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
  Purpose

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.


Condition Intervention Phase
Severe Osteopetrosis
Procedure: umbilical cord blood transplantation
Drug: Campath-1H
Radiation: Total Lymphoid Irradiation
Drug: Cyclophosphamide
Drug: Busulfan
Drug: Fludarabine monophosphate
Procedure: marrow graft transplantation
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Allogeneic Hematopoietic Stem Cell Transplantation For Severe Osteopetrosis

Resource links provided by NLM:


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

Primary Outcome Measures:
  • Estimate the rate of donor engraftment for patients treated by hematopoietic stem cell transplantation [ Time Frame: Day 100 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 23
Study Start Date: August 2008
Estimated Study Completion Date: October 2015
Estimated Primary Completion Date: October 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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: 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: 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.
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
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   up to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  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: NCT00775931

Contacts
Contact: Paul Orchard, MD 612-626-1926 orcha001@umn.edu
Contact: Teresa Kivisto, RN 612-273-2800 tkivist1@fairview.org

Locations
United States, Minnesota
University of MInnesota, Fairview Recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Patricia Kleinke, RN    612-273-0857    pkleink1@fairview.org   
Contact: Cyndie Hibbs    612-625-8542      
Sponsors and Collaborators
Masonic Cancer Center, University of Minnesota
Investigators
Principal Investigator: Paul Orchard, MD Masonic Cancer Center, University of Minnesota
  More Information

No publications provided

Responsible Party: Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier: NCT00775931     History of Changes
Other Study ID Numbers: MT2008-20, 0808M42261
Study First Received: October 16, 2008
Last Updated: July 8, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Masonic Cancer Center, University of Minnesota:
osteopetrosis

Additional relevant MeSH terms:
Osteopetrosis
Osteosclerosis
Osteochondrodysplasias
Bone Diseases, Developmental
Bone Diseases
Musculoskeletal Diseases
Cyclophosphamide
Busulfan
Fludarabine phosphate
Fludarabine
Alemtuzumab
Vidarabine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on October 19, 2014