Allogeneic Transplantation For Severe Osteopetrosis

Phase 2

Completed

Conditions: Severe Osteopetrosis

Interventions: Procedure: umbilical cord blood transplantation
Drug: Campath-1H
Radiation: Total Lymphoid Irradiation
Drug: Busulfan
Drug: Cyclophosphamide
Drug: Fludarabine monophosphate
Procedure: marrow graft transplantation

Registration Number: NCT00775931

Lead Sponsor: Masonic Cancer Center, University of Minnesota

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 7

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
cord blood transplant conditioning	umbilical cord blood transplantation	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.
marrow graft transplant conditioning	Campath-1H	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.
marrow graft transplant conditioning	Total Lymphoid Irradiation	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.
marrow graft transplant conditioning	Fludarabine monophosphate	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.
cord blood transplant conditioning	Campath-1H	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.
marrow graft transplant conditioning	marrow graft transplantation	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.
marrow graft transplant conditioning	Busulfan	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.
cord blood transplant conditioning	Cyclophosphamide	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.
cord blood transplant conditioning	Busulfan	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.

Primary Outcome Measures

Name	Time	Method
Number of Patients Who Achieved Donor Cell Engraftment	Day 100

Secondary Outcome Measures

Name	Time	Method
Incidence of Grade II - IV Acute Graft-versus-host Disease	by Day 100 after transplant
Transplant Related Mortality at 100 Days	day 100
Transplant Related Toxicity	Day 100 post transplant