Allogeneic Transplantation For Severe Osteopetrosis

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Masonic Cancer Center, University of Minnesota
Sponsor:
Information provided by (Responsible Party):
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00775931
First received: October 16, 2008
Last updated: July 8, 2014
Last verified: July 2014

October 16, 2008
July 8, 2014
August 2008
October 2015   (final data collection date for primary outcome measure)
Estimate the rate of donor engraftment for patients treated by hematopoietic stem cell transplantation [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
the ability to achieve engraftment with the reduced intensity protocol and a second infusion of stem cells on day 42 [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00775931 on ClinicalTrials.gov Archive Site
  • Estimate Peri-transplant mortality (deaths) [ Time Frame: day 100 ] [ Designated as safety issue: Yes ]
  • Transplant related toxicity [ Time Frame: Day 100 post transplant ] [ Designated as safety issue: Yes ]
  • Graft-versus-host disease (incidence and severity) [ Time Frame: after transplantation ] [ Designated as safety issue: Yes ]
  • Tolerance of Campath-1H administration [ Time Frame: During study ] [ Designated as safety issue: Yes ]
  • Clinical Disease Monitoring [ Time Frame: post transplant ] [ Designated as safety issue: No ]
  • the mortality associated with transplant [ Time Frame: day 100 ] [ Designated as safety issue: Yes ]
  • patient outcomes, based on differential imaging and biologic evaluations prior to transplantation and at designated points after transplantation [ Time Frame: day 100, 6 months, 1, 2 and 5 years ] [ Designated as safety issue: No ]
Not Provided
Not Provided
 
Allogeneic Transplantation For Severe Osteopetrosis
Allogeneic Hematopoietic Stem Cell Transplantation For Severe Osteopetrosis

The purpose of this research is to explore what we believe may be a safer and more effective means of performing stem cell transplantation in patients with Osteopetrosis, using chemotherapy and radiation designed to bring about engraftment and lessen transplant mortality. Prior multi-institutional data in past studies found that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we utilize a reduced intensity design of pre-transplant drugs to try to make transplants safer for this disease, as well as to provide a second infusion of stem cells in patients with matched related or unrelated donors.

This revised transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol and a second infusion of stem cells on day 42, 2) the mortality associated with transplant by day 100, 3) patient outcomes, based on differential imaging and biologic evaluations prior to transplantation and at designated points after transplantation (day 100, 6 months, 1, 2 and 5 years). Additional biologic studies will include microarray analysis, and evaluation of blood parameters and genes that may be important in the disease process. In older patients, studies to evaluation osteoclast differentiation and function will also be offered.

Interventional
Phase 2
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Severe Osteopetrosis
  • Procedure: umbilical cord blood transplantation
    Umbilical cord blood will be collected, processed and shipped according to existing protocols. 2 cord blood units will be utilized if available. The choice of units will be based on the HLA typing standards of the University of Minnesota Blood and Marrow Program. If 2 units are not available, a single unit may be used. If a single unit is used, the unit should provide at least 10 x 107 nucleated cells/kg recipient body weight.
    Other Name: UCBT
  • Drug: Campath-1H
    Campath-1H will be administered 0.3 mg/kg subcutaneously per day for three days starting on Day -21 through Day -19.
    Other Name: Alemtuzumab
  • Radiation: Total Lymphoid Irradiation
    Dose 500 cGy via anteroposterior (AP) and posteroanterior(PA) fields (250 cGy AP and 250 cGy PA).
    Other Name: TLI
  • Drug: Cyclophosphamide
    Cyclophosphamide (50 mg/kg/dose) will be given IV on day -4, -3, -2 and -1 over 2 hours. The total dose to be given over 4 days is 200 mg/kg for cord blood grafts-receiving patients only.
    Other Name: Cytoxan
  • Drug: Busulfan
    patients<12 kg: 1.1 mg/kg/dose IV every 6 hours for 8 doses total; patients >12 kg: 0.8 mg/kg/dose IV every 6 hours for 8 doses. on Day -8 to -7 for donor grafts-receiving patients, and on Day -9 to -6 for cord blood grafts-receiving patients.
    Other Name: Busulfex
  • Drug: Fludarabine monophosphate
    Fludarabine (35 mg/m2 daily for 5 days, 175 mg/m2 total) will be administered IV over 30 minutes on days -6, -5, -4, -3, and -2 for donor grafts-receiving patients only.
    Other Name: Fludara
  • Procedure: marrow graft transplantation
    Related donor marrow will be collected, processed and shipped according to existing protocols of the National Marrow Donor Program or other URD registry, with the goal of achieving a cell dose of ≥ 6.0 x 108 nucleated cells/kg. The proportion of cells that are CD34+ will be determined prior to the administration of the graft. This will allow a portion of the graft (2 x 106 CD34+ cells) to be frozen for a subsequent infusion on day +42.
    Other Name: HSCT
  • Active Comparator: marrow graft transplant conditioning
    Pre-transplant conditioning using Campath-1H, Busulfan, Fludarabine monophosphate, and total lymphoid irradiation followed by unrelated or matched related donor marrow graft transplantation (both peripheral blood and marrow) and a second CD34 cell infusion on Day 42.
    Interventions:
    • Drug: Campath-1H
    • Radiation: Total Lymphoid Irradiation
    • Drug: Busulfan
    • Drug: Fludarabine monophosphate
    • Procedure: marrow graft transplantation
  • Active Comparator: cord blood transplant conditioning
    Pre-transplant conditioning using Campath-1H, Busulfan and Cyclophosphamide followed by unrelated umbilical cord blood transplantation and a second smaller portion cord blood graft infusion on Day 42.
    Interventions:
    • Procedure: umbilical cord blood transplantation
    • Drug: Campath-1H
    • Drug: Cyclophosphamide
    • Drug: Busulfan
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
23
October 2015
October 2015   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Patients eligible for transplantation under this protocol will be < or = 45 years of age, and will be diagnosed with severe osteopetrosis. This will be defined as having the following manifestations of the disease.

    1. Bones that are uniformly markedly dense based on skeletal survey
    2. No history that would suggest autosomal dominant inheritance
    3. Evidence of hematologic changes that are attributed to the underlying disease, including
  • the need for ongoing transfusions, OR
  • the presence of progressive anemia or thrombocytopenia, OR
  • a white blood cell differential with a predominance of immature forms and evidence of extramedullary hematopoiesis, OR
  • persistence of serious infectious complications that are thought to be due to the abnormal architecture of the bone that are resistant to surgical and medical interventions.

Exclusion Criteria:

  • Patients >45 years of age
  • Evidence of hepatic failure
  • Pulmonary dysfunction sufficient to significantly increase the risk of transplant.
  • Renal dysfunction with glomerular filtration rate (GFR) <30% of predicted.
  • Cardiac compromise sufficient to substantially increase the risk of transplantation
  • Severe, stable neurologic impairment.
  • Human immunodeficiency virus (HIV) positivity.
  • Pregnant or lactating females
Both
up to 45 Years
No
Contact: Paul Orchard, MD 612-626-1926 orcha001@umn.edu
Contact: Teresa Kivisto, RN 612-273-2800 tkivist1@fairview.org
United States
 
NCT00775931
MT2008-20, 0808M42261
Yes
Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
Not Provided
Principal Investigator: Paul Orchard, MD Masonic Cancer Center, University of Minnesota
Masonic Cancer Center, University of Minnesota
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP