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Reduced Intensity AlloTransplant For Osteopetrosis

Primary Purpose

Osteopetrosis

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Stem Cell or Umbilical Cord Blood Transplantation
Campath, Busulfan, Clofarabine
Total Lymphoid Irradiation
Sponsored by
Masonic Cancer Center, University of Minnesota
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Osteopetrosis focused on measuring osteopetrosis

Eligibility Criteria

undefined - 45 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • University of MInnesota, Fairview

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intent-To-Treat

Arm Description

Patients enrolled and received study treatment.

Outcomes

Primary Outcome Measures

Number of Patients Achieving Donor Cell Engraftment
Number of patients with persistent presence of donor-derived cells at Day 100

Secondary Outcome Measures

Number of Patients With Transplant Related Death
Number of participants died during study by Day 100 and reason for death was related to transplant.
Number of Patients With Transplant Related Toxicity
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
These outcome measures were not assessed due to early study termination.

Full Information

First Posted
March 11, 2008
Last Updated
December 3, 2017
Sponsor
Masonic Cancer Center, University of Minnesota
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1. Study Identification

Unique Protocol Identification Number
NCT00638820
Brief Title
Reduced Intensity AlloTransplant For Osteopetrosis
Official Title
Reduced Intensity Allogeneic Transplantation For Severe Osteopetrosis Incorporating A Second Cd34 Selected Graft
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Terminated
Why Stopped
Excess toxicity
Study Start Date
September 2007 (undefined)
Primary Completion Date
May 2008 (Actual)
Study Completion Date
May 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Masonic Cancer Center, University of Minnesota

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteopetrosis
Keywords
osteopetrosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
3 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Intent-To-Treat
Arm Type
Experimental
Arm Description
Patients enrolled and received study treatment.
Intervention Type
Procedure
Intervention Name(s)
Stem Cell or Umbilical Cord Blood Transplantation
Other Intervention Name(s)
Bone Marrow Transplant
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Campath, Busulfan, Clofarabine
Other Intervention Name(s)
Busulfex, Clolar,Alemtuzumab
Intervention Description
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
Intervention Type
Procedure
Intervention Name(s)
Total Lymphoid Irradiation
Other Intervention Name(s)
Therapuetic radation, radiation therapy
Intervention Description
Dose 500 cGy via anteroposterior (AP) and posteroanterior (PA) fields (250 cGy AP and 250 cGy PA).
Primary Outcome Measure Information:
Title
Number of Patients Achieving Donor Cell Engraftment
Description
Number of patients with persistent presence of donor-derived cells at Day 100
Time Frame
Day 100
Secondary Outcome Measure Information:
Title
Number of Patients With Transplant Related Death
Description
Number of participants died during study by Day 100 and reason for death was related to transplant.
Time Frame
Day 100
Title
Number of Patients With Transplant Related Toxicity
Description
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.
Time Frame
Day 100
Title
Differential Imaging and Biologic Evaluations
Description
These outcome measures were not assessed due to early study termination.
Time Frame
Day 100, 6 months, 1, 2 and 5 years

10. Eligibility

Sex
All
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul Orchard, MD
Organizational Affiliation
Masonic Cancer Center, University of Minnesota
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of MInnesota, Fairview
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States

12. IPD Sharing Statement

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Reduced Intensity AlloTransplant For Osteopetrosis

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