Reduced Intensity AlloTransplant For Osteopetrosis

NCT ID: NCT00638820

Last Updated: 2017-12-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2
• Total Enrollment: 3 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-09-30
• Study Completion Date: 2008-05-31

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.

Conditions

Osteopetrosis

Keywords

osteopetrosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intent-To-Treat

Patients enrolled and received study treatment.

Group Type: EXPERIMENTAL

Stem Cell or Umbilical Cord Blood Transplantation

Intervention Type: PROCEDURE

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

Campath, Busulfan, Clofarabine

Intervention Type: DRUG

• 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

Total Lymphoid Irradiation

Intervention Type: PROCEDURE

Dose 500 cGy via anteroposterior (AP) and posteroanterior (PA) fields (250 cGy AP and 250 cGy PA).

Interventions

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

Intervention Type: PROCEDURE

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

Intervention Type: DRUG

Total Lymphoid Irradiation

Dose 500 cGy via anteroposterior (AP) and posteroanterior (PA) fields (250 cGy AP and 250 cGy PA).

Intervention Type: PROCEDURE

Other Intervention Names

Bone Marrow Transplant; Busulfex, Clolar,Alemtuzumab; Therapuetic radation, radiation therapy

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

• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Masonic Cancer Center, University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

University of Minnesota

Principal Investigators

Paul Orchard, MD

Role: PRINCIPAL_INVESTIGATOR

Masonic Cancer Center, University of Minnesota

Locations

University of MInnesota, Fairview

Minneapolis, Minnesota, United States

Countries

United States

Other Identifiers

MT2007-06

Identifier Type: OTHER

Identifier Source: secondary_id

0704M06581

Identifier Type: -

Identifier Source: org_study_id