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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT01666080
Recruitment Status : Recruiting
First Posted : August 16, 2012
Last Update Posted : November 3, 2022
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota

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 Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : August 2012
Estimated Primary Completion Date : June 2023
Estimated Study Completion Date : June 2023

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
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

Primary Outcome Measures :
  1. Time to Engraftment [ Time Frame: 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 :
  1. Incidence of Graft Failure [ Time Frame: 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.

  2. Status of Donor Chimerism [ Time Frame: 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.

  3. Incidence of Acute Graft-Versus-Host Disease (GVHD) [ Time Frame: Day 100 ]
    Acute Graft-Versus-Host Disease is a severe short-term complication created by infusion of donor cells into a foreign host.

  4. Change in Incidence of Chronic Graft-Versus-Host Disease (GVHD) [ Time Frame: 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.

  5. Incidence of Transplant Related Mortality [ Time Frame: 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.

  6. Incidence of Overall Survival [ Time Frame: 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.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   up to 55 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01666080

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Contact: Troy Lund, M.D., Ph.D. 612-625-2508
Contact: Paul Orchard, M.D. 612-626-2313

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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
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Principal Investigator: Troy Lund, M.D., Ph.D. Masonic Cancer Center, University of Minnesota
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Responsible Party: Masonic Cancer Center, University of Minnesota Identifier: NCT01666080    
Other Study ID Numbers: 2012OC065
MT2012-11C ( Other Identifier: Blood and Marrow Transplantation Program )
First Posted: August 16, 2012    Key Record Dates
Last Update Posted: November 3, 2022
Last Verified: November 2022
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:
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Hematologic Diseases
Genetic Diseases, Inborn
Antineoplastic Agents
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Alkylating Agents
Antineoplastic Agents, Alkylating
Myeloablative Agonists
Nootropic Agents