Text Size

Reduced Intensity AlloTransplant For Osteopetrosis

This study has been terminated.
(Excess toxicity)
Sponsor:
Information provided by:
Masonic Cancer Center, University of Minnesota
ClinicalTrials.gov Identifier:
NCT00638820
First received: March 11, 2008
Last updated: February 22, 2011
Last verified: February 2011
History of Changes
  Purpose

We believe that hematopoietic stem cell transplantation (HSCT) will help subjects with Osteopetrosis generate functioning osteoclasts, and by so doing assist in the resolution of the abnormal bone architecture, and the anemia and bone marrow failure that is also characteristic of this disease. However, we have found in past studies that approximately 30% of Osteopetrosis patients do not engraft. Therefore, in this study, we plan to use a different combination 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. The purpose of this research is to find 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.


Condition Intervention Phase
Osteopetrosis
 Procedure: Stem Cell or Umbilical Cord Blood Transplantation
Drug: Campath, Busulfan, Clofarabine
Procedure: Total Lymphoid Irradiation
 Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Reduced Intensity Allogeneic Transplantation For Severe Osteopetrosis Incorporating A Second Cd34 Selected Graft

Resource links provided by NLM:

U.S. FDA Resources

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

Primary Outcome Measures:
  • Number of Patients Achieving Donor Cell Engraftment [ Time Frame: Day 100 ] [ Designated as safety issue: No ]
    Number of patients with persistent presence of donor-derived cells at Day 100


Secondary Outcome Measures:
  • Number of Patients With Transplant Related Death [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
    Number of participants died during study by Day 100 and reason for death was related to transplant.

  • Number of Patients With Transplant Related Toxicity [ Time Frame: Day 100 ] [ Designated as safety issue: Yes ]
    Number of patients experiencing adverse effects due to transplant categorized by body system using Common Terminology Criteria for Adverse Events coding from the National Cancer Institute, Version 3.0.

  • Differential Imaging and Biologic Evaluations [ Time Frame: Day 100, 6 months, 1, 2 and 5 years ] [ Designated as safety issue: No ]
    These outcome measures were not assessed due to early study termination.


Enrollment: 3
Study Start Date: September 2007
Study Completion Date: May 2008
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Intent-To-Treat
Patients enrolled and received study treatment.
 Procedure: Stem Cell or Umbilical Cord Blood Transplantation
Stem Cell (unrelated or matched related donor grafts (both peripheral blood and marrow) infusion on Day 0 and 42; Umbilical Cord Blood on Day 0 and 42
Other Name: Bone Marrow Transplant
Drug: Campath, Busulfan, Clofarabine
  • 12 Campath-1H 0.3 mg/kg intravenously (IV) over 2 hours
  • 11 Campath-1H 0.3 mg/kg intravenously over 2 hours
  • 10 Campath-1H 0.3 mg/kg intravenously over 2 hours
  • 9 Busulfan <12 kg: 2.2 mg/kg/dose IV every 12 hours >12 kg: 1.6 mg/kg/dose IV every 12 hours
  • 8 Busulfan <12 kg: 2.2 mg/kg/dose IV every 12 hours >12 kg: 1.6 mg/kg/dose IV every 12 hours
  • 7 "Rest"
  • 6 Clofarabine 40 mg/m2 intravenously over 2 hours
  • 5 Clofarabine 40 mg/m2 intravenously over 2 hours
  • 4 Clofarabine 40 mg/m2 intravenously over 2 hours
  • 3 Clofarabine 40 mg/m2 intravenously over 2 hours
  • 2 Clofarabine 40 mg/m2 intravenously over 2 hours
Other Name: Busulfex, Clolar,Alemtuzumab
Procedure: Total Lymphoid Irradiation
Dose 500 cGy via anteroposterior (AP) and posteroanterior (PA) fields (250 cGy AP and 250 cGy PA).
Other Name: Therapuetic radation, radiation therapy

Detailed Description:

This transplant protocol will test the following: 1) the ability to achieve engraftment with the reduced intensity protocol, 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, Campath levels just prior to the administration of the graft, and establishment of mesenchymal stem cell lines. 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 <45 years of age, and will be diagnosed with severe osteopetrosis. This will be defined as having the following manifestations of the disease.
  • Bones that are uniformly markedly dense based on skeletal survey
  • No history that would suggest autosomal dominant inheritance
  • 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 substantially 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00638820

Locations
United States, Minnesota
University of MInnesota, Fairview
Minneapolis, Minnesota, United States, 55455
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: Paul Orchard, M.D., University of Minnesota
ClinicalTrials.gov Identifier: NCT00638820     History of Changes
Other Study ID Numbers: 0704M06581, MT2007-06
Study First Received: March 11, 2008
Results First Received: August 26, 2009
Last Updated: February 22, 2011
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
Busulfan
Clofarabine
Alemtuzumab
Immunosuppressive Agents
 Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Therapeutic Uses
Myeloablative Agonists

ClinicalTrials.gov processed this record on May 21, 2013