

Locations
United States, Minnesota
Masonic Cancer Center, University of Minnesota Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Weston P. Miller, M.D.    612-626-2778    mill4991@umn.eud   
Principal Investigator: Weston P. Miller, M.D.         
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Weston P. Miller, M.D. Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT01666080     History of Changes
Other Study ID Numbers: 2012OC065, MT2012-11C
Study First Received: July 31, 2012
Last Updated: May 15, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:
second stem cell transplant
donor hematopoietic engraftment
hematopoietic stem cell transplantation
inherited metabolic disorder

Additional relevant MeSH terms:
Hematologic Diseases
Hemoglobinopathies
Immunologic Deficiency Syndromes
Genetic Diseases, Inborn
Immune System Diseases
Busulfan
Fludarabine phosphate
Fludarabine
Etiracetam
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Alkylating
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists
Anticonvulsants
Central Nervous System Agents
Nootropic Agents
Antimetabolites, Antineoplastic
Antimetabolites

ClinicalTrials.gov processed this record on August 19, 2014